Index to Anti-Aging Medicine
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M: Md - Mz
Mechanisms of Aging [Ben Best/Mechanisms of Aging, Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon], [99].
Mechanisms of Aging and Development [Elsevier/Mechanisms of Aging and Development, Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon] on-line. See Journals.
Mechanisms of Cellular Senescence [Index/Cellular Senescence, Index/Replicative Senescence, Index/Senescence, Index/Biomarkers of Cellular Senescence; Links, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension]. Also see Telomeres, Telomerase, hTERT, and Telomerase Activators.
Medical Diagnosis [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Medical Diagnostics, Video, Images, Papers, Patents, Books, LibCong, Amazon; Links/Expert Systems for Medical Diagnosis; Index/Medical Measurements; Links/Cardiovascular Diagnosis, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Cancer Diagnosis, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Neurological Diagnosis, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Pathogen Diagnosis, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Medical Diagnostic Instrumentation, Images, Video, Papers, Patents, Books, LibCong, Amazon]. See Aluminum Poisoning, Alzheimer's Disease, Arteriosclerosis, Arthritis, Atherosclerosis, Atherosclerotic Plaque, Autoimmune Disorders, Benign Prostatic Hyperplasia, Bone Cancer, Breast Cancer, Cancer, Colon Cancer, Cardiology, Cardiomyopathy, Cardiovascular Disease, Cataracts, Causes of Death, Cervical Cancer, Cognitive Decline, Death, Leading Causes of, Dementia, Dental Work (Dental), Diabetes, Endothelial Dysfunction, Epidermal Basal Cell Carcinoma, Esophageal Cancer, Eye Problems of Old Age, Geriatrics, Grey Hair (Hair Greying), Hair Loss, Heart Attack, Height Loss, High Blood Pressure, Histology of the Aging Brain, Histology of the Senescent Cells, Life Expectancies, Macular Degeneration, Mortality Charts, Purpura, Sarcopenia, Senescence, Senile Purpurea, Skin, Skin Cancer, Skin Lesions, Smoking and Aging, SNPs, Stiff Back, Stomach Cancer, Stroke, Surgery, Testicular Cancer, Tinnitis, Tumorigenesis, Urinary Tract Infections, Urology, Varicose Veins, Vascular Diseases, Virology, Wound Healing. See also Medical Measurements and Wikipedia/Medicine.
Medical Equipment [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Hospital Equipment, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Operating Room Equipment, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Medical Diagnostic Instrumentation, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Medical Information Systems, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Life Support Systems, Images, Video, Papers, Patents, Books, Amazon; Links/Hospital Life Support Systems, Images, Video, Papers, Patents, Books, Amazon; Links/Emergency Medicine Instrumentation, Images, Video, Papers, Patents, Books; Links/Medical Supplies, Images, Video, Papers, Books; Links/Hospitals, Links/Clinics, Links/Medical Offices].
Medical Illustration [Links, Images, Video, Papers, Books, LibCong, Amazon; Links/software for, Links/preparation of, Links/preparation of medical illustrations from medical images].
Medical Imaging [MedImageLinks; Links, Video, Images, Papers, Patents, Books, Medical Image Processing by James A. Green, LibCong, Amazon; Links/software for, Links/alternative preparation of, Links/preparation of medical illustrations from medical images, Links/medical image data collections, Links/CAT scan technology, Links/CAT scan medical image libraries; Links/NMR medical imaging technology, Links/NMR medical image libraries; Links/MRI medical imaging technology, Links/MRI medical image libraries; Links/PET scan medical imaging technology, Links/PET scan medical image libraries, Links/SPECT scan medical imaging technology, Links/SPECT scan medical image libraries, Links/ULTRASOUND medical imaging technology, Links/ULTRASOUND medical image libraries].
Medical Measurements [Links/Medical Measurements, Images, Video, Papers, Patents, Books, Amazon; Index/Blood Tests, LifeExtension/Blood Tests, Links/Blood Tests, Images, Papers, Patents, Books, Amazon; Index/Medical Diagnosis]. See Alzheimers Disease, Analytical Chemistry, Anatomy and Physiology, Arteriosclerosis, Atherosclerosis, Bioavailability and Pharmacokinetics, Bioinformatics, Biopsy, Biomarkers of Aging, Biomarkers of Longevity, Biomarkers of Senescence, Blood Tests, Cancer, Cardiology, lifexlabs/Cellular Senescence Measurements, Cognitive Decline, Dementia, DNA Sequencing, Fluorescence Microscopy, Genomics, Hypertension, Instrumental Analysis, Kidney Disease, Lipid Peroxidation, Lipoprotein phospholipase A2 (Lp-PLA2), Pathology, Pathway Analysis, Protocols, Medical Equipment, Medical Imaging, Metaphase Spread, Single Nucleotide Polymorphisms, lifexlabs/Telomere Measurements and Virology.
Medical School [Wikipedia/Portal:Medicine, Links, Images, Video, Papers, Books, Amazon; Wikipedia/Medical School; PubMed, NIH, MedLine, WebMD, HealthLine, Access Medicine, Wiki/Medicine, Medical Diagnosis, The Merck Manuals, U.S. National Library of Medicine].
Medical Curriculum: [Links, Video, Papers, Books; Wikipedia/Medicine, Links, Video, Papers, Books, Amazon].
__Anesthesiology [Links, Images, Video, Papers, Patents, Books, Amazon;
_____Wikipedia; Links/Geriatric Anesthesiology].
__Anesthesia [Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia].
__Bones [Links, Images, Video, Papers, Books, Amazon; Wikipedia; Links/Human Skeleton].
__Bone Surgery [Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia].
__Broken Bones (Treatment) [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
____[Links/Casts, Images, Video, Books, Amazon; Wikipedia; Links/Cast Materials, Images].
____The Bones and How they may be Set [Images, Video, Books].
__Burn Wounds [Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia].
__Disease [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Emergency Medicine [Links, Images, Video, Books, Amazon; Wikipedia; Links/Trauma].
__Family Medicine [Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatrics].
__Fractures [Links, Images, Video, Books, Amazon; Wikipedia; Links/Hip Fractures].
__General Anesthesia [Links, Images, Video, Books, Amazon; Wikipedia].
__Gerontology [Main Essay, Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Gynecology [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Hematology [Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatric Hematology].
__Hematopathology [Links, Images, Video, Papers, Patents, Books, Amazon].
__Hospital Medicine [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Internal Medicine
____[Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatrics: Internal Medicine].
__Medical Oncology
____[Index/Cancer, Links, Images, Video, Books, Amazon; Wikipedia; Geriatric Oncology].
__Medical Imaging
____[Links, Images, Video, Papers, Books, Amazon; Wikipedia; Links/X-ray, Links/MRI].
__Medical Sign [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Microbiology [Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatric Infections].
__Molecular Diagnostics [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Molecular Medicine [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Neurology [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Neurosurgery
_____[Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatric Neurosurgery].
__Obstetrics and Gynecology [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Ophthalmology
____[Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatric Opthamology].
__Otolaryngology
____[Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatric Otolarygology].
__Pain Management [Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia].
__Pathology [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Pathophysiology [Links, Images, Video, Papers, Books, Amazon; Wikipedia].(Nursing)
__Pediatrics [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Plastic Surgery (Neck Rejuvenation, Refs11/III.)
____[Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Psychiatry [Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatric Psychiatry].
__Route of Administration [Wikipedia, Links, Images, Papers, Books, Amazon; LifeExtension].
__Shock (circulatory) [Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia].
__Surgery [Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatric Surgery].
__Surgical Instruments [Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia].
__Surgical Nursing [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Surgical Oncology [Index/Cancer, Links, Images, Video, Books, Amazon; Wikipedia].
__Surgical Procedures [Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia].
__Symptom [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Trauma Treatment [Links, Images, Video, Papers, Books, Amazon; Wikipedia].
__Urology [Links, Images, Video, Books, Amazon; Wikipedia; Links/Geriatric Urology].
__Venipuncture [Index, Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia].
__Wound Management [Index, Links, Images, Video, Papers, Books, Amazon; Wikipedia].
MnSOD Manganese and Mitochondrial Aging
The Geriatric Customer at the Outer Limits. Press for The War of the Worlds. (Photo: NASA/Sirtis Major Planum, Mars.)
Links/The Geriatric Customer & Purge Theory.
At The Outer Limits, R < 10.
Music: Fly Me to the Moon by Frank Sinatra,
Satisfaction by the Rolling Stones,
Santa Claus is Coming to Town.
Medical Topics [Wikipedia/Medicine, Links, Books, Amazon/Medicine; Wikipedia/List of health_topics]; Dental; Medicaid, Medicare, Internet Use "Good for the Brain", 1UpHealth, Longevity, Med Net, Disease, Diagnosis, Vein, MedLine+, Physician, Merck Manuals, PDR, Medical Dictionary, Merriam-Webster, Merck Online: Merck Manual of Medical Information, Merck Manual of Health and Aging, Geriatrics, Merck Manual of Diagnosis and Therapy, Cancer, Neuroimaging, Cardio Imaging, Video Microscopy, Medical Image Processing, Robotic Surgery, Image-Guided Surgery; Anti-Aging Medicine, Labs; WebMD, Emergency Med [Wiki/List of Medical Emergencies, Links, Books, Amazon], Disease Control & Prevention, Atrial Fibrillation [Books, Amazon], Wiki/Surgery [Wiki/List of Surgical Procedures, Links, Books, Amazon], Wiki/Surgical Nursing [Links, Books, Amazon], Video Jug/Health & Medicine, iMedix, VisualMED. Also see The Heart Scan Blog and
Human Development [Wikipedia, Links, Images, Video, Books, Amazon].
Medical Treatment [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon]. See Antibiotics, Anti-cancer diet and drugs, Atherosclerosis, Caloric Restriction, Cancer, Cardiovascular Disease, Cellular Senescence, Chemotherapy, Chronic Diseases of Old Age, Clinical Trials, Death, Causes of, Gene Therapy, Geriatric Dermatology, Heart Attack, Hypertension, Pneumonia, Stroke, Virology.
Medicinal Biochemistry [Bibliography, The Medicinal Biochemistry Page, Links/Medicinal Biochemistry, Images, Video, Papers, Patents, Books, Amazon]. See also
Supplement Science [SupplementScience.org, Index, Links, Images, Video, Papers, Books, Amazon]. Joseph Price Remington, Alfonso R. Gennaro, Remington's Pharmaceutical Sciences, 19th edition, Mack, 1995. Vassilis Mougios, Exercise Biochemistry, Human Kinetics, 2006. John H. Block & John M. Beale Jr., Wilson & Gisvolt's Textbook of Organic Medicinal and Pharmaceutical Chemistry, 12th edition, Wolters Kluwer, Lippencott Williams & Wilkins, 2011.
Medicinal Properties [Wikipedia, Links, Papers, Books] of medicines in pharmacology [Links, Papers, Books, Amazon, Wikipedia].
Medicinal Mushrooms [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon LifeExtension]. See Chaga, the Reishi Mushroom [Index], and Li Ching Yuen.
Medicinal Television
[Ben Casey (Links, Video, Man, Woman, Birth, Death, Infinity),
General Hospital (Links, Video),
Marcus Welby, MD (Links, Video),
Young Doctor Kildare (Links, Video),
Young Frankenstein (Links, Video)].
Mediterranean Diet [Wikipedia, Links, Images, Video, Papers, Patents, Books, LifeExtension]. A Mediterranean diet deflecting cardiovascular disease is high-fiber and focused around fruits, vegetables, olive oil, nuts, and fish, with reduced reliance on meat and refined carbohydrates, which lower neuroprotective HGH and promote glycation. The Mediterranean Diet results in higher levels of omega-3 fatty acids and lower levels of mammalian meat fats (triglycerides) leading to high LDL/HDL cholesterol ratios, high homocysteine levels, and atherosclerosis. Red wine may be included for resveratrol. See the French Paradox and Jeanne Calment, who exercised, drank red port wine, and took 5 pounds of chocolate per week, improving circulation in her brain with arginine from cocoa, which also provided more nitric oxide for endothelial defense.
Medium-Chain Triglycerides [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Medium Chain Triglycerides (MCTs) found in coconut oil or palm oil (See oils) are a special type of saturated fat that have shorter chains than other fats, containing about 8/9 the calories per gram of ordinary fats at 8 calories/gram. Medium Chain Triglyerides are not stored in fat cells, but are used as fuel by muscles, being broken down into ketones that can be used as fuel by other tissues. Consumption of medium-chain triglycerides can enhance metabolism and lipolysis, the removal of fat from fat cells. Furthermore, research indicates that Medium-Chain Triglycerides can boost protein utilization and benefit the immune system. - (after Muscle and Fitness Magazine).
Meiotic Chromosomes [Links/Meiosis, Images, Video, Papers, Patents, Books, Amazon; Links/Meiotic chromosomes, Images, Video, Papers, Patents, Books, Amazon]. Meiotic chromosomes of dividing cells are longer in human females than in males [David Kipling, The Telomere], perhaps predicting telomeric length differences in the matched alleles of human diploid mitotic cells [Images]. Also see
Mitotic Chromosomes [Links, Images, Video, Papers, Patents, Books, Amazon] and
Mitosis [Links, Images, Video, Papers, Patents, Books, Amazon].
Melancor Melancor Site to reverse greying of hair [Books, LifeExtension], [48]. Greying of hair Patents/hair color therapy, may be reversed with DHEA or similar substances. [74s]. See Hair Greying: [Index, Links, Books, LifeExtension], Melancor to reverse greying of hair, [48]. Oral admistration of small molecule telomerase activators such as astralagus extract can restore hair color by rejuvenating the stem cells that restore hair melanocytes, at a rejuvenation rate of about 9 years per year. I had better luck with transdermal administration of astragalus extract to hair follicles than with oral administration. See Telomere Remodeling with Cyclic Telomerase Activation.
Melanocytes [Wikipedia/Melanocyte, Links, Images, Video, Papers, Patents, Books]. Melanocytes color hair, and depletion of the melanocyte stem cell niche causes hair to turn white. See also Revage 670 Hair Rejuvenation Therapy [Links/Laser Hair Rejuvenation, Images, Video, Papers, Patents, Books; Links/Hair Rejuvenation, Images, Video, Papers, Patents, Books]. See Sarin KY, Artandi SE (2007), Aging, graying and loss of melanocyte stem cells, Stem Cell Review, 2007 Fall;3(3):212-7 and Sarin KY, Cheung P, Gilison D, Lee E, Tennen RI, Wang E, Artandi MK, Oro AE, Artandi SE, Conditional telomerase induction causes proliferation of hair follicle stem cells, Nature, 2005 Aug 18;436(7053):1048-52 See also Index/Hair Graying.
Melanocyte Stem Cells (Melanoblasts) [Links/Melanocyte Stem Cells, Images, Video, Papers, Books; Links/Melanoblasts, Images, Video, Papers, Books; Links/Telomerase Activation of Melanocyte Stem Cells, Images, Video, Papers, Books; ]. Hair greying is caused by a depletion of the melanoblast niche. Hair follicles [Images] progress through distinct cycles of proliferation and hair synthesis (anagen), regression (catagen), and quiescence (telogen). Conditional activation of TERT can initiate a new anagen cycle [Papers] by activating quiescent hair follicle stem cells [Papers] in the hair follicle bulge region [Images]. (after a paper by Steven E. Artandi, Kavita Sarin, and Peggie Cheung). See also Revage 670 Hair Rejuvenation Therapy [Links/Laser Hair Rejuvenation, Images, Video, Papers, Patents, Books; Links/Hair Rejuvenation, Images, Video, Papers, Patents, Books].
Melanocyte-Stimulating Hormone (alpha melanocyte-stimulating hormone) [Wikipedia/Melanocyte-stimulating hormone, Links, Images, Papers, Patents, Books, Antiaging Firewalls: More Research Insight on Gray Hair and Adult Stem Cell Reproduction; Index/Hair Greying]. "Vitamin D metabolites, retinoids (retinoid creams), melanocyte-stimulating hormone, forskolin, cholera toxin, isobutylmethylxanthine (effect), diacylglycerol analogues (effect), and UV irradiation all trigger melanogenesis (the production of melanin from melanocytes) and in turn, pigmentation." - Wikipedia/Melanocyte. Perhaps hair greying [Index, 74s, 74s/Greying of Hair] can be alleviated by tyrosine (required for melanin production), Vitamin D, and forskolin, along with astragalosides or astragaloside IV skin cream (Terraternal) to stimulate a hair follicle anagen cycle. Melanocyte-stimulating hormone may also help. See also Revage 670 Hair Rejuvenation Therapy [Links/Laser Hair Rejuvenation, Images, Video, Papers, Patents, Books; Links/Hair Rejuvenation, Images, Video, Papers, Patents, Books]. Tribulus [Index, Links, Images, Papers, Patents, Books] boosts melanocyte-stimulating hormone. See Yang L, Lu JW, An J, Jiang X. (2006), Effect of Tribulus terrestris extract on melanocyte-stimulating hormone expression in mouse hair follicles, PubMed.gov/17259119. [Links/Tribulus terrestris extract, Images, Papers, Patents, Books].
Melanin [Links/Melanin, Images, Video, Papers, Patents, Books, Amazon/Melanin, LEF]. See Melancor, Melanocytes, Melanocyte Stem Cells, Melanocyte-stimulating Hormone, and Hair Greying.
Melanoma [Links/Melanoma, Images, Video, coursework, Papers, Patents, Books, LifeExtension, LibCong; Cancer; Skin Cancer; Carcinogens; Sunburn; Anticancer Nutraceuticals; Apoptosis; Telomerase Inhibitors; Anticancer Telomerase Activators; Metastasis, NFkB, NFkB Inhibitors, Angiogenesis Inhibitors].
IL-2 (Interleukin-2, a telomerase activator) has been approved for treatment of malignant melanoma. Melanoma may arise from too much exposure to sunlight. See causes of melanoma, treatment of melanoma, metastasis of melanoma, and inhibiting metastasis of melanoma. "Wortmannin inhibits telomerase activity in human melanoma cells in a dose-dependent manner." (Cong, Wright, and Shay, 2002). Garlic extracts may be used as NF-kB inhibitors to prevent the growth and spread of melanoma. See Yang J, Richmond A (2001), Constitutive IkappaB kinase activity correlates with nuclear factor-kappa B activation in human melanoma cells, Cancer Research 61:4901-4909. Uffort DG, Grimm EA, Ellerhorst JA (2009), NF-kappaB mediates mitogen-activated protein kinase pathway-dependent iNOS expression in human melanoma, Journal of Investigative Dermatology 129: 148-154.
Melanoma Removal [Links, Images, Video, Papers, Patents, Books, Amazon, Amazon/Mole & Melanoma removal].
Melatonin (N-acetyl-5-methoxytryptamine) [Links/Melatonin and Aging, Images, Video, Papers, Patents, Books; Priory/Melatonin, Wikipedia/Melatonin, Links/Melatonin, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension, Terraternal, Ben Best, IAAS; Telomerase Inhibitors/Melatonin; [1]]. Melatonin, a highly efficient scavenger of the very reactive and toxic hydroxyl radical [Images], molecule, resets aging clock, protects DNA, regulates the sleep-wake cycle, [1]. Melatonin, taken at bedtime, is a hormone released by the pineal gland. Melatonin is a small-molecule telomerase inhibitor for cancer cells. Melatonin is a NFkB inhibitor and inhibits cancer metastasis. However, melatonin also activates the expression of Interleukin-2 (List), a telomerase activator. The interleukin-2 activation improves the resistance of the immune system to cold viruses. Applying melatonin topically to the skin fights free radicals, which provides photoprotection and supports skin healing. LEF recommends skin cream including melatonin, GABA (Gamma-aminobutyric acid), MSM (methylsulfonylmethane), vitamin C, vitamin E, and extracts of green tea, black tea, and red tea. - See Links/melatonin skin creams (Gary Goldfaden, MD and Robert Goldfaden, Getting your Beauty Sleep with Topical Melatonin, LifeExtension/topical melatonin, April 2010.) Melatonin increases cellular levels of the endogenous antioxidant enzyme glutathione peroxidase. Melatonin also increases HGH release. See Wolden-Hansen T, Mitton DR, McCants RL, et al. (2000) Daily melatonin adminstration to middle-aged rats suppresses body weight, intraabdominal adposity, and plasma leptin and insulin independent of food intake and total body fat, Endocrinology, 2000 Feb;14(2):487-97. Melatonin is useful in preventing age-related macular degeneration. See Yi C, Pan X, Yan H, Guo M, Pierpaoli W. (2005), Effects of melatonin in age-related macular degeneration, Annals of the New York Academy of Sciences, 2005 Dec;1057:384-92 and Claudia Kelley (2012), Beyond Sleep: 7 Ways Melatonin Attacks Aging Factors, Life Extension Magazine, Sept. 2012. The article points to effective results using melatonin at 20 mg/day dosages. Also see Stephen Fredericks (2013), Melatonin: The Brain Hormone [On Line], Life Extension Magazine, September 2013. Melatonin guards the brain against oxidative stress and neurodegeneration, inhibiting Alheimer's Disease and Parkinson's Disease at doses of 5-25 mg/day. The age-postponing effect of melatonin may be greatly enhanced by the co-administration of thyrotropin-releasing hormone (TRH) [Walter Pierpaoli, et al, 1999].
2-mercaptoethylamine [VRP/2-mercaptoethylamine, Links, Images, Video, Papers, Patents, Books].
2-mercaptoethylamine is a life extending antioxidant - Dr. Denham Harman [Images].
Membrane Hypothesis of Aging [IAAS/Membrane hypothesis of aging by Prof. Zs.-Nagy, Links, Images, Video, Papers, Patents, Books, LibCong, Links/Imre Zs.Nagy, LifeExtension/Membrane Hypothesis of Aging, (4), (13)]. The membrane hypothesis of aging features treatment of the aging cell membrane with DMAE (dimethlyaminoethanol), Centrophenoxine, or BCE-001 to rejuvenate the cell membrane's penetrability to potassium, restoring lower potassium concentration inside cell, restoring youthful cellular colloidal properties, enzyme activity, youthful transcription, and youthful levels of cellular protein turnover (4, 13). This tends to eliminate lipofuscin wastes [Patents/lipofuscin, Patents/ceroids]. (4). In muscle cells, the theory is somewhat different, and the membrane penetrability to the chlorine ion is important.
Membrane Integrity [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Supplements for aging cell membrane integrity [Papers, Patents, Books, LifeExtension] include:
(1) Beta carotene [Links, Images],
(2) Garlic [Links, Images],
(3) Ginger root extract [Links, Images],
(4) Ginseng [Links, Images],
(5) Selenium [Links, Images],
(6) Cod liver oil [Links, Images], and
(7) Flax seed oil [Links, Images].
"Nutrients that preserve membrane integrity improve cell-to-cell signaling and protect cellular DNA, improving brain cell and muscle function, inducing cancer cell death, protecting against atherosclerosis and slowing progression of cardiovascular disease, enhancing muscle health, and protecting liver cells". See Susan Machado (2012), Nutrient Cocktail Delays Aging and Extends Life Span, Life Extension Magazine, May 2012. To this we may add:
(8) Gamma tocopherol [Links, Images].
(9) Sesame Lignans [Links, Images];
__Sesame Seed Oil (contains both gamma tocopherol and sesame lignans)].
(10) Vitamin E [Links, Images].
There are many other supplements in this category. See also Lipid Peroxidation, Membrane Hypotheis of Aging, Lecithin (Phosphatidylcholine), and Phosphatidylserine.
Cellular Senescence as Membrane Communications Failure [Essay, Report, Refs 9, Refs 10]
Cell membrane communications fail in the aging cell when caveolin-1 is overexpressed, causing open caveolae flasks in the cell membrane to pinch off and move to the inside of the cell, cutting off membrane receptors inside the caveolae, making the cell insensitive to growth factors such as PDGF and EGF (found in colostrum) and establishing senescence growth arrest. Caveolin-1 (gene CAV1) overexpression also causes p53 and p21 to stop the cell cycle and halt DNA synthesis. Recovery from cellular senescence can be achieved by lowering the expression of caveolin-1 with cyclic AMP (one of several small-molecule caveolin-1 inhibitors) from forskolin or exercise, and by lowering FOXO transcription factor levels with Akt kinase from IGF-1 produced by exercise while taking creatine monohydrate, or with Akt kinase from insulin from, say, 3 grams of Fenugreek seed taken before bedtime half of the month after exercise, or insulin from Gymnema Sylvestre. Small molecule caveolin-1 inhibitors are perhaps most effective, as senescent cells somewhat resist stimulation with insulin.
Membrane and Lipofuscin Wastes Theory of Aging [Books/Membrane Theory of Aging; Links/Membrane detoxification; Images, Papers, Patents, Books; Index/Lipofuscin, Links/Lipofuscin Waste, Images, Video, Papers, Patents, Books], (4).
Memory Enhancing Nutraceuticals [Links/Memory Enhancing Nutraceuticals; Images, Papers, Patents, Books, Life Extension; Brain Deterioration (Age-Related); Neurodegenerative Disorders; 7-Keto DHEA, Acetyl L-Carnitine, alpha GPC, Alpha lipoic acid, Ashwagandha, Bacopa, Caloric Restriction, DHA, Exercise Ginkgo Biloba, HGH secretagogues, Magnesium, Magnesium L-Threonate, Nerve Growth Factor boosters, Phosphatidylserine, Phosphatidylcholine, Pregnenolone, Pycnogenol, Rhodiola rosea, Rosemary, Saffron, Soy, Vinpocetine, Vitamin K1]. Bacopa, 7-Keto DHEA, and vinpocetine supplements enhance memory. Vinpocetine plus ginkgo biloba speeds processing of short-term memory. Phosphatidylserine repairs mitochondrial membranes, so that phosphatidylserine reverses memory loss. Phosphatidylcholine also helps reverse memory loss. Both phosphatidylserine and phosphatidylcholine are present in soy. Pine bark extracts such as pycnogenol improve memory and learning in senescence-accelerated mice. Rhodiola rosea improves measures of mental performance, including associative thinking, short-term memory, calculation, concentration, and speed of audiovisual perception. Rosemary improves memory, probably by boosting Nerve Growth Factor. Essential oil of rosemary also improves memory and alertness. Ashwagandha can improve memory and memory formation. Nerve Growth Factor boosters such as acetyl L-carnitine enhance memory, including verbal episodic memory. Neuroprotective HGH secretagogues also enhance memory. DHA impoves memory. Exercise improves memory, as does caloric restriction [4]. Vitamin K1 improves verbal episodic memory [LEF News, Jan 2014: Health Aff (Millwood) 2013 Oct;32(10):1698-705]. Sage, sage extracts, and essential oil of sage improve memory [2]. In addition, saffron improves memory [Papers, Patents, Books], improves myelin sheath support, and also improves powers of concentration, although it is an aphrodisiac. Alpha lipoic acid, acetyl-L-carnitine, docosahexaenoic acid (DHA), phosphatidylserine (PS), and alpha glyceryl-phosphoryl-choline (alpha-GPC) work together to improve cognitive performance.
References
[1] Graham J. McDougall, Jr, Vonnette Austin-Wells, Teena Zimmarman (2005),
Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement [OnLine],
J Holist Nurs Dec 2005; 23(4): 415-433.
[2] Michael Downey (2015), Sage,
Life Extension Magazine Feb 2015. Index/Sage, LEFsearch(Sage), Links/Sage.
[3] Slutsky I, Abumaria N, Wu LJ, et al. (2010),
Enhancement of learning and memory by elevating brain magnesium, Neuron 2010 Jan 28;65(2):165-77.
[4] Witte AV, Fobker M, Gellner R, Knecht S, Floel A. (2009),
Caloric restriction improves memory in elderly humans,
Proc Natl Acad Sci U S A 2009 Jan 27;106(4):1255-60.
[5] Khalsa DS (1998),
Integrated medicine and the prevention and reversal of memory loss,
Altern Ther Health Med 1998 Nov;4(6):38-43.
[6] Vallee M, Mayo W, Le Moal M. (2001),
Role of pregnenolone, dehydroepiandrosterone and their sulfate esters on learning and memory in cognitive aging,
Brain Res Brain Res Rev 2001 Nov;37(1-3):301-12.
[7] Mayo W, Lemaire V, Malaterre J, et al. (2005),
Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus,
Neurobiol Aging 2005 Jan;26(1):103-14.
Mesenchymal Stem Cells (hMSCs) [Links/Mesenchymal Stem Cells; Images, Papers, Patents, Books; Links/Therapy with Mesenchymal Stem Cells; Images, Papers, Patents, Books; Links/Production of Mesenchymal Stem Cells; Images, Papers, Patents, Books; Stem Cells]. Mesenchymal-derived cells from which bone, cartilage, connective tissue, circulatory, and lymphatic system cells are obtained do not express hTR much. The mesenchymal stem cell differentiation potential is osteogenic, chondrogenic, and adipogenic. They are currently being applied to bone and cartilage disease, cancer, heart disease, gastointestinal disease, diabetes, autoimmunity and neurodegenerative diseases. See Nedime Serakinci, Stacey F Hoare, Moustapha Kassem, Stuart P Atkinson & W Nicol Keith (2006), Telomerase promoter reprogramming and interaction with general transcription factors in the human mesenchymal stem cell, Regenerative Medicine, Jan 2006, vol.1, No.1, pp 125-131 (Summary in Future Medicine). "It is shown that repression of hTERT expression in hMSCs (human Mesenchymal Stem Cells) is due to promoter-specific histone hypoacetylation coupled with low Pol II and TFIIB trafficking. This repression is overcome by treatment with Trichostatin A (TSA), an HDAC inhibitor, concomitant with increases in promoter-specific histone acetylation and increases in Pol II and TFIIB tracking. hTR expression is also increased in TSA-treated hMSCs, concomitant with changes in Pol II and TFIIB dynamics." It is probably true that hyperacetylation with sodium butyrate, sodium butyrate chicken feed, or L-carnitine (recently found to be an HDAC inhibitor) would produce equivilant results. Also see Gene Therapy, Induced Pluripotent Stem Cells (iPS cells), Kidney Disease, Nuclear Reprogramming, Plasmids, Pluripotent Stem Cells, Stem Cell Technology, Telomerase Activators (7), Tissue Engineering, Transfection, and Wound Healing.
Metal Ions [Links, Images, Papers, Patents, Books, LifeExtension, Amazon/Metal Ions and Aging] [89], (12). Beef is a rich source of dangerous iron and copper.
(1) Iron catalyzes Fenton-reactions, leading to lipid peroxidation, inflammation, dementia, and Alzheimer's Disease when iron is too prevalent. See Kathleen Anderson (2012), Excess Iron and Brain Degeneration: The Little-Known Link, Life Extension Magazine, March 2012. EGCG crosses the blood-brain barrier to chelate iron. Other supplements that chelate iron include carnosine, cranberry extracts, curcumin, lipoic acid, pomegranate extracts, quercetin, and milk thistle extract.
(2) Copper helps cancer to metastasize.
Copper is chelated by carnosine, curcumin, quercetin, and resveratrol.
(3) Calcium can cap atherosclerotic plaque and is a factor in arteriosclerosis. (Hardening of the arteries also occurs via glycation and cross-linking of proteins in endothelial cell walls).
Vitamin K2 promotes the expression of osteocalcin to return calcium to the bones.
Vinpocetine chelates calcium, reverses tumoral calcinosis in the kidneys.
(4) Aluminum can cause neurofibrulary tangles associated with Alzheimers Disease.
Aluminum can be chelated with curcumin.
Metal Ion chelation [Index/Metal Ions, Links/metal ion chelation, Images, Video, Papers, Patents, Books, Books2, LibCong, LifeExtension, Papers/metal ion chelation in medicine]:
"Carnosine has an ability to chelate prooxidative metals, such as copper, iron, zinc
___and toxic heavy metals (lead, mercury, cadmium, nickel)."
Cranberry extracts chelate iron. See ursolic acid.
Curcumin chelates iron and copper and also aluminum, increases ferritin expression.
EDTA is also used to chelate heavy metal toxins.
EGCG crosses the blood-brain barrier to chelate iron, defending against Alzheimer's [Ref].
Lipoic acid reduces free iron levels [Links], chelates iron in liposomes.
Modified Citrus Pectin [Links] chelates heavy metals (lead, arsenic, cadmium),
___improving their excretion in urine [Isaac Eliaz, et al, Phytotherapy Research, 2006].
NAC (N-acetyl cysteine) chelates mercury, arsenic, cadmium, and lead. [Ref]
Pomegranate extracts chelate iron.
Quercetin chelates iron and copper.
Resveratrol chelates copper only.
Silibinin from Milk Thistle Extract chelates iron in the liver.
Vinpocetine chelates calcium, reverses tumoral calcinosis in the kidneys.
Vitamin K2 returns calcium to bones by promoting the expression of osteocalcin.
Metabolic Syndrome & Insulin Resistance [LEF/Metabolic Syndrome & insulin resistance, obese man's disease; Links/metabolic syndrome, Images, Papers, Patents, Books, LifeExtension; Links/insulin resistance, Images, Papers, Patents, Books, LifeExtension; Images, Patents, Books, LibCong/Metabolic Syndrome, Amazon, LifeExtension].
Metallic Wastes & Mitochondrial Theory of Aging [Patents/mitochondrial theory of aging, Books/Mitochondrial Theory of Aging; Links/Metallic Wastes and Mitochondrial Aging, Images, Papers, Patents, Books, LifeExtension; LibCong/Mitochondrial Theory of Aging] (11).
Metalloproteinases See Matrix Metalloproteinases, above.
Metaphase Spread [Links, Images, Video, Papers, Patents, Books, Amazon; Wikipedia/Cytogenetics, Links, Images, Video, Papers, Patents, Books; Links/Metaphase Spread Kits, Images; Chromosome Analysis; Links/Chromosome analysis, Images, Papers, Patents, Books; Links/Chromosome Karyotyping, Images, Papers, Patents, Books; Links/Chromosome Banding, Images, Papers, Patents, Books; Links/Chromosome FISH, Images, Papers, Patents, Books]. This is an analysis of chromosomes arrested during metaphase [Images], when the chromosomes are highly condensed and are visible under a light microscope. Colchicine treatment may be used to arrest cells in metaphase [Links, Images, Papers, Books; Links/Colchicine]. Fluorescent In Situ Hybridization (FISH) [Wikipedia, Links, Books, Amazon] is sometimes applied to metaphase spreads to render telomeres, genes, or other DNA sequences visible. Then the intensity of light emitted by a telomeric spot is proportional to the telomere length. See Fluorescent In Situ Hybridization technique for measurement of telomere length [Images, Papers, Patents, Books, Amazon; Wikipedia/FISH; Wikipedia/Telomeres, Images]. See also [Links/FISH Telomere Measurement Technique on a Metaphase Spread, Images, Papers, Patents, Books; Shay-Wright Labs Metaphase Spread for Telomere-Centeromere FISH, Shay-Wright Laboratory Methods]. For supporting material on the human genome, see Index/Gene, Index/Human_Genome, HUGO Gene Families, and Bibliography/The Genome of Homo Sapiens and Index/Bioinformatics. For more on measuring telomere and telomerase properties, see Refs/7.11 Measuring Telomere Length, Index/Telomere Length Measurement, and Labs/Telomere Measurements.
Metastasis of Cancer [Links/cancer metastasis, Images, Video, Papers, Patents, Books, LifeExtension, Amazon; Links/treating cancer metastasis, Images, Papers, Patents, Books, LibCong/Metastasis of Cancer, Amazon, LifeExtension; Links/Cancer Metastasis Journals; Apoptosis, Telomerase Inhibitors; Anticancer Telomerase Activators; NFkB, NFkB Inhibitors, Angiogenesis Inhibitors]. Cancer cells secrete proteases [Images, Video, Papers, Patents, Books] attacking the extracellular matrix, allowing cancer cells to invade surrounding tissue. See protease inhibitors [Images, Video, Papers, Patents, Books] for metastasis therapeutics [Papers, Patents, Books, LifeExtension]. The transcription factor NF-kB often drives cancer metastasis, activating genes supporting metastasis, so that NF-kB inhibitors may be used to treat it. See David Hoffnung (2011), The Inflammatory Factor Underlying Most Cancers, Life Extension Magazine, November 2011. Genistein, for example, is an NF-kB inhibitor that is effective against cancer metastasis. See Pavese JM, Farmer RL, Bergan RC (2010), Inhibition of cancer cell invasion and metastasis by genistein, Cancer Metastasis Review 2010 September; 29(3):465-82. Cancer metastasis may also be treated using Modified Citrus Pectin (MCP) [Links/modified Citrus Pectin, Images, Papers, Patents, LifeExtension]. Ordinary citrus pectin from citrus also inhibits cancer metastasis to a lesser degree. Chelating copper (with quercetin, resveratrol, curcumin, or carnosine) also inhibits cancer metastasis, as copper promotes cancer metastasis. See Links/cancer metastasis inhibitors and Links/cancer metastasis promoters. Silibinin from milk thistle is effective against many malignancies, including those of the liver, colon, skin, and prostate, and inhibits cancer metastasis. Zerumbone in ginger is also an NF-kB inhibitor that is effective against cancer metastasis while promoting apoptosis. See also Mulabagal V, Subbaraju GV, Rao CV, et al. (2009), Withanolide sulfoxide from Ashwagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase, and tumor cell proliferation, Phytotherapy Research 2009 July; 23(7):987-92.
Circulating Tumor Cell Assays [Links/Circulating Tumor Cell Assays, Images, Video, Papers, Patents, Books, LifeExtension]. Circulating tumor cell (CTC) Assays to detect cancer cells in the blood have predictive power regarding cancer relapse and recovery probabilities in both prostate cancer and breast cancer. Lung cancer and colon cancer also feature metastasis problems and may find CTC assays applicable. Life Extension Magazine (April 2010, p.54) quotes measurements done in Spain regarding breast cancer CTC assays. Patients who had circulating tumor cells were 269% more likely the experience a relapse and had a 300% greater risk of death. In a prostate cancer study, men positive for CTC were 12 times as likely to experience prostate surgery failure as CTC negative patients. See also Circulating Tumor Cell molecular analysis [Links/Circulating Tumor Cell molecular analysis, Video, Images, Papers, Patents, Books], and flow cytometry in circulating tumor cell analysis [Links/Flow cytometry for circulating tumor cell assays, Images, Papers, Patents, Books; Video/Flow Cytometry, Links/Flow cytometry, Images, Papers, Books].
Metformin [RxList/Metformin, Links/Metformin, Images, Papers, Patents, Books; Links/Metformin as a cancer inhibitor, Images, Papers, Patents, Books; Links/Metformin side effects, Papers]. Metformin simulates caloric restriction, [65], [33s]. Caloric Restriction mimetics include resveratrol. Also see glucoregulatory agents, lipase inhibitors such as green tea or carnosic acid from rosemary or rosemary extract, and appetite suppressants such as pinolenic acid. Metformin reduces cancer death. See James Saftig (2012), Can a Diabetes Drug Prevent Cancer Death?, Life Extension Magazine, Feb 2012. Metformin acts to inhibit cancer by promoting AMPK, AMP-activated protein kinase, as does caloric restriction and exercise. AMPK can cut off the cellular energy pipeline, cause cancer cells to starve themselves until autophagy stops the cells. AMPK "lowers sugar output from the liver, increases glucose uptake from the blood, maintains insulin sensitivity, and ultimately lowers blood sugar." See Li D (2011), Metformin as an antitumor agent in cancer prevention and treatment, J Diabetes 2011 Feb 21.
Methionine in Foods [HcuSupport/Methionine in Foods, Links, Images, Papers, Patents, Books, LifeExtension, Amazon/Methionine and Methylation; Index/hTERT methylation; Index/Telomeric Chromatin]. ...Reducing methionine in food to 1/5 the usual amount increased rat lifetimes 30% (Ben Best, Protein Damage and Maintenance in Aging, from Mechanisms of Aging). Methionine in red meat and poultry produces toxic homocysteine, which starts atherosclerosis by attacking and cracking veinous walls. Homocysteine production is aggravated when detoxifying methylation of homocysteine fails due to aging, [69s]. Methionine has methylating effect on DNA as well as on homocysteine.
"Folate plays an essential role in one-carbon transfer involving remethylation of homocysteine to methionine, thereby insuring the provision of S-adenosylmethionine (SAM-e), the primary methyl group donor for most biological methylation reactions." - (Young-In Kim, 2005). All DNA methytransferases use SAMe as a methyl donor.
Methylation [Links/Methylation, Images, Papers, Patents, Books, LEF; Links/DNA Methylation, Images, Papers, Patents, Books, LEF; Links/The epigenome, Images, Papers, Patents, Books, LEF; Index/hTERT methylation; Index/Telomeric Chromatin; Index/Homocysteine; Index/Gene Silencing]. Methylation is important in many biological reactions, and is important in gene silencing. Many genes are methylated to turn them off in the course of growth and development after their role is over. The hTERT promoter, on the other hand, is partially enabled by methylation in some kinds of cancer cells. However, the region -150 bp to +150 bp around the transcription start site of hTERT is unmethylated when the hTERT promoter is active, and transcription from hTERT is controlled by this region. Thus we still associate methylation with transcriptional repression, with some exceptions. Epigenome methylation may be used to distinguish between native DNA and pathogen DNA in an organism as an aid to the immune system. The usual approach recommended by nutritonists to avoid obesity and diseases associated with methylation defects is to keep levels of methyl donors suitably high. Methylating chemicals and their foodstuffs include:
(1) folic acid [Vitamin B9] (nuts, sunflower seeds, baker's yeast, liver), a telomerase activator,
(2) methionine (sesame seeds, peppers, spinach, leafy vegetables, fish),
(3) vitamin B6 (other vegetables, whole grain products),
(4) choline (soy or soy products, veal, chicken, egg yolk),
(5) genistein (soy or soy products), a telomerase inhibitor,
(6) vitamin B12 (milk, shellfish, beef),
(7) S-adenosylmethionine (SAM-e, a supplement).
"Folate plays an essential role in one-carbon transfer involving remethylation of homocysteine to methionine, thereby insuring the provision of S-adenosylmethionine (SAM-e), the primary methyl group donor for most biological methylation reactions." - (Young-In Kim, 2005). Homocysteine blockers incorporating folic acid and/or remethylating B-vitamins are important for endothelial defense against the acquisition of atherosclerotic plaque and the development of atherosclerosis, with its consequent heart attacks and ischemic strokes. See Index/Endothelial Dysfunction.
Demethylation of DNA
Demethylation of DNA counteracts gene silencing due to methylation. Vitamin C demethyates DNA at the CpG shores of CpG islands in embryonic stem cells and in fibroblasts, where it acts to accelerate the reprogramming of fibroblasts into induced pluripotent stem cells. There are some indications that demethylation improves telomere lengthening. In some kinds of cancer cells, methylation can act to improve transcription of hTERT. The hTERT promoter is normally demethylated to support hTERT transcription. Vitamin C may be useful in improving telomere lengthening in normal cells such as fibroblasts, and is certainly useful in retarding telomere shortening. See hTERT methylation. See also Tung-Liang Chung, Romulo M. Brena, Gabriel Kolle, Sean M. Grimmond, Benjamin P. Berman, Peter W. Laird, Martin F. Pera, and Ernst Jurgen Wolvetang (2010), Vitamin C Promotes Widespread Yet Specific DNA Demethylation of the Epigenome in Human Embryonic Stem Cells, Stem Cells, 26 OCT 2010, DOI: 10.1002/stem.493.
Microbiology [Wikipedia, Links, Images, Video, Papers, Books, LibCong, Amazon].
Microglial activation [Links, Images, Papers, Patents, Books, LibCong, LifeExtension]. Microglial activation is associated with increased production of IL-6 and TNF-alpha in the brain's microglial cells [Images], and may be triggered by amyloids, although microglial activation can occur in the absence of amyloid. Vitamin E suppression of microglial activation is neuroprotective [Links/suppressing microglial activation, Images, Papers, Patents, Books, LifeExtension]. See Index/Vitamin E and Index/Alzheimer's Disease.
Microglial Senescence [Links, Images, Papers, Patents, Books, LifeExtension].
Microglial senescence causes clean-up operations in the brain to fail, leading to amyloid beta accumulation and Alzheimer's Disease.
Microglia in the Aging Brain [Links, Images, Papers, Patents, Books, LibCong/Microglia in the aging brain, LifeExtension, Amazon; Links/Microglial cells, Images, Papers, Patents, Books, LifeExtension]. Microglia in the aging brain will be stopped by replicative senescence. See treatments: [77s]. Microglial rejuvenation via telomere remodeling with cyclic telomerase activation using astragalus extract or astragalosides such as astragaloside IV looks quite promising. The telomerase activator Nitric Oxide from arginine and/or citruilline is also beneficial in preventing microglial senescence [Papers, Patents, Books, LifeExtension]. Antioxidants such as vitamin C and Vitamin E are also promising as telomerase inducers for inhibiting microglial senescence. Microglia are derived from hematopoietic stem cells, so telomerase activators acting on hematopoietic stem cells should be effective in supplying long-telomere microglial cells. This would probably include HIF-1, for instance. See John Schloendorn, Sebastian Sethe, and Alexandra Stolzing (2007), Cellular Therapy Using Microglial Cells, Rejuvenation Research March 2007, 10(1): 87-100. Microglial precursors can cross the blood–brain barrier and to home in on sites of neural damage and inflammation.
Micronutrients [Linus Pauling Institute/Micronutrients, Patents/Micronutrients and Aging, Ben Best, Links, Papers, Patents, Books, LibCong, LifeExtension] [55].
MicroRNA (miRNA) [Wikipedia/MicroRNA, Links/miRNA in anti-aging, Books; Links/MicroRNA, Images, Video, Papers, Patents, Books, LibCong/Microglia in the aging brain, LifeExtension/microRNA, Amazon]. "MicroRNAs, or miRNAs, are increasingly being accepted as playing a crucial regulatory role in normal and dysfunctional cellular processes. They represent a class of small, noncoding RNA molecules, which have been shown to be involved in almost every human pathology currently under study. From tumor progression and viral host interactions, to immune response and stem cell fate determination, miRNAs are quickly growing in importance as the "master regulators" in cell cycle processes." - Webinar on miRNAs. Of course, the hTR RNA component of telomerase seems to be an example of miRNA. However,it is NOT. MiRNAs are 21-23 nucleotides in length and regulate gene expression. See [Links/MicroRNA in hTERT regulation, Images, Papers, Patents, Books; Links/MicroRNA in hTERC regulation, Images, Papers, Patents, Books; Links/MicroRNA in gene regulation, Images, Papers, Patents, Books]. MicroRNAs were discovered in 1993 by Lee and colleagues in the Victor Ambros Lab, although the term "microRNA" was not introduced until 2001. Note siRNA (small interfering RNA) also exists. See [Links/SiRNA in anti-aging; Wikipedia/SiRNA, Links/SiRNA, Images, Video, Papers, Patents, Books, LifeExtension/SiRNA]. SiRNAs are "a class of double-stranded RNA molecules, 20-25 nucleotides in length, that play a variety of roles in biology. Most notably, siRNA is involved in the RNA interference (RNAi) pathway, where it interferes with the expression of a specific gene." SiRNA was not discovered until 1999.
Microscopy [Nikon Microscopy U, Wikipedia/Microscopy, Links/microscopy, Images, Video, Papers, Patents, Books, LibCong/Microglia in the aging brain, Amazon].
Milk [Wikipedia/Milk, Links/Milk, Images, Video, Papers, Patents, Books, Amazon]. Cow's milk is 87% water and 13% solids. The protein fraction is 80% casein protein, 20% whey protein. In fact, the ratio of whey/casein = 20/80 in cow's milk, whereas whey/casein = 60/40 in human milk. Thus human milk has a ratio of whey protein to casein protein that is 3x higher than in cow's milk.
Milk Peptide Complex [Links, Images, Video, Papers, Patents, Books; Index/Wrinkles; Index/Skin]. According to research done at the Chemisches Labortorium of Dr. Kurt Richter in Berlin, Germany (Tel +49 (0)30 85 1026-0, info@clr-berlin.com), Milk Peptide Complex (MPCTM) is described as having regenerative properties when applied to the skin. Transforming Growth Factor beta [Images, Papers, Patents, Books] (TGF-beta) is one of these regenerative factors. The complex boosts collagen synthesis in the skin and the synthesis of other components of the extracellular matrix [Index]. Measurements show that it reduces wrinkle depths and skin roughness. It is also described as fighting cellulite by stimulating production of connective tissue components. (See MPCTM - The multifunctional cosmetic active, SOFW-Journal, 3-2009.) Interstingly, bovine colostrum [Index, Images] (early cow's milk), has regenerative properties based on its telomerase activators [Index], which include Epidermal Growth Factor and IGF-1 [Index]. Colostrum skin creams [Images] are sold.
Milk Thistle [Links/Milk Thistle, Images, Papers, Patents, Books, LifeExtension, LibCong; Index/Silymarin; Telomerase Activators/(102) Silymarin, Telomerase Activators/(146) Milk Thistle Extract, Links/Silybum marianum, Images; The Daisy Family (Asteraceae); Blessed Milk Thistle; Silymarin supplements, Milk Thistle Extract supplements]. Milk thistle is a member of the Daisy family (Asteraceae), is an anticancer telomerase inhibitor for cancer cells and can prevent the loss of glutathione, an endogenous antioxidant [Life Extension Magazine, July 2009]. "The seeds of milk thistle have been used by herbalists for 2000 years to treat chronic liver disease and protect the liver against toxins." - Wikipedia/Milk_Thistle. Many of these effects are due to milk thistle's silymarin (Telomerase Activator (102) Silymarin or (146) Milk Thistle Extract). Milk thistle's silybinin also protects against lung, prostate, skin, and colon cancer, and against cancer metastasis. See also Silymarin [Index], and Silybinin [Papers, Patents, Books, LifeExtension]. Active ingredients of milk thistle include: Silymarin and silybinin, with silybin A, silybin B, isosilybin A, isosilybin B, silydianin, isosilydianin, silychristin and isosilychristin. See Dhanalakshmi S, Singh RP, Agarwal C, Agarwal R (2002), Silibinin inhibits constitutive and TNFalpha-induced activation of NF-kappaB and sensitizes human prostate carcinoma DU145 cells to TNFalpha-induced apoptosis, Oncogene, 2002 March 7; 21(11):1759-67. Silibinin from milk thistle extract chelates iron in the liver. See Metal Ions. Note that phosphatidylcholine (lecithin) makes silibinin more bioavailable [Raegan Linton, 2014].
Milk thistle [Images] inhibits LDL oxidation and the consequent binding of monocytes to vascular walls and is useful in treating athersclerosis by inhibiting the formation of atherosclerotic plaque. See Wallace S, Vaughn K, Stewart BW, et al. (2008), Milk thistle extracts inhibit the oxidation of low-density lipoprotein (LDL) and subsequent scavenger receptor-dependent monocyte adhesion, Journal of Agricultural and Food Chemistry, June 2008, 56(11):3966-72. See Atherosclerosis.
Music[2]: HAL 9000 sings Daisy, from 2001: A Space Odyssey.
Minoxidil [Wikipedia, Links]. Trade name Rogaine [Links]. Used to treat baldness, but positive effects recede after stopping treatment [74s]. See Index/Hair Loss Treatment.
Mitochondrial Biogenesis [Links/Mitochondrial Biogenesis, Images, Video, Papers, Patents, Books, LifeExtension; Links/Promoting Mitochondrial Biogenesis, Images, Papers, Patents, Books, LifeExtension; Links/Mitochondrial Biogenesis with NO, Images, Video, Papers, Patents, Books, LibCong, Amazon/mitochondrial biogenesis, LibCong/Mitochondrial biogenesis, LifeExtension; Ben Best/Mitochondria and Aging]. See also NO More Heart Disease by Nobel Prize Winner Dr. Louis B. Ignarro, who recommends 5 grams of L-arginine per day with 250 mg to 1000 mg per day of L-citrulline with antioxidants including alpha lipoic acid to improve Nitric Oxide (NO) levels. PQQ promotes mitochondrial biogenesis [LEF, Links/Mitochondrial Biogenesis with PQQ, Images, Video, Papers, Patents, Books]. Mitochondrial biogenesis may be reliably sustained by caloric restriction or strenuous physical activity. (See Perry Marcone (2011), Generate Fresh Mitochondria with PQQ, Life Extension Magazine, February, 2011.) See Chowanadisai W, Bauerly KA, Tchaparian E, Wong A, Cortopassi GA, Rucker RB (2010), Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression, Journal of Biological Chemistry, 2010 Jan 1; 285(1):142-52. See also Karamanlidis G, Nascimben L, Couper GS, Shekar PS, del Monte F, Tian R (2010), Defective DNA replication impairs mitochondrial biogenesis in human failing hearts, Circulation Research 2010 May 14;106(9):1591-8. Also see Matthews RT, Yang L, Browne S, Baik M, Beal MF (1998), Coenzyme Q administration increases brain mitochondrial concentrations and exerts neuroprotective effects, Proceedings of the National Academy of Sciences USA 1998 July 21;95(15):8892-7.
Mitochondrial Biogenesis Improved by Branched-Chain Amino Acids [Links, Images, Papers, Patents, Books, LifeExtension]. Note that Mus-L Blast protein is an excellent source of leucine, isoleucine, and valine, the branched chain amino acids. See D'Antona G, Ragni M, Cardile A, et al. (2010), Branched chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle biogenesis in middle-aged mice, Cellular Metabolism, 2010 Oct 6; 12(4): 362-72. Also see Mitilde Parente, Can a Power Booster Also Be a Longevity Booster?, Life Extension Magazine, May 2011. Prior studies showed that branched-chain amino acids extended life span in yeast (Alvers, et al, 2009). BCAA-fed mice experienced a 12% increase in life span and a dose-dependent response for mitochondrial biogenesis, and exercise (9) was shown to further improve the consequent mitochondrial biogenesis.
AMPK Regulates Mitochondrial Biogenesis [Links, Papers, Patents, Books, LifeExtension].
Note that AMPK (AMP-activated protein kinase) regulates the formation of new mitochondria [1], [2]. Thus activation of AMPK by a host of AMPK-activating nutraceuticals promotes mitochondrial biogenesis.
References
[1] Salminen A, Kaarniranta K. (2012),
AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network,
Ageing Res Rev 2012 Apr;11(2):230-41.
[2] Reznick RM, Zong H, Li J, et al. (2007),
Aging-associated reductions in AMP-activated protein kinase activity and mitochondrial biogenesis,
Cell Metab 2007 Feb;5(2):151-6.
Mitochondrial Components [Ben Best/Mitochondria and Aging; UTMB/CellBio/Mitochondria, LifeExtension/mitochondria, LibCong/Mitochondria, Links/mitochondrial structure, Images; Books/mitochondria, Amazon/mitochondria; Anti-Aging_Firewalls/Mitochondrial Basics, Anti-Aging_Firewalls/Mitochondrial Stress], (1)
Mitochondrial hTERT [Links/Mitochondrial hTERT, Images, Papers, Patents, Books]. See the articles Zhang, P., Chan, S.L., Fu, W., Medoza, M., and Mattson, M.P. (2003), TERT suppresses apoptosis at a premitochondrial step by a mechanism requiring reverse transcriptase activity and 14-3-3 protein binding ability, FASEB Journal 17, 767-769. Haendeler, J. et al. (2004), Antioxidants inhibit nuclear export of telomerase reverse transcriptase and delay replicative senescence of endothelial cells, Circulation Research 94, 768-775. Santos, J.H., Meyer, J.N., Skorvaga, M., Annab, L.A., and Van Houten, B. (2004), Mitochondrial hTERT exacerbates free-radical mediated mtDNA damage, Aging Cell 3, 399-411. Santos, J.H., Meyer, J.N., and Van Houten, B. (2006), Mitochondrial localization of telomerase as a determinant for hydrogen peroxide-induced mitochondrial DNA damage and apoptosis, Human Molecular Genetics 15, 1757-1768. Massard, C., et al. (2006), hTERT: a novel endogenous inhibitor of the mitochondrial cell death pathway, Oncogene 27, 3754-3760. Lee, J., et al. (2008), TERT promotes cellular and organismal survival independently of telomerase activity, Oncogene 27, 3754-3760.
Haendeler J, Jakob S, Altschmied J, Goy C, Spyridopoulos I, Zeiher AM, Brandt U, Dimmeler S, et al., (2009), Mitochondrial telomerase reverse transcriptase [?] binds to and protects mitochondrial DNA and function from damage, Arteriosclerosis, Thrombosis, and Vascular Biology. (2009). "Mitochondrial TERT exerts a novel protective function by binding to mitochondrial DNA, increasing respiratory chain activity and protecting against oxidative stress-induced damage."
Mitochondrial Apoptosis
[Links, Images, Video, Papers, Patents, Books; Index/Apoptosis; Ben Best/Mitochondria and Aging].
Mitochondrial Dysfunction [Ben Best/Mitochondria and Aging, Links/Mitochondrial Dysfunction, Images, Video, Papers, Patents, Books, LifeExtension; Links/Mitochondrial Dysfunction and neurodegenerative disease, Images, Video, Papers, Patents, Books, LifeExtension; Links/Mitochondrial protective agents, Images, Video, Papers, Patents, Books, LifeExtension]. Compounds preferentially targeting mitochondria include metabolic antioxidants, mitochondria-directed antioxidants and Szeto–Schiller peptides. Also consider the novel action of the antihistamine drug Dimebon on mitochondria. See Paula I. Moreira, Xiongwei Zhu, Xinglong Wang, Hyoung-gon Lee, Akihiko Nunomura, Robert B. Petersen, George Perry, Mark A. Smith (2010), Mitochondria: A therapeutic target in neurodegeneration, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1802(1), January 2010, 212-220.
See also Logan Bronwell (2013), Carnitine Restores Cellular Function, Life Extension Magazine, March 2013. "Carnitine deficiency leads to wholesale destruction of mitochondria... Supplementing with carnitine can restore mitochondrial function to near-normal levels... The heart muscle uses fat as its primary energy source. Carnitine is a fat-transporting compound that is absolutely essential for normal heart function. Over time, the decline of carnitine plays a role in the weakening of the heart’s muscles."
(1) Acetyl L-carnitine [Images] crosses the blood-brain barrier, benefiting mitochondria in the brain. It is the main molecule responsible for moving fat across the mitochondrial membrane. Its extra acetyl molecule provides extra energy to brain cells. It is often sold with alpha lipoic acid, which also improves mitochondrial function.
(2) "Propionyl-L-carnitine [Images] is essential in carbohydrate and lipid metabolism and is a potent antioxidant."
(3) Glycine propionyl-L-carnitine [Images] is particularly effective in muscle tissue, and enhances exercise performance.
(4) L-Carnitine [Images] is synthesized from methionine (say from fish) and lysine in the presence of vitamin C.
(5) L-Carnitine L-tartrate [Images] enhances the density of testosterone receptors, and "has been shown to be absorbed faster than other L-carnitine compounds".
Mitochondrial dysfunction can often be reversed with antioxidant CoQ10 (300 mg/day), mitochondrial biogenesis-enhancing PQQ (20 mg/day), and shilajit (200 mg/day). Note that mitochondrial biogenesis may arise from sustained caloric restriction, strenuous physical activity, or PQQ. See Michael Downey (2013), Three-Step Strategy to Reverse Mitochondrial Aging [On-Line], Life Extension Magazine, August 2013. See also Long J, Gao F, Tong L, Cotman CW, Ames BN, Liu J. (2009), Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine, Neurochem Res 2009 Apr;34(4):755-63.
Mitochondrial Measurements [Links/Mitochondrial measurements, Images, Video, Papers, Patents, Books]. See Protocols, Mitochondrial. In the early 1990s "numerous laboratories reported that only very small quantities of mutant mtDNA were present even in very elderly individuals.... Studies showed, however, that free radical damage to mitochondria was correllated to life span.". - Aubrey D.N.J. de Grey, The Mitochondrial Free Radical Theory of Aging, 1999, pg.2. See Courtagen Clinical Mitochondrial Genetic Testing [Images, Video, Papers, Patents, Books, LifeExtension], clinical sequencing of mitochondrial DNA [Images, Video, Papers, Patents, Books, LifeExtension], and clinical sequencing of nuclear mitochondrial genes [Images, Video, Papers, Patents, Books, LifeExtension]. "About 1,100 proteins are known to reside in the mitochondria. Most of these are encoded by nuclear DNA". See the mitochondrial proteome and clinical analysis of the mitochondrial proteome. Also see GeneDx and their list of mitochondrial disorders.
Mitochondrial Membrane Potential [Links/Mitochondrial membrane potential, Images, Video, Papers, Patents, Books; Links/Mitochondrial membrane potential of senescent cells, Images, Video, Papers, Patents, Books; Ben Best/Mitochondria and Aging]. The mitochondrial membrane potential of senescent cells is reduced compared to the mitochondrial membrane potential of youthful cells. Attempts to restore senescent cells have succeeded with restoration of the mitochondrial membrane potential. See Choi HR, Cho KA, Kang HT, Lee JB, Kaeberlein M, Suh Y, Chung IK, Park SC (2011), Restoration of senescent human diploid fibroblasts by modulation of the extracellular matrix, Aging Cell, 2011 Feb;10(1):148-57.
Mitochondrially Targeted Anti-Senescence Drugs [Links/Mitochondrially targeted anti-senescence drugs, Images, Video, Papers, Patents, Books]. Endogenous antioxidants such as catalase and CoQ10 have been used successfully against free radicals produced by mitochondria. Plastoquinone derivatives from Vladimir Skulachev are a new development in this domain. See also Atamna H, Robinson C, Ingersoll R, Elliott H, Ames BN.(2001), N-t-Butyl hydroxylamine is an antioxidant that reverses age-related changes in mitochondria in vivo and in vitro, FASEB Journal 2001 Oct;15(12):2196-204. Astaxanthin inhibits both cell death and mitochondrial dysfunction, blocking the induction of apoptosis by caspase-3 [HUGO] and sharply lowering ROS. UCP3 may be upregulated by thyroid hormone T3, which may be obtained from thyroid hormone T4. The UPC3 gene's protein product is thought to protect mitochondria against lipid-induced oxidative stress. Thyroid hormone T4 may be upregulated by bacopa, then converted to thyroid hormone T3 by bauhiniastatins from bauhinia purpurea L. Thyroid hormone T3 may also be upregulated directly by 7-keto-DHEA to generate UCP3. Also see Pyrroloquinoline quinone (PQQ) for improving mitochondrial biogenesis. Other supplements useful for improving mitochondrial function include:
B-vitamins B1, B3, B6, B12, and folate, acetyl L-carnitine, alpha lipoic acid, CoQ10 (ubiquinol), ginger root extract, ginseng, and selenium. See Susan Machado (2012), Nutrient Cocktail Delays Aging and Extends Life Span, Life Extension Magazine, May 2012. "Mitochondrial-enhancing nutrients improve energy availability in many tissues, preventing fatty liver disease, promoting weight loss, and preventing obesity, improving cardiovascular and skeletal muscle function, improving cognition, and protecting brain cells from Parkinson's Disease." See also Logan Bronwell (2013), Carnitine Restores Cellular Function, Life Extension Magazine, March 2013. "Carnitine deficiency leads to wholesale destruction of mitochondria... The heart muscle uses fat as its primary energy source. Carnitine is a fat-transporting compound that is absolutely essential for normal heart function. Over time, the decline of carnitine plays a role in the weakening of the heart’s muscles." Carnitine is synthesized from lysine and methionine (say, from fish) in the presence of vitamin C. Propionyl-L-Carnitine at 1.5-6 grams/day is most useful for muscles, acetyl-L-carnitine is most useful for the brain. L-carnitine L-tartrate is also useful. Recently, it has been discovered that L-carnitine is an HDAC inhibitor that might be used to improve the transcription of hTERT and hTR in mesenchymal-derived tissues, which feature condensed chromatin, by hyperacetylating histones for chromatin expansion. See Long J, Gao F, Tong L, Cotman CW, Ames BN, Liu J. (2009), Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine, Neurochem Res 2009 Apr;34(4):755-63.
N-tert-butyl Hydroxylamine (NtBHA) is a spin-trap compound sold as a chemical causing a large increase in life span via its hydroxyl radical scavenging capability. See Atamna, et. al, (2001), N-tert-butyl hydroxylamine reverses age-related changes in mitochondria [PDF file], The Faseb Journal, 2001; 15:2196-2204.
Mitochondrial Theory of Aging [Links/Diseases impacted by mitochondrial dysfunction, The Mitochondrial Free Radical Theory of Aging by Aubrey De Grey, Landes Bioscience, 1999, Ben Best/Mitochondria and Aging, James South/Mitochondrial Theory of Aging, Innovita/Mitochondrial Theory of Aging and Disease, Amazon/Mitochondrial Theory of Aging, Links/Mitochondrial Theory of Aging, Images, Video, Papers, Patents, Books, LibCong, LifeExtension; Ben Best/Mitochondria and Aging], [50]. Antioxidants targeted for mitochondria have been devised by Aubrey de Grey (videos). Acetyl L-carnitine plus alpha lipoic acid is an effective treatment in mitochondrial aging. Acetyl-L-Carnitine plus Hydergine [Links] has also been recommended. In addition to acetyl L-carnitine with R-lipoic acid [Images] (contained in alpha lipoic acid), LEF also highly recommends CoQ10 in ubiquinol form with CoQ10-enhancing shilajit for mitochondrial defense. See treatment for mitochondrial aging [Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon]. A mitochondrial theory of aging was devised by Australian scientist Anthony Linnane in 1989. Linnane began by observing that mutations accumulate in mitochondrial DNA with age and finished by showing that less than 5% of the mitochondrial DNA from the muscle tissue of a 90 year old subject [Images] was intact. Antioxidant protection for mitochondria may be defeated by unchelated metallic ions, so that chelation of iron and copper, primarily from beef, are especially important for the mitochondrial theory of aging (12). R Alpha Lipoic Acid, quercetin, curcumin (in turmeric or curry powder) and carnosine chelate iron and copper, protecting mitochondria from the unchelated metallic ions. Resveratrol chelates copper only. Hippocampal mitochondrial damage is seen in laboratory animals quite independently of caloric intake if iron and copper are added to their diet. Lack of iron and copper chelation interferes with MnSOD in the mitochondria. By chelating iron and copper (India - curcumin in curry) or by avoiding iron and copper input (Japan - fish intensive), India and Japan enjoy lower rates of Alzheimer's Disease and Dementia stemming from mitochondrial damage. See also Hydergine. [Index, Links/Hydergine, Books, LifeExtension]. According to The Mitochondrial Theory of Aging (James South) hydergine is one of the most effective substances in combating mitochondrial aging in rats. Hydergine at 6-9 mg/day is believed safe for humans. Otherwise, consider the role in mitochondrial aging of Glutathione [Index, Books, LifeExtension]. "Glutathione (GSH) plays a key role in protecting mitochondria and mtDNA from oxidative damage. GSH protects against mtDNA-damaging lipid peroxidation in the inner mitochondrial membrane, where the ETC [Electron Transport Chain] is located. GSH (glutathione) also breaks down H2O2, another oxidant normally produced within mitochondria and which damages mtDNA. Unfortunately, "Glutathione oxidation increases with age in mitochondria from liver, kidney, and brain of rats. It is striking that this increase was much higher in mitochondria than in whole cells." And mitochondria are at special risk with regard to GSH, because they lack the ability to synthesize GSH or to rid themselves of oxidized glutathione (GSS). Sastre and colleagues found that GSSG levels doubled in old rats compared to young rats, while GSH levels dropped 40% and hydrogen peroxide generation increased 22%." - from The Mitochondrial Theory of Aging (James South). See also Links/Glutathione [Index] and Glutathione edited by Y Sakamoto, Table of Contents. "The role of GSH [Glutathione] as a reductant is extremely important particularly in the highly oxidizing environment of the erythrocyte. The sulfhydryl of GSH can be used to reduce peroxides formed during oxygen transport." - from Tyrosine-derived neurotransmitters.. Examine Glutathione supplements [Images]. Staying Young Forever... Life Extension Foundation, 12/99 - "Lipoic acid is the only antioxidant that can boost the level of intracellular glutathione, a cellular antioxidant of tremendous importance. Otherwise, Vitamin C boosts glutathione levels..." from How to Boost Glutathione Levels. Note that Sulforaphane from broccoli or broccoli sprouts promotes the expression of phase 2 enzymes and glutathione. Note that the manganese-containing mitochondrial form of SOD, MnSOD, is only 8% of the total SOD in rodents, but 50% of the total SOD in man [52]. - pg. 59, Modulations of the Aging Process by Schneider in Handbook of the Biology of Aging, 2nd ed., Finch & Schneider. Advanced Glycation End products (AGEs) and Advanced Lipooxidation End products (ALEs) damage mitochondria through inflammation and elevated ROS levels. Glycation-based damage to mitochondria may be prevented using Carnosine, Luteolin, Benfotiamine, and Pyridoxal-5'-phosphate. (See Julius Goepp MD, Reverse Mitochondrial Damage, Life Extension Magazine, Feb 2010). See Wallace DC (2005), A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine, Annual Review of Genetics 2005 39;359-407 and Muller WE, Eckert A, Kurz C, Eckert GP, Leuner K. (2010), Mitochondrial dysfunction: common final pathway in brain aging and Alzheimer's Disease, Molecular Neurobiology, 2010 June; 41(2-3):159-71. See also Rodriguez MC, MacDonald JR, Mahoney DJ, Parise G, Beal MF, Tarnopolsy MA (2007), Beneficial effects of creatine, CoQ10, and lipoic acid in mitochondrial disorders, Muscle and Nerve (2007) Feb;35(2):235-42 and Ladiges W, Wanagat J, Preston B, Loeb L, Rabinovitch P. (2010), A mitochondrial view of aging, reacive oxygen species and metastatic cancer, Aging Cell 2010 August;9(4):462-5. N-tert-butyl Hydroxylamine [Index, Images, Papers, Patents, Books] is a spin-trap compound sold as a chemical causing a large increase in life span via its hydroxyl radical scavenging capability. See Atamna, et. al, (2000), N-tert-butyl hydroxylamine reverses age-related changes in mitochondria.
Mitochondrially-Targeted Plastoquinone Derivatives [Links, Images, Papers, Patents, Books]. See Antonenko YN, Avetisyan AV, Bakeeva LE, Chernyak BV, Chertkov VA, Domnina LV, Ivanova OY, Izyumov DS, Khailova LS, Klishin SS, Korshunova GA, Lyamzaev KG, Muntyan MS, Nepryakhina OK, Pashkovskaya AA, Pletjushkina OY, Pustovidko AV, Roginsky VA, Rokitskaya TI, Ruuge EK, Saprunova VB, Severina II, Simonyan RA, Skulachev IV, Skulachev MV, Sumbatyan NV, Sviryaeva IV, Tashlitsky VN, Vassiliev JM, Vyssokikh MY, Yaguzhinsky LS, Zamyatnin AA Jr, Skulachev VP (2008), Mitochondria-targeted plastoquinone derivatives as tools to interrupt execution of the aging program. 1. Cationic plastoquinone derivatives: synthesis and in vitro studies, Biochemistry (Moscow), 2008 Dec;73(12):1273-87. See Plastoquinone derivatives [Links, Images, Papers, Patents, Books].
Mitochondrial DNA, or mtDNA [Wikipedia, Links, Images, Video, Papers, Books, LibCong; Links/aging and mitochondria, Images, Video, Papers, Patents, Books; Ben Best/Mitochondria and Aging], defended by MnSOD [Links, Images, Video, Papers, Patents, Books, LifeExtension], glutathione peroxidase, and catalase. See also mitochondrial free radical defense [Links, Images, Video, Papers, Patents, Books, LifeExtension] and lipid peroxidation defense [LifeExtension, Links, Images, Video, Papers, Patents, Books]. The best known treatment to rejuvenate mitochondria is acetyl L-carnitine plus alpha lipoic acid [Links, Images, Papers, Books, LifeExtension; LifeExtension/Alpha Lipoic Acid, Links], to which we might add PQQ. This may be the solution to the mitochondrial theory of aging [Links, Video, Papers, Books, LifeExtension, Amazon]. The human mitochondrial DNA of today is throught to date from Mitochondrial Eve [Links, Papers, Books], who was alive 172,000 to 50,000 years ago. On the other hand, the most recent common ancestor or identical ancestor point is estimated to be at 5,000 to 15,000 years ago. Chimpanzees and man are believed to derive from a common ancestor alive millions of years ago, when the 24-chromosome pair Great Ape gave birth to 23-chromosome pair offspring, two chromosomes fusing to create human chromosome 2 [Wikipedia, Links]. See Human Evolution [Wikipedia, Links, Images, Video, Papers, Books]. Just 600 million years ago, the highest animal on earth was a worm that lived in the sea, a Hydra [Images, Video], in fact. See Evolution [Wikipedia, Links]. Also see Y-chromosomal Adam (Links), the male from whom all living males descended, who is believed to have lived about 60,000 years ago in Africa about the time human migration from Africa took place. See Wallace DC, Shoffner JM, Trounce I, et al. (1995), Mitochondrial DNA mutations in human degenerative diseases and aging, Biochim Biophys Acta 1995 May 24; 1271(1):141-51.
Mitochondrial DNA Repair [Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon]. Acetyl L-Carnitine with alpha lipoic acid [Links] rejuvenates aging mitochondria [Links, Images, Papers, Patents Books; LifeExtension/mitochondrial rejuvenation, Links, Videos], and appears to solve most problems posed by mitochondrial factors in aging [Links, Images, Papers, Patents, Books, Amazon]. (Mitochondrial) Theory of Aging with Dr. Tory Hagan, [50]. From Michael Fossel, Cells, Aging, and Human Disease: Mitochondria turn over every 14 days. (p.68) Defective mitochondria are found mostly in postmitotic cells. Mitochondrial aging may operate independently of senescence. (p.68). "Permissive accumulation of defective mitochondria may be the outcome of cell senescence." (p.69).
Mitofusins [Telomolecular/Mitofusins (including Mitofusin 1 & Mitofusin 2) in Mitochondrial DNA repair; Links/mitofusins, Images, Video, Papers, Patents, Books, LEF]. See
Mitofusin 1 [Links, Images, Papers, Patents, Books, LEF],
Mitofusin 2 [Links, Images, Papers, Patents, Books, LEF],
Mitofusins in mitochondrial DNA repair [Links, Images, Papers, Patents, Books, LEF].
Mitogens [Wikipedia/Mitogen, Links, Images, Video, Papers, Patents, Books]. "A mitogen is a chemical, usually a protein, that stimulates a cell to divide, triggering mitosis. Mitogens trigger signal transduction pathways in which mitogen-activated protein kinase (MAPK) [Links] is involved, leading to mitosis." - Wikipedia/Mitogen. Note that senescence can be modulated by mitogens [Erusalimsky, 2009, Links]. "Excessive mitogenic stimulation caused by forced expression of activated oncogenes is known to induce senescence...(via) a dysregulation of the cellular redox-balance leading to an increase in ROS production which in turn may stimulate p53 activity." - Erusalimsky, 2009. Many telomerase activators [Index], such as the astragalosides, activate hTERT transcription via the MAPK pathway.
Mitotic Chromosomes [Links, Images, Video, Papers, Patents, Books].
Mitotically Competent Cells [Links, Images, Papers, Books, LibCong/Mitosis, Amazon]. Mitotically competent cells are capable of dividing via mitosis. Cancer always arises from mitotically competent cells supporting cellular proliferation, and not from postmitotic cells [Links, Papers, Books, Amazon]. The senescence response is limited to mitotically competent cells. Cellular senescence itself may result from opening of telomere t-loops as telomeres shorten, so that a DNA damage signal is generated in response to an exposed double-strand DNA break leading to cell cycle arrest and cellular senescence. Double-strand DNA breaks originating in free radical or oxidative stress may also trigger cell cycle arrest and cellular senescence as premature stress-induced senescence. Postmitotic cells include mature neurons and differentiated skeletal and heart muscle cells. Quiescent state mitotically competent cells exist in a reversible, growth-arrested state. Liver hepatocytes are usually quiescent, but can be stimulated to proliferate when the liver is damaged.
MnTBAP - mntbap chloride hydrate [Links, Images, Papers, Patents, Books, molecule image]. Mntbap chloride hydrate (MnTBAP) or Manganese (III) Tetrakis (4-Benzoic Acid) Porphyrin chloride (C48H28ClMnN4O8 xH2O), Mol. Weight: 879.15 (anhydrous basis), is a reactive oxygen species (ROS) scavenger, a superoxide dismutase mimetic that is regarded as promising in preventing mitochondrial aging (1). I note that MnTBAP, though effective against mitochondrial aging in many tests, does not pass through the blood-brain barrier, and is usually given by injection. It is not available in pill form as a supplement.
Modified Arabinoxylan Rice Bran (special/Modified Arabinoxylan Rice Bran).
Modified Citrus Pectin and Galectin-3 (Encyclopedia).
Modafinil [Links, Images, Papers, Patents, IAAS, LifeExtension]. Modafinil increases alertness and concentration. See Nootropic drugs and drugs to increase alertness [Papers, Patents, Books, LEF]. Also see drugs to improve concentration [Papers, Patents, Books, LEF].
modRNA Delivery Vehicles (Encyclopedia, Longevity Change Log intro)
Mole Removal [Links, Images, Video, Papers, Patents, Books, Amazon; Links/Facial Mole Removal, Images, Papers, Patents, Books] Moles No More, Moles Treatment.
Molecular Diagnostics [Links, Images, Video, Papers, Patents, Books, Amazon].
Molecular Gerontology [Links, Images, Papers, Patents, Books, LibCong, Amazon, LifeExtension].
Molecular Biology [Wikipedia/Molecular Biology, Wikipedia/Gene_expression, Links/molecular biology, Video, Papers, Books, Amazon/molecular biology, LibCong/molecular biology; Links/the molecular biology of anti-aging medicine, Papers, Books, Amazon]. See Mechanisms of Aging by Ben Best, Aging: The Molecular Concepts from Innovita, Life Extension magazine, International Anti-Aging Systems, the Journal of Longevity and its archives, InfoAging from The American Federation for Aging Research (and its weblinks to other organizations), The American Academy of Anti-Aging Medicine, The Aging Research Center, Quality Counts on anti-aging compounds & anti-aging recommendations with anti-aging & related web sites, The Journal of Experimental Gerontology, Biogerontology, Rejuvenation Research, archived abstracts from the Journals of Gerontology, Series A, SpringerLink's Age, and our Bibliography, [57].
Molecular Biology, Methods of [Index/Protocols, Links, Papers, Books, Amazon/methods of molecular biology; Links/molecular biology protocols, Papers, Books, LibCong/molecular biology protocols; Links/biomolecular protocols, Papers, Books]. See the John M. Walker series from Humana Press and Index/Protocols, below.
Molecular Medicine's Tools & Techniques [MED/unibs/Molecular Medicine's Tools & Techniques, Links/Molecular Medicine, Papers, Books, Amazon; LibCong/Molecular Medicine, The Journal]. See Journals.
Monounsaturated Fats [Links, Images, Papers, Patents, Books, LifeExtension, AnneCollins/Monounsaturated Fats], [55].
Mortality Charts [Longevity/Mortality Charts, Links, Images, Papers, Books, LibCong, LifeExtension].
Mortality Curve [Longevity/Mortality Charts, LifeExtension/mortality curves, Links/mortality curves, Images, Papers, Books; Links/mortality statistics, Images, Papers, Books, Amazon/mortality statistics]. Arxiv/Mortality Curve - the death rate becomes exponential
Aexp[Bt] after 40.
Mortal Somatic Cells [Links, Papers, Patents, Books, Amazon].
MsrA (enzyme peptide methionine sulfoxide reductase) [Links/enzyme peptide methionine sulfoxide reductase, Images, Papers, Patents, Books, LifeExtension], [50s]. MsrA (enzyme peptide methionine sulfoxide reductase) increases Drosophila life span 85%.
mtDNA, mitochondrial DNA [Wikipedia/Mitochondrial DNA, Links, Images, Video, Papers, Patents, Books, LEF, Amazon, LibCong; Links/aging and mitochondria, Papers, Patents, Books, LEF]. Mitochondrial DNA is defended by MnSOD [Index/SOD, Links/MnSOD, Images, Papers, Patents, Books, LifeExtension], gluthione peroxidase [Index], and catalase [Index]. See also mitochondrial free radical defense [Links, Images, Video, Papers, Patents, Books, LifeExtension] and lipid peroxidation defense [LifeExtension, Links, Images, Papers, Patents, Books]. The best known treatment to rejuvenate mitochondria is acetyl L-carnitine plus alpha lipoic acid [Links, Books, LifeExtension; LifeExtension/Alpha Lipoic Acid, Links]. This may be the solution to the mitochondrial theory of aging [Links, Papers, Patents, Books, LifeExtension, Amazon]. Human mitochondrial DNA [Images, Amazon] is throught to date from Mitochondrial Eve [Links, Papers, Books, Amazon], who was alive 172,000 to 50,000 years ago. On the other hand, the most recent common ancestor or identical ancestor point is estimated to be at 5,000 to 15,000 years ago. Chimpanzees and man are believed to derive from a common ancestor alive millions of years ago, when the 24-chromosome pair Great Ape gave birth to 23-chromosome pair offspring, two chromosomes fusing to create human chromosome 2 [Wikipedia, Links]. See Human Evolution [Wikipedia, Links, Images, Video, Papers, Books]. Just 600 million years ago, the highest animal on earth was worm that lived in the sea. See Evolution [Wikipedia/Evolution, Links, Images, Video, Papers, Books].
mTOR (mammalian Target Of Rapamycin) [Index/TOR, Wiki/Mammalian target of rapamycin, Links/Mammalian target of rapamycin, Images, Video, Papers, Patents, Books; Links/mTOR, Images, Video, Papers, Patents, Books; Links/mTOR inhibitors, Images, Video, Papers, patents, Books; Links/mTOR pathway, Images, Video, Papers, Patents, Books]. Caloric restriction and methionine restriction may enhance life span via mTOR pathway inhibition. mTOR inhibitors are useful in dealing with cancer subsequent to operations. See also mTOR pathway. "Encoded by the FRAP1 gene, mTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription.... Decreased TOR activity has been found to slow aging in S. cerevisiae, C. elegans, and D. melanogaster. The mTOR inhibitor rapamycin has been confirmed to increase lifespan in mice by independent groups at the Jackson Laboratory, University of Texas Health Science Center, and the University of Michigan. It's hypothesized that some dietary regimes, like caloric restriction and methionine restriction, cause lifespan extension by decreasing mTOR activity." - Wikipedia. Rapamycin is a caloric restriction mimetic, as is resveratrol. Curcumin, Resveratrol, Caffeine, Quercetin, and irradiated riboflavin are mTOR inhibitors useful in fighting cancer, slowing aging, and extending lifespan.
Mucuna Pruriens [Telomerase Activators/Product B/Velvet Bean Extract (152), Links, Images, Papers, Patents, Books; Index/Dopamine]. Mucuna Pruriens extracted from velvet bean [Images, Papers, Patents, Books] contains typically 15% L-Dopa, so 2000 mg of Mucuna Pruriens yields 300 mg of L-Dopa, a dose typically taken at bedtime to improve dopamine and HGH levels. This happens because dopamine limits hypothalamic somatostatin secretion, resulting in better expression of HGH. Conversely, high glucose depresses neuroprotective HGH levels.
Multicellular organisms [Wikipedia Universe-Review/Multicellular organisms, Links/Multicellular Organisms, Images, Papers, Books, LibCong].
Multiple Sclerosis [Links, Images, Video, Papers, Patents, Books, LifeExtension, LibCong]. "Research conducted at Italy's National Cancer Research Institute indicates that lipoic acid may play a role in preventing or reversing the course of neurological disorders such as multiple sclerosis."
Multivitamin Pills [Links, Links/multiple vitamins and telomere length] were associated with 5.1% longer telomeres in elderly women who took them in a recent study [LifeExtension].
Muscadine Grapes [Wikipedia/Muscadine Grapes, Links, Images, Video, Papers, Patents, Books, LifeExtension], (0), [100]. Muscadine grapes are the grapes highest in resveratrol.
Muscle and Fitness [Muscle and Fitness Magazine, [20]], See also FLEX Magazine, Iron Man Magazine, and Links/Jerry Brainum. See also
Bodybuilding Physiology
____[Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon],
Bodybuilding Supplements
____[Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon],
Exercise Physiology
_____[Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon],
Muscle Physiology
_____[Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon], and
Sports Medicine
_____[Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon].
See Journals.
Myelin Sheath [Links/Anti-Aging for the Myelin Sheath, Images, Papers, Patents, Books, LEF, Amazon; Links/Aging and the Myelin Sheath, Images, Papers, Patents, Books, LEF; Links/Myelin Sheath, Images, Papers, Patents, Books, Amazon/Myelin Sheath, LibCong, LifeExtension; Myelin Sheath Support, Links/Myelin Sheath Support, Images, Papers, Patents, Books, LifeExtension/Myelin Sheath Support].
Myelination [Patents, Books] for the development of the sheath around neurons, continues until age 30 when demyelination [Patents, Books] (deterioration of the sheathing) takes place [1, 2]. Vitamin B12 is quite helpful in myelin sheath support [LifeExtension]. I note that vitamin B12 is also available in typical homocysteine shields, and that homocysteine inhibitors [typical, Links] including vitamin B12 should also be useful for myelin sheath support. Between 21 and 77, nerve impulse velocity declines from 57 m/sec to 48 m/sec, and the amplitude of sensory potentials drops from 43 to 21 microvolts, 51%. A decline of 1 m/sec per decade is seen between 20 and 55 years of age, and 3 m/sec per decade after 55. Propagation velocity degradation is due to changes in the myelin sheath, and unmyelinated nerves are spared. From Chapter 23, "Changes in the Peripheral Nervous System" by Thierry Maisonobe and Jean-Jacques Hauw, in Principles of Neural Aging by Dani, Hori, and Walter. See also Google links on Myelin sheath support. Typical ingredients in Myelin sheath support supplements include:
Amla Fruit Extract [Images, LifeExtension; Links/Application, Papers, Patents, Books],
Ashwagandha [63s] [Images, LifeExtension; Links/Application, Papers, Patents, Books],
Asian Ginseng Root [Images, LifeExtension; Links/Apps, Papers, Patents].
Astragalus Root Extract [Images, LifeExtension; Links/Apps, Papers, Patents, Books],
Bacopa Plant Extract [Images, LifeExtension; Links/Application, Papers, Patents, Books],
Black Pepper Fruit Extract [Images, LifeExtension; Links/Apps, Papers, Patents, Books],
Boron Chelate [Images, LifeExtension; Links/Apps, Papers, Patents, Books],
Bromelain [Images, LifeExtension; Links/Apps, Papers, Patents, Books] [36s]p,
Chinese Salvia Root [Images, LifeExtension; Links/Apps, Papers, Patents, Books],
European Elderberry [Images, LEF; Links/Apps, Papers, Patents, Books],
Ginger Root [Images, LEF; Links/Apps, Papers, Patents, Books],
Hawthorn Berry Extract [Images, LEF; Links/Apps, Papers, Patents, Books],
Hericium Erinaceus Mycelium [Images, LEF; Links/Apps, Patents, Papers],
Indian Olibanum Gum Resin [Images, LEF; Links/Apps, Patents, Papers],
Licorice Root Extract [Images, LEF; Links/Apps, Papers, Patents, Books],
Long Pepper Fruit [Images, LEF; Links/Apps, Papers, Patents, Books],
Saffron [Index, Images, LEF; Links/Apps, Papers, Patents, Books],
Shilajit Mineral Resin [Images, LEF; Links/Apps, Papers, Patents, Books],
Tienchi Ginseng Root [Images, LEF; Links/Apps, Papers, Patents, Books],
Turmeric Root Extract [Images, LEF; Links/App, Papers, Patents, Books] (curcumin) [40s],
Yogaraj Guggul Gum Resin [Images, LEF; Links/Apps, Patents, Papers].
Note that benfotiamine [Links, Images], a lipid-soluble form of vitamin B1 found in onions, can restore nerve conduction velocity [Links] in aging specimens. Ordinary vitamin B1 helps, but benfotiamine is more effective. Nerve conduction velocity is related to the diameter of the nerve and the degree of myelination of the axon of the nerve. Recent research (2008-2010, BBC News) in myelin sheath repair [Papers, Patents, Books] has focused on using neural stem cells to repair myelin sheath damage due to multiple sclerosis (MS). See The Centre for Myelin Repair [Video] at Cambridge University and neural stem cells for brain repair [Video, Papers, Patents, Books].
Both resveratrol and NAD+ (NADH) reduce neural degeneration and extend neural cell lifespan. Increased nuclear NAD+ biosynthesis and SIRT1 activation prevent axonal degeneration in nerve cells [Images]. It is suspected that adequate intracellular NAD+ levels are essential for neuronal survival. There is a 1:1 stoichiometry between intracellular NAD+ content and sirtuin-mediated deacetylation. This fact should be directly related to optimal dosages of NAD+. Ray Sahelian promotes 2.5 mg of NADH [Images] every other day, or perhaps as much as 5 mg every other day. At higher levels, stomach upset is sometimes observed. Nicotinamide (vitamin B3, or niacin) is converted to NAD+. Saffron [Images] contains crocin [Images], which prevents damage to cells that make myelin in the brain, and decreases neuroinflammation and decreases neurological impairment. (In the News, Life Extension Magazine, Nov 2012).
References
[1] Eric Braverman, MD, and Bruce Scali (2015),
Reverse Mild Cognitive Impairment, Life Extension Magazine March 2015.
[2] Van Dinteren R, Arns M, Jongsma M. et al. (2014),
P300 development across the lifespan: a systematic review and meta-analysis,
PLoS One 2014 Feb. 9(2):e87347.
Myostatin Inhibitors [Links, Images, Video, Papers, Patents, Books, LifeExtension, Amazon; Wikipedia/Myostatin; Creatine supplements, Follistatin supplements, Whey Protein supplements; Sarcopenia; Anti-Aging_Firewalls/Sarcopenia: Myostatin Section]. Myostatin produced by the myostatin gene (a member of the TGF-beta family of genes) inhibits muscle growth. Eliminating the gene produces a muscle-doubling effect [Images]. Myostatin inhibits the differentiation of myoblasts into mature muscle fibers. Mystatin acts on muscle tissue by binding the cell-bound activin type II receptor, and by inhibiting AKT, which is sufficient to induce muscular hypertrophy. Myostatin inhibitors such as follistatin allow more muscle growth and are found in fertilized hens eggs, for instance. Testosterone is also a myostatin inhibitor (Kovacheva, Hikim, Shen, Sinha and Sinha-Hikim, 2010). Creatine is a myostatin inhibitor that decreases myostatin levels. Whey protein decreases myostatin levels most effectively when taken prior to a workout, rather than after. Cortisol inhibits myogenin, which promotes muscle repair and growth, and enhances myostatin expression, which inhibits muscle growth, and inhibits other factors promoting muscle growth, including the mTOR muscle synthesis pathway. Therefore cortisol inhibitors can act like myostatin inhibitors [Images] when cortisol is elevated.
Myostatin Inhibitors
Bodybuilding exercise itself. (Progessive resistance exercise).
Cortisol inhibitors (when cortisol is high).
Creatine monohydrate.
Follistatin (from fertilized hen's eggs).
Testosterone.
Whey protein.
Perhaps spinach, which causes more muscle synthesis after exercise via beta-ecdysterone (20-hydroxyecdysone), is also a myostatin inhibitor (check). Perhaps HGH and IGF-1, both of which promote tissue growth, are myostatin inhibitors (check). Myostatin inhibitors may be useful in treating sarcopenia. "A University of Pittsburgh study found that participants who performed nine weeks of heavy resistance training decreased myostatin expression by 37 percent." - eHow:Reduce Myostatin. "Here, we show that myostatin is a pro-oxidant and signals the generation of ROS in muscle cells. Myostatin, a transforming growth factor-beta (TGF-beta) family member, has been shown to play an important role in skeletal muscle wasting by increasing protein degradation. Our results here show that myostatin induces oxidative stress by producing ROS in skeletal muscle cells through tumor necrosis factor- (TNF-) signaling via NF-kB and NADPH oxidase. " - Sandhya Sriram, Subha Subramanian, Durga Sathiakumar, Rithika Venkatesh, Monica S. Salerno, Craig D. McFarlane, Ravi Kambadur, Mridula Sharma (2011), Modulation of reactive oxygen species in skeletal muscle by myostatin is mediated through NF-kB, (PubMed Abstract), Aging Cell, December 2011, 10(6):931-948. See also Morissette MR, Cook SA, Buranasombati C, Rosenberg MA, Rosenzweig A. (2009), Myostatin inhibits IGF-I-induced myotube hypertrophy through Akt, American Journal of Cell Physiology, November 2009, 297(5):1124-32. Also see Craig McFarlane, Gu Zi Hui, Wong Zhi Wei Amanda, Hiu Yeung Lau, Sudarsanareddy Lokireddy, Ge XiaoJia, Vincent Mouly, Gillian Butler-Browne, Peter D. Gluckman, Mridula Sharma, and Ravi Kambadur (2011), Human myostatin negatively regulates human myoblast growth and differentiation, American Journal of Physiology - Cell Physiology, November 2011; 301(5):195-203. Jacquemin V, Furling D, Bigot A, Butler-Browne GS, Mouly V (2004), IGF-1 induces human mytotube hypertrophy by increasing cell recruitment, Exp Cell Res 299: 148-158, 2004. Langley B, Thomas M, Bishop A, Sharma M, Gilmour S, Kambadur R (2002), Myostatin inhibits myoblast differentiation by down-regulating MyoD expression, J. Biol Chem 277: 49831-49840, 2002. McCroskery S, Thomas M, Maxwell L, Sharma M, Kambadur R (2003), Myostatin negatively regulates satellite cell activation and self-renewal, J Cell Biol 162: 1135-1147, 2003. Thomas M, Langley B, Berry C, Sharma M, Kirk S, Bass J, Kambadur R (2000), Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation, J Biol Chem 275: 40235-40243, 2000. Yarasheski KE, Bhasin S, Sinha-Hikim I, Pak-Loduca J, Gonzalez-Cadavid NF (2002), Serum myostatin-immunoreactive protein is increased in 60-92 year old woman and men with muscle wasting, J Nutr Health Aging 6: 343-348, 2002.

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