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Damiana [Links/Damiana, Images, Video, Papers, Patents, Books, LifeExtension]. Damiana is a ligand of the progesterone receptor that is used as an aphrodisiac. It is conjectured to function as a telomerase activator like progesterone.
Dangerous Drug Interactions [Links, Images, Video, Papers, Books, LibCong, Amazon, LifeExtension].
Dark Chocolate [Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Cocoa contains PQQ [Index/PQQ, Links/Pyrroloquinoline Quinone, Images, Papers, Patents, Books; Links/Chocolate polyphenols, Images, Papers, Patents, Books, LifeExtension/chocolate polyphenols, Amazon/chocolate polyphenols], [25k]. See the index entries for Chocolate, Cocoa, and PQQ, which supports mitochondrial biogenesis.
Dark circles under the eyes [Links, Images, Papers, Patents, Books, LifeExtension; Images/Supplements to treat dark circles under the eyes] . Dark circles under the eyes are sometimes seen in old people, including Pope Benedict XVI. Medicines: Hylexin. According to the Hylexin team, dark circles are caused by oxidation of hemoglobin in the capillary matrix of the peri-orbital eye area, where the capillaries leak blood that begins to oxidize through hemoglobin degradation. Perhaps more vitamin C or bilberry extract (or gotu kola or escin or astragalosides useful in wound healing) would help strengthen the dark circle capillaries, since tissue-strengthening collagen is typically obtained from a process requiring vitamin C. I note that some folk remedies involve treating the afflicted area with vitamin C-rich lemon juice. VitalEyes by Rejuvenex, formulated to combat dark circles, contains other compounds to increase collagen synthesis. Vitamin C plus Bilberry extract, a vessel strengthener, might be indicated. For an effective approach emphasizing the blood-clotting control factor vitamin K1 and the anti-coagulant yarrow root, see Dark Circles Eye Cream from Skin Energizer.. There are alternate theoretical models of what is behind dark circles. I note that the OhioHealth/MayoClinic recommends skin creams containing Vitamin C or Vitamin K1 [Index], alpha hydroxy acid, and kinetin. See also  on anti-aging skin creams and aging skin, and the index entry Index/Skin. Vitamin K1 skin cream is used on bruises and dark circles to stop subcutaneous bleeding, since it promotes clotting, allowing microstructure associated with veil cells to heal. The fibroblast-like veil cells surround microscopic vessels in the skin's dermis, but become less numerous with age. They secrete factors which maintain the basement membranes surrounding tiny vessels in the skin. Other promising treatments now include skin creams with epidermal growth factor (EGF) and acidic Fibroblast Growth Factor (FGF1), which lengthen telomeres in epidermal keratinocytes and restore dermal fibroblasts responsible for maintaining the extracellular matrix. The growth factor approach should be capable of restoring the youthful number density of veil cells. Colostrum [List] in colostrum skin creams contains many useful telomerase-activating growth factors including TGF-alpha, EGF, IGF-1, IGF-2, VEGF, FGF, and PDGF for restoring dermal fibroblast telomere length to obtain more youthful patterns of gene expression and TGF-beta for reconstructing collagen and elastin in the extracellular matrix. I think it may be also be useful to apply Astragaloside IV skin cream (Terraternal) [or GAIA Herbs Astragalus Root Extract in glycerin at 1 mg astragalosides per 30 drops] over a period of several years to regrow dermal fibroblast telomeres in order to rejuvenate dermal fibroblasts [Images]. Endothelial cells lining veinous structures may be restored with orally bioavailable telomerase activators including nitric oxide promoters (arginine, citrulline, pomegranate, resveratrol, cocoa powder), cycloastragenol (TAT2, TA-65, TAT0002), Product B, astragalus root, and astragalus root extract. These also tend to restore dermal fibroblasts over an extended period to patterns of youthful gene expression in which they better maintain the extracellular matrix with collagen and elastin, escaping from their old-age phenotype in which they secrete matrix metalloproteinases such as collagenase and stromelysin that attack the extracellular matrix, and in which they suspend the activity of matrix metalloproteinase inhibitors such as TIMP1 and TIMP3.
Death Clock [Death Clock.com, Mortality Charts], , [22s].
Death, Leading Causes of (Encyclopedia).
Death Hormone theory [Links, Images, Papers, Patents, Books, Amazon, LifeExtension], W. Donner Denkla DECO theory [Links, Images, Papers, Books, Amazon], [22s].
de Grey, Aubrey [Index/Aubrey de Grey, SENS, Wikipedia, Links, Images, Videos, Papers, Patents, Books, Wikipedia, LifeExtension]. Video: Aging of the Other Genome (Aubrey D.N.J. de Grey on Aging of the Mitochondiral Genome, 62 minutes.) See The Mitochondrial Free Radial Theory of Aging by Aubrey D.N.J. de Grey and Ending Aging by Aubrey de Grey and Michael Rae.
Titia de Lange [Rockefeller University Laboratory Head, Links, Images, Videos, Papers, Patents, Books, LifeExtension].
Titia de Lange is a bioscientist and head of the Laboratory of Cell Biology and Genetics at Rockefeller University who has produced many important papers and patents (based on sophisticated experimental technique) on telomeric proteins managing telomere loop control. She worked extensively on telomere control proteins including tankyrase 1 and TRF1, and wrote a classic paper on shelterin and many other impacting bioscience papers. Titia de Lange is one of the world's most prolific telomere biologists. See Titia de Lange (2005), Shelterin: the protein complex that shapes and safeguards human telomeres, Genes and Development, 2005, 19:2100-2110. Titia de Lange received the 2011 Vilcek Prize in Biomedical Science. "Leon Hess Professor and head of the Laboratory of Cell Biology and Genetics at Rockefeller University, has received the 2011 Vilcek Prize in Biomedical Science for her body of research on mechanisms that help maintain genome stability. The prize includes a $100,000 cash award and a trophy created by noted designer Stefan Sagmeister." According to Rockefeller University, "Dr. de Lange earned her Ph.D. in biochemistry from the University of Amsterdam and the Netherlands Cancer Institute in 1985. From 1985 to 1990 she was a postdoctoral fellow in the laboratory of Nobel laureate Harold Varmus at the University of California, San Francisco, where she was one of the first to isolate the telomeres of human chromosomes."
Dementias [Wikipedia/Dementia, Links, Images, Papers, Patents, Books, Amazon, LibCong, LifeExtension, Images/Alzheimer's Disease Brain, Images/Vascular Dementia Brain; Index/Brain Deterioration, Index/Cognitive Decline; Hypoperfusion, Leukoaraiosis, Neurobiology of Aging, Neurodegenerative Disorders, Neurological Aging, Neuronal Regeneration; Alcoholism].
See the Graphic/Causes of Dementia. Dementias affect 20% of people over 80 and may be classified into 3 main types and the less common dementias:
__(1)Alzheimer dementias (Index, Images, Papers, Patents, Books),
__(2) Vascular dementias (Images, Papers, Patents, Books), including
_____Strokes (Index, Images, Papers, Patents, Books) and
_____Microinfarct dementias (Images, Papers, Patents, Books)
______due to the loss of vascular supply,
__(3) Parkinson's (Index, Images, Papers, Patents, Books),
__(4) Other less common dementias:
_____Hypothyroidism (Images, Papers, Patents, Books),
_____Myxedematous dementia (Images, Papers, Patents, Books),
_____Lewy body disease (Index, Images, Papers, Patents, Books),
_____Pick disease (Images, Papers, Patents, Books), and
_____Wernicke-Korsakoff syndrome (Images, Papers, Patents, Books).
The most common cause of dementia is Alzheimer's Disease [Images], which involves apoptotic cascades that irreversibly destroy neural tissue triggered by Amyloid Beta and presenilins; caused by diet, diabetes, tobacco use, genetics, vascular disease, and toxin exposure, exhibiting neuronal loss of cholinergic and other neurons, necrotic areas, neurofibrillary tangles composed of tau proteins, and frontal and limbic amyloid plaques. (Fossel, p.230). Note that microglia are a growing source of inflammatory mediators in older brains after exposure to amyloid-beta peptide. Microglia [Images] are monocytes, which also play an inflammatory role as foam cells in atherogenesis and as osteoblasts in osteoarthritis. It may be that endothelial and microglial senescence are key factors in central nervous system aging [Books, Images, LifeExtension]. (Fossel, pp.233-237). It is noteworthy that dementias do not show up in Werner's Syndrome patients, prematurely old children with short telomeres who exhibit atherosclerosis, wrinkled skin, and many other old age symptoms, except dementia. The role of iron and copper poisoning from beef in old people may be important here, as fish-eating Japanese have a relatively low level of dementia in their old people who do without high levels of iron and copper from beef in their diet. Mice and rats fed high-iron diets develop dementia as elderly mice. There is also the insight that Alzheimer's Disease is due to sustained hyperglycemic and diabetes-like effects in old people, generating advanced glycation end products (AGEs) and follow-on inflammation leading to the disease. "Beer belly" has been linked to Alzheimer's disease, dementias and smaller brain volume. High levels of the appetite-suppressing hormone leptin have been linked to reduced likelihood of Alzheimer's disease. Also, a blow on the head can result in inflammation making the victim more likely to eventually exhibit Alzheimer's Disease, and inflammation of the gums is sometimes blamed for Alzheimer's Disease. Perhaps microglial senescence in Werner's Syndrome does not precipitate Alzheimer's Disease in the absence of amyloid-beta stimulation originating in inflammation of hyperglycemic, diabetic, traumatic, or dental origin. TNF-alpha inhibitors [Papers] like Enbrel have been very useful in treating Alzheimer's Disease. Also consider the TNF-alpha inhibitor Luteolin (found in celery, green pepper, perilla , parsley, sage, peppermint, and camomile tea) and Parsely, Sage, Rosemary, and Thyme. See also Molovsky AV et al. (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during aging. Nature 443 : 448-52. (Index/p16). Note that p16INK4a may be kept down with Nerve Growth Factor, which can be boosted with acetyl L-carnitine plus alpha lipoic acid, PQQ (Pyrroloquinoline Quinone), rosemary extracts, or huperzine A. Other factors lowering P16INK4A include retinol or retinoic acid from carrots, resveratrol, and exercise. High P16INK4A levels follow from aging, smoking, and lack of exercise. See also Mark P. Mattson (2007), Calcium and neurodegeneration, Aging Cell, Volume 6, Issue 3, pages 337–350, June 2007.
Demethylation of Senescent Cells & DNA Demethylation [Links/DNA methylation, Images, Papers, Patents, Books; Links/DNA Demethylation, Images, Papers, Patents, Books, LifeExtension; Links/demethylation in senescent cells, Images, Papers, Patents, Books; Books/epigenetic regulation in senescent cells, Links/causes of DNA demethylation; Index/Methylation]. Methylation of genes is used in the development of placental mammals including humans to silence gene promoters after their developmental role is over, or to switch on genes controlled by an insulator in charge of an enhancer. Life Extension Magazine promotes SAMe [Links] as a cure for undesirable DNA demethylation, noting that "Cellular aging is partially caused by de-methylation". Folic acid is also useful in maintaining methylation.
Dental Work [Dental, with Wichita Dentists & Supplies, Links/Dental Fillings, Books, Links/Dental Cavities & Repair, Books/Dentistry, LibCong, Links/Dentistry, Links/Tooth Sealants, Books/tooth sealants].
Deprenyl [IAAS/Deprenyl, (selegiline) QC, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon, Ben Best, LifeExtension; Books/in_aging]. Deprenyl has extended the maximum life span of a number of mammals, doubling remaining life spans, , [11s].
Deprenyl IAAS/Deprenyl article 2 - the liquid deprenyl citrate is considered to be superior. (testimony). Deprenyl elevates SOD and catalase levels, and improves longevity, antibody response, and cognitive function in geriatric dogs. It is a Mao-B inhibitor, inhibiting re-uptake of dopamine, and is used in the treatment of Parkinson's disease and for life extension. Higher dopamine expression is associated with improved mobility and higher activity levels in aging specimens.
Depression [James South/Depression, Links/depression, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon] in anti-aging medicine. See Antidepressants [Index, Links, Images, Video, Papers, Patents, Books, LifeExtension].
Dermatology [Index/Geriatric Dermatology, Wikipedia/Dermatology, Links, Images, Video, Papers, Patents, Books, Amazon, Books/Aging Skin, Books/Skin Blemish Removal, Books/skin lesions, Links/skin lesions, LibCong/dermatology] See Index/Skin, Index/Lesions, Index/Purpura, Index/Senile Purpura, Index/Veil Cells, and Index/Wrinkles and Wrinkle Treatments.
Desmopressin [IAAS/Desmopressin, Links, Images, Video, Papers, Patents, Books, Amazon], (5). Desmopressin is a memory improver. Sounds like "Death's mo' pressin'."
Deuterium Theory of Aging [article, Links/Deuterium and DNA damage, Images, Video, Papers, Patents, Books; Links/Deuterium-depleted water, Images, Video, Papers, Patents, Books]. Deuterium in water is thought to contribute to DNA damage, and deuterium-depleted water, or Dd-water, may be taken to reduce damage to DNA from deuterium [Wikipedia]. Deuterium water is toxic, and the associated problems seem to stem from the effect of deuterium on the hydrogen bond. Deuterium bonds are stronger and shorter than normal hydrogen bonds, sometimes modifying the shape of an enzyme. Deuterium-depleted water has contributed to the survival time of breast cancer patients after metastases have been observed. Dd-water may be obtained from glaciers at high altitude, as for instance Hunza water [Links, Images, Papers]. Natives from this region report living extended lifespans on the order of 120-140 years. Plants can be constructed to produce deuterium-depleted water on a large scale [article], and it is available in liter bottles like a soda beverage. I note that life at high altitude produces hypoxia and higher levels of the transcription factor HIF-1, which directly promotes hTERT transcription to improve longevity.
Detoxification [Links, Images, Papers, Patents, Books, LibCong, Amazon, LifeExtension, Ben Best; Index/Purge the Poisons Theory of Rejuvenation]. Detoxification fails in aging due to defective methylation, [69s], (12). Chelation of metal ions is also an issue in detoxification. Iron deposits in the brain from beef can accelerate lipid peroxidation via Fenton reactions to produce inflammation leading to Alzheimer's Disease or dementia, for instance. The acceleration of lipod peroxidation via an iron-catalyzed Fenton reaction "chain reaction" process is well described in The Mitochondrial Free Radical Theory of Aging by Aubrey de Grey. Unchelated aluminum leads to neurofibrullary tangles. Copper helps cancer spread. Mercury poisoning from fish and sea food is possible. Drugs and nutraceuticals supporting metal ion chelation applications include:
___Carnosine (iron, copper, and heavy metal ions),
___Cranberry Extracts (iron),
___Curcumin (iron, copper, and aluminum),
___EDTA (iron, copper and heavy metal ions),
___EGCG found in Green Tea crosses blood-brain barrier (iron),
___Lipoic Acid (iron),
___N-Acetyl Cysteine (NAC) (iron, copper, mercury, arsenic, cadmium, and lead),
___Pomegranate extracts (iron),
___Quercetin (iron and copper), and
___Resveratrol (copper only).
Dextrose [Links, Images, Video, Papers, Patents, Books]. Dextrose is the D-form of glucose [Images]. Glucose is the most primitive sugar found in cells, and is polymerized to form starch and cellulose. It is taken with whey protein or whey hydrolysates at 25-50 grams of dextrose after workouts to spike insulin in bodybuilding in a post-workout shake.
DHA [Telomerase Inhibitors/DHA, Ben Best/DHA, Wikipedia, Links/DHA and aging, Images, Video, Papers, Patents, Books, LifeExtension, Ben Best; Links/Separation of DHA from fish oil, Images, Papers, Patents, Books, Index/Brain Growth and Development, Index/Brain Cancer; Heart Attack (Optimal Cardiac Defense)]. DHA (docosahexaenoic acid) is a brain food fish oil component, important for the developing human, [30s]. Salmon has the highest content of DHA of any fish, ranging from 2000 to 3000 milligrams per 6 ounce serving. Swordfish contains 1390 mg per 6 ounce serving. DHA is also "critial for optimal brain health and function at all ages of life". DHA is associated with dendrite formation and complexity, brain synaptogenesis, and corneal nerve regeneration in experimental animals. The other component of fish oil is EPA (eico-sapenaenoic acid). DHA may not be produced in the body from ALA in flax seed oil, as is sometimes claimed [Links, Images]. DHA induces apoptosis in neuroblastoma cells and protects normal neural cells from apoptosis. (LEF, June 2010; The FASEB Journal, 2010, Mar;24(3):906-15.) DHA is a telomerase inhibitor for cancer cells (REF). See also Links/DHA in Brain Growth and Development. See Russell L. Blaylock, MD (2008), DHA Supports Brain Development and Protects Neurological Function, Life Extension Magazine, Jan 2008. DHA reduces inflammation and improves the fluidity of cell membranes, improving their ability to release neurotransmitters. DHA improves the levels of neurotransmitters such as dopamine. Dopamine improves the expression of HGH, so that DHA improves HGH expression, explaining why fish fat improves man's height in St. Petersburg, Russia. HGH is a telomerase activator [List], so DHA should be a telomerase activator for normal, healthy cells by improving dopamine expression to boost HGH. DHA measurably reduces depression and levels of hostility. See Lukiw WJ, Bazan NG (2008), Docosahexanoic acid and the aging brain, Journal of Nutrition 2008 Dec; 138(12):2510-14. Note that DHA makes up 30% of the brain, and 50% of the retina (Russell L. Blaylock, 2008). DHA deficiency has been linked to Alzheimer's Disease, and is associated with macular degeneration [Index]. See
DHA and Macular Degeneration [Links, Images, Video, Papers, Patents, Books; Index/Macular Degeneration]. The telomerase inhibitor DHA is anticancer, effective in preventing and treating colorectal adenocarcinoma [REF, Images, Papers, Patents, Books]. Only about 20 mg/day of DHA is available from a vegan diet, which may be DHA-supplemented to 2 grams/day DHA to avoid old age dementia. Up to 9 grams/day of fish oil is progressively beneficial. At this time, DHA can be extracted from algae (algal) and is often taken from fish oil or krill oil, which also contains phospholipids for the cell membrane. See Kirk Stokel (2012), DHA an Essential Brain Food, Life Extension Magazine, November 2012. "Blood flow to memory-critical parts of the brain increases after DHA supplementation, and new brain cells form in older animals." See also Dyall SC, Michail GJ, Michael-Titus AT (2010), Omega-3 fatty acids reverse age-related decreases in nuclear receptors and increase neurogenesis in old rats, Journal of Neurological Research, 2010 Aug1;88(10):2091-102.
DHA and Ceramides
DHA improves ceramide expression [Links, Images, Video, Papers, Patents, Books]. This is useful to restore skin elasticity, skin color, and skin barrier protection [Micheal Downey, Life Extension Magazine, 2014]. This may be achieved directly using oral phytoceramides. DHA activates sphingomyelinase to generate ceramide by the hydrolysis of sphingomyelin: [Links, Papers, Patents, Books].
DHA and Phosphatidylserine [Index/Phosphatidylserine]
DHA regulates the brain’s concentration of phosphatidylserine, and diets low in DHA decrease phosphatidylserine levels in the hippocampal region of the brain associated with memory consolidation , .
 Russell L. Blaylock, MD (2008),
DHA Supports Brain Development and Protects Neurological Function,
Life Extension Magazine January 2008.
 Salem N, Jr., Litman B, Kim HY, Gawrisch K. (2001),
Mechanisms of action of docosahexaenoic acid in the nervous system, Lipids 2001 Sep;36(9):945-59.
DHEA (Dihydroepiandrosterone) [Telomerase Activators/DHEA, Smart Drugs/DHEA, QC, Wikipedia/DHEA, Links/DHEA, Images, Video, Papers, Patents, Books, LifeExtension, Ben Best; Links/DHEA and Aging, Images, Papers, Patents, Books; Chart/Decline in DHEA levels with advancing age]. , [18s], [28s]. DHEA (Dihydroepiandrosterone) is anticancer and may inhibit the greying of hair [74s] [Books, LifeExtension/article]. DHEA opposes high cortisol levels, lowering blood sugar to prevent the production of Advanced Glycation End products (AGEs) leading to inflammation supporting the evolution of diabetes and Alzheimer's Disease. Old age cognitive decline is partly prevented by DHEA, because DHEA increases the levels of neurotransmitters important for short- and long-term memory and learning. As Dr. Jerry Brainum recently pointed out in Iron Man, DHEA boosts IGF-1 levels [Links, Papers]. IGF-1 activates telomerase with anti-aging effect, so DHEA is an indirect telomerase activator (TA/DHEA) via the IGF-1 pathway DHEA -> IGF-1. . Furthermore, DHEA is a testosterone precursor, and androgens such as testosterone have telomerase-activating effect in heart cells, muscle tissue and hair follicles. DHEA improves testosterone expression without impacting the gland of Leydig in the testicles, so that it perks up castrated specimens. DHEA (IAS Bulletin) is another bone-mass improver opposing osteoporosis and sarcopenia (age-related decrease in skeletal muscle mass). "A group of researchers found that DHEA increased the growth of human brain cells in an in-vitro study. DHEA treatment caused as much as a 29% increase in the number of neurons produced by stem cells. Low endogenous levels of DHEA are found in a number of different dementias and Alzheimer's Disease."
Jack LaLanne Mortality Factors
Low DHEA is also associated with impaired immune system performance, and is believed to be a factor in the death Jack LaLanne at 96 due to pneumonia. At age 95, Jack Lalanne underwent surgery to replace the aortic valve after suffering from aortic stenosis, possibly for using green leafy vegetables as a vitamin K2 source, when Swiss cheese or MK-7 supplements would have worked fine to prevent calcification. See William Falloon (2011), Avoiding the Catastrophic Event, Life Extension Magazine, November 2011. Note that telomere shortening weakens the immune system, which may then be improved by taking telomerase activators such as astragalus root extract to restore telomere length in immune system cells.
7-Keto DHEA (3-Acetyl-7-oxo DHEA) [Links/7-Keto DHEA, Images, Video, Papers, Patents, Books, LifeExtension; Links/3-Acetyl-7-oxo DHEA, Images, Video, Papers, Patents, Books, LifeExtension; Memory Enhancing Nutraceuticals]. 7-Keto DHEA (3-Acetyl-7-oxo DHEA) is a metabolite of DHEA. DHEA is produced by the adrenal glands to form testosterone. 7-Keto DHEA increases metabolic rate without producing testosterone or estrogens by increasing the expression of T3 thyroid hormone. Thyroid hormone T3 rapidly induces activation of AMPK to supply ATP via catabolic reactions for metabolic processes, including autophagy of cellular junk in senescent cells and apoptosis of senescent cells. In addition, 7-Keto DHEA is believed to promote metabolism at the mitochondrial level. 100-200 mg/day may be taken in divided doses. - (dosage after Muscle and Fitness Magazine, 2010). Note that thryroid hormone T3 from 7-Keto DHEA improves the expression of UCP3, which protects mitochondria from lipid-induced oxidative stress. According to LEF, 7-Keto DHEA also boosts the levels of 3 thermogenic enzymes to increase resting metabolic rate:
 Michael Downey (2012),
Age-Related Metabolic Decline and Weight Gain,
Life Extension Magazine, December 2012.
 Perrini S, Laviola L, Natalicchio A, Giorgino F (2005),
Associated hormonal declines in aging: DHEAS,
J Endocrinol Invest 2005;28 (3 Suppl):85-93.
 Johnson MD, Bebb RA, Sirrs SM (2002),
Uses of DHEA in aging and other disease states,
Ageing Res Rev 2002 Feb;1(1):29-41.
 Enomoto M, Adachi H, Fukami A, et al. (2008),
Serum dehydroepiandrosterone sulfate levels predict longevity in men: 27-year followup study in a community-based cohort (Tanushimaru study),
J Am Geriatr Soc 2008 Jun;56(6):994-8.
 Sanchez J, Perez-Heredia F, Priego T, et al. (2008),
Dehydroepiandrosterone prevents age-associated alterations, increasing insulin sensitivity,
J Nutr Biochem 2008 Dec;19(12):809-18.
 Ravaglia G, Forti P, Maioli F, et al. (2002),
Dehydroepiandrosterone-sulfate serum levels and common age-related diseases: results from a cross-sectional Italian study of a general elderly population,
Exp Gerontol 2002 May;37(5):701-12.
DHT (dihydrotestosterone) [Links/Dihydrotestosterone, Images, Papers, Patents, Books, LifeExtension; Links/Dihydrotestosterone and hair loss, Papers, Patents, Books, LifeExtension]. [74s]. Baldness often comes from dihydrotestosterone (DHT) created from testosterone by the enzyme 5-alpha-reductase, which impacts the hair follicle. It was noticed early on that testosterone could be blocked by testicle removal, in which case the hair did not fall out. A more popular approach is to topically apply saw palmetto with beta sitosterol, or finasteride or dustasteride to block 5-alpha-reductase. L-lysine [Images, Patents] also blocks 5-alpha-reductase, an approach described in the patent literature. Recently, we have read that green tea blocks DHT formation and stops baldness. I gather one may stop baldness by rubbing green tea or green tea extract into the scalp, or by applying a skin cream containing green tea, as many sunburn creams do. Another approach is to use Rogaine, which is based on minoxidil, although the mechanism is not clear for this approach to treatment. Also, lost hair may be restored with astragalosides such as astragaloside IV, because the process depends on changes in gene expression that follow cellular senescence. Experiments at Artandi Labs indicate that products like Terraternal Astragaloside IV skin cream, which counteract cellular senescence in the scalp, work to restore hair, as does astragalus extract. Experimenters like Vince Giuliano also report hair growth returning subsequent to application of astragaloside IV.
Diabetes, type 1 & type 2 (adult onset diabetes) [Wikipedia/Diabetes, Links/Diabetes, Images, Video, Papers, Patents, Books, Amazon, LifeExtension, LibCong; Links/Diabetes and Aging, Images, Video, Papers, Patents, Books, LifeExtension; Links/Type 1 Diabetes, Images, Video, Papers, Patents, Books, LifeExtension; Type II Diabetes; Links/Type 2 Diabetes, Images, Video, Papers, Patents, Books, LifeExtension, Encyclopedia].
"Diabetes mellitus can be defined as a group of syndromes characterized by polydipsia (chronic excessive thirst and fluid intake), polyphagia (excessive eating), glycosuria (excessive glucose in the blood) and acetone breath i.e. the breath of the patient smell of acetone due to an abnormal increase of ketone bodies in the blood." (P.Kanetkar, R. Singhal, and M. Kamat (2007), Gymnema Sylvestre: A Memoir, Journal of Clinical Biochemistry and Nutrition, 41, 77-81, September 2007). There are two types of diabetes: Type 1 (insulin-dependent diabetes) and Type 2 (non-insulin dependent diabetes or adult-onset diabetes). Diabetes produces hyperglycemia with consequent glycation eventually mimicking many symptoms of old age. Diabetes can begin with high cortisol levels due to stress that drive blood sugar up, especially in combination with a high-sugar diet, to help the system in response to emergencies, resulting in high insulin levels finally leading to loss of sensitivity to insulin, causing the pancreas to secrete still more insulin until hyperinsulinemia is produced, increasing fat storage. This hyperinsulinemia is a precursor to type 2 (adult-onset) diabetes in which the pancreas cannot sustain insulin production. Prevent diabetes by eating a low-sugar diet, exercising (9) to elevate DHEA naturally, by keeping stress low, and by perhaps by including supplemental DHEA to balance out high cortisol levels associated with stress. Ashwagandha is also useful in lowering cortisol levels, as is exercise (9) and other cortisol inhibitors. See treatments for high cortisol, Index/Cortisol inhibitors, Index/Caloric Restriction, Index/Insulin Topics, Index/Glucoregulatory Agents, and Index/Obesity. See measuring hemoglobin A1c to sense long-term glucose intake in the assessment of diabetes risk. A 14% lower risk of type 2 diabetes (adult-onset diabetes) with every 100 mg of supplemental magnesium consumed has been observed. (Diabetes Care 2011 Sep; 34:2116-22; D. Dye, Meta-Analysis Affirms Protective Effect for Magnesium Against Diabetes, Life Extension Magazine, Dec. 2011). See Huseini HF, Larijani B, Heshmat R, Fakhrzadeh H, Radjabipour B, Toliat T, Raza M (2006), The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial, Phytotherapy Research 20 (12): 1036–9.
Taurine in Diabetes Treatment [Links, Papers, Books].
"Taurine supplementation can help prevent the onset of type II diabetes.... Studies have found that having adequate taurine concentrations helps control diabetes by reducing blood glucose and restoring insulin sensitivity. ...Supplementation with just 1.5 grams of taurine daily for just 14 days can reverse diabetes-induced abnormalities in arterial stiffness and improve the ability of the vasculature to respond to changes in blood flow or pressure." - Ian Macleavy (2013), The Forgotten Longevity Benefits of Taurine, Life Extension Magazine, June 2013. Taurine is abundant in fish.
Amyloidosis from insulin amyloid fibrils (based on amylin protein precursors) produced by type II diabetes that kills pancreatic islet beta cells can be treated successfully with nattokinase [US Patent 8137666 B2].
Also, once you have gotten over diabetes, don't forget to reclaim your love life.
 Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. (2003),
Cinnamon improves glucose and lipids of people with type 2 diabetes,
Diabetes Care 2003 Dec;26(12):3215-8.
Dietary Supplements [Longevity Supplement Vendors, Wikipedia, Links, Images, Papers, Patents, Books, Amazon, LifeExtension, Links/Ray Sahelian].
Dilaurylthiodipropionate (an antioxidant) [Links, Images, Video, Papers, Patents, Books], [36s] (c)
DIM Anti-Estrogen Caps (Diindolylmethane) [Links, Images, Video, Papers, Patents, Books]. DIM anti-estrogen caps (diindolylmethane, or 3,3'-diindolylmethane) are used for protection against high estrogen levels, and are described as normalizing estrogen levels. DIM is anticancer, and is derived from the digestion of indole-3-carbinol [Links, Images] found in broccoli, cauliflower, and collard greens. See also Estradiol, Estrogen, Estrogen Protection, and Estrogen Receptors.
DL-Alpha Lipoic Acid [Index/Alpha Lipoic Acid, Telomerase Activators/Alpha Lipoic Acid, Telomerase Activators/Product B/DL-Alpha Lipoic Acid, Links, Images, Video, Papers, Patents, Books, LifeExtension; sources, toxicity, side effects, dosage]. Supplies both Dextro- and Levo-rotary enantiomers of alpha lipoic acid, an antioxidant (ORAC scale). Kumaran S, Savitha S, Anusuya Devi M, Panneerselvam C. (2004), L-carnitine and DL-alpha-lipoic acid reverse the age-related deficit in glutathione redox state in skeletal muscle and heart tissues, Mechanisms of Ageing and Development 2004 Jul;125(7):507-12. Stevens MJ, Obrosova I, Cao X, Van Huysen C, Greene DA (2000), Effects of DL-alpha-lipoic acid on peripheral nerve conduction, blood flow, energy metabolism, and oxidative stress in experimental diabetic neuropathy, Diabetes 2000 Jun;49(6):1006-15. Palaniyappan Arivazhagan, Kadirvel Ramanathan, Chinnakkannu Panneerselvam (2001), Effect of DL-alpha-lipoic acid on mitochondrial enzymes in aged rats, Chemico-Biological Interactions Volume 138, Issue 2, 28 November 2001, Pages 189-198. P Arivazhagan, S Shila, S Kumaran, C Panneerselvam (2002), Effect of DL-alpha-lipoic acid on the status of lipid peroxidation and antioxidant enzymes in various brain regions of aged rats, Experimental Gerontology Volume 37, Issue 6, 1 June 2002, Pages 803-811. Note that DL-alpha lipoic acid is a racemic mixture of R-lipoic acid and S-lipoic acid, and that sodium R-lipoic acid is the most bioavailable form of lipoic acid available, while R-lipoic acid is more bioavailable than S-lipoic acid.
Dimethylsulfoxide (DMSO) [Wikipedia/Dimethyl sulfoxide, Links, Images, Video, Papers, Patents, Books; sources, toxicity]. DMSO represses hTERT transcription. hTERT mRNA levels in the presence of DMSO are used as the null levels in comparative telomerase activator studies by Geron. DMSO, a solvent, causes a garlic-like taste in the mouth when exposed to the skin, although it is of low toxicity and has anti-inflammatory and antioxidant properties.
See DMSO as a drug carrier [Links, Images, Video, Papers, Patents, Books]. DMSO may turn out to be useful in delivering small molecule telomerase inhibitors or activators.
DMAE [Ray Sahelian/DMAE, (dimethylaminoethanol), Wikipedia/DMAE, Links/DMAE, Images, Video, Papers, Patents, Books, LifeExtension/DMAE; Links/DMAE instant face lift, Images, Video, Papers, Patents, Books, LEF; Neck Rejuvenation] (4), (13). DMAE is specified by The Membrane Hypothesis of Aging by Imre Zs-Nagy [Images] to restore cell membrane permeability to potassium, like Centrophenoxine and BCE-001, which are somewhat better for this application. Used for lipofuscin removal (4) and to facilite cell metabolism (13) by rehydrating the cell. DMAE is also used as an "instant face lift".
DNA Damage [Trevigen/DNA Damage, Links/DNA Damage and Aging, Images, Video, Papers, Patents, Books, LibCong, Amazon/DNA Damage and Aging; Links/DNA Damage, Images, Video, Papers, Patents, Books, Amazon/DNA Damage, LifeExtension/DNA Damage; Index/DNA Repair Theory of Aging, SIRT6, Index/Folic acid, Cats Claw Extract, Echinacoside]. (10).
DNA Microarray Analysis [Links, Video, Images, Video, Papers, Patents, Books, Amazon, Glossary of Gene Expression Terms, Index/(Human genes and chromosomes)]. See Shelton DN, Chang E, Whittier PS, Choi D, Funk WD (1999), Microarray Analysis of Replicative Senescence [Index/Replicative Senescence, Links, Images, Video, Papers, Patents, Books, Amazon], Current Biology, 9:939-45. See also Prolla TA (2002), DNA Microarray Analysis of the Aging Brain [Index/Aging Brain, Links, Images, Video, Papers, Patents, Books, Amazon], Chemical Senses, 27:299-306. See Goyns MH, Charlton MA, Dunford JE, et al., (1998) Differential display analysis of gene expression indicates that age-related changes are restricted to a small cohort of genes, Mechanisms of Ageing and Development, 101: 73-90. Also see Lee CK, Klopp RG, Weindruch R, Prolla TA (1999), Gene expression profile of aging and its retardation by caloric restriction, Science, 285: 1130-3 and Miller RA, Balecki A, Shmookler-Reis RJ (2001), Interpretation, design, and analysis of gene array expression experiments, J Gerontol Biol Sci. 56A:B52-7. See also Ramaswamy, S. and T.R.Golub, 2002, DNA microarrays in clinical oncology, Journal of Clinical Oncology 20: 1932-1941, and Hampton, G.M. and H.F.Frierson, Jr., 2003, Classifying Human Cancer by Analysis of Gene Expression, Trends in Molecular Medicine, 9: 5-10.
DNA Nanocircles [Telomolecular Nanotechnologies/nanocircles, Links, Images, Video, Papers, Patents, Books, Amazon]. DNA nanocircles can be produced by a DNA synthesizer [Images]. DNA rolling nanocircle encoding can be used to re-extend telomeres. DNA nanocircles for extending telomeres were invented by Dr. Eric Kool at Stanford University. Rolling nanocircle encoding may be the basis of the ALT mechanism in cancer. (7) Rolling nanocircles should theoretically be available to the cell via using liposomes prepared with cationic transfection reagents and taken up into the cell via liposomal endocytosis. They should be transfected with the same techniques conventionally used for other kinds of DNA plasmid transfection. However, I am not certain that DNA rolling nanocircle technique has been debugged for use in either humans or animals. I note that such plasmids often only last a few weeks inside the cell, so that optimal application might require its use on a repeating basis. DNA circles are found in yeast, where they are involved in cellular aging, but not in normal or senescent human cells. [Leonard Guarente, 2001].
DNA Repair Theory of Aging [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension, Ben Best/DNA Damage and DNA Repair, Wikipedia/DNA Repair, Amazon/DNA Repair, Books/DNA Repair, LifeExtension/DNA Repair, Links/DNA Repair Nutraceuticals, Links/DNA repair enhancement supplements, Links/DNA repair supplements, Books/improving DNA repair, Links/Cat's Claw Extract for DNA Repair, Videos/DNA Repair]. See also DNA repair enhancement: [(10), Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Antioxidants help prevent DNA damage, as do antiglycating drugs and many anticancer drugs and nutraceuticals. "In response to single-strand DNA damage due to:
Elevate SIRT6 for DNA Repair
Fasting with cinnamon, exercise and sirtuin activators such as green tea, quercetin, and resveratrol is probably best for elevating SIRT6, which promotes DNA repair several different ways, improves double-strand DNA repair, rescues homologous DNA repair during cellular senescence, prevents telomere dysfunction, and deflects premature cellular senescence. In addition, SIRT6 has anti-inflammatory and anticancer effect. SIRT1 and SIRT6 should be elevated during anticancer telomerase inhibitition periods, as sirtuin activators tend to condense chromatin, discouraging transcription of protein mRNA and promoting gene silencing.
Echinacoside [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Echinacoside is a phenylethanoid isolated from the stems of Cistances salsa, [Images, Video, Papers, Patents, Books] a traditional Chinese herbal medicine. Echinacoside retards senescence [Images, Video, Papers, Patents, Books]. In addition, echinacoside seems to improve DNA damage protection [Images, Video, Papers, Patents, Books].
DNA Repair Acceleration [Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension].
DNA Repair Cofactors [Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension].
DNA Sequencing Technology [Wikipedia/Full Genome Sequencing, Wikipedia/DNA Sequencing, Wiki/Transmission electron microscopy DNA sequencing, Links/DNA sequencing technology, Images, Video, Papers, Patents, Books, Amazon; Wiki/DNA, Links; Wiki/RNA, Links; SNPs]. DNA sequencing is useful in nucleotide-resolution sequencing of telomeres [Links, Images, Video, Papers, Patents, Books; LifeXLabs/Telomeasures]. DNA sequencing is also useful for decoding genes and chromosomal DNA. See also Genomics. See Sanger sequencing of DNA [Links, Images, Video, Papers, Patents, Books], which is based on enzymatic chain termination of single-stranded DNA to develop a set of variable-sized DNA fragments separable via electrophoresis, and Next-generation DNA sequencing methods [Links, Images, Video, Papers, Patents, Books]. See short-read sequencing [Links, Images, Video, Papers, Patents, Books], new high-throughput sequencing methods [Links, Images, Video, Papers, Patents, Books], and Selena sequencing. DNA sequencing services [Images] include Laragen. DNA sequencing machines [Images] include the ABI Prism 3730 DNA sequencer (Applied Biosystems) and other DNA sequencers [Images]. Halcyon Molecular proposes to use atom-by-atom structural and chemical analysis by annular dark-field electron microscopy to sequence DNA (PDF). Illumina [Images, Video, Papers, Patents, Books] uses reversible terminator-based DNA sequencing by synthesis (SBS) chemistry [Images, Papers, Patents, Books] that images and examines a fluorescent terminator attached to a base before cleaving it off to add the next base while building up a complementary DNA strand. See also DNA pyrosequencing [Images, Video, Papers, Patents, Books], which was developed in 1998, and 4 color DNA sequencing by synthesis [Images, Video, Papers, Patents, Books]. In addition, see Metaphase Spread, automated karyotype analysis [Links, Images, Papers, Patents, Books], Automation of Cytogenetics, Laser Tweezers, Laser MicroDissection, DNA microarrays.
DNA Sequencing Instrumentation - NGS Next-Generation Sequencing
Dopamine [Wikipedia, Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension]. See Dopamine levels and medicines , [11s]. "To increase the amount of dopamine in the brains of patients with diseases such as Parkinson's disease [Index] and dopa-responsive dystonia, L-DOPA, which is the precursor of dopamine, can be given because it can cross the blood-brain barrier." - Wikipedia/Dopamine. Other supplements have been discovered that enhance dopamine levels. DHA improves dopamine levels. Mucuna Pruriens [Links, Images, Papers, Patents, Books] extracted from velvet bean [Images] 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 HGH levels. This happens because dopamine limits hypothalamic somatostatin secretion, resulting in better expression of HGH. Beta-Phenylethylamine (Phenylethylamine) [Links, Images, Video, Papers, Patents, Books, LifeExtension], a metabolite of the amino acid phenylalanine, improves the expression of norepinephrine and increases brain levels of dopamine and serotonin, producing mild euphoria and reducing sensations of pain. See Parkinson's Disease. See also dopamine-uptake inhibitors and deprenyl. Research shows that obese people have smaller brains than normal-weight peers, such that MRI scans show decreasing volumes for obese people in several areas of the brain. Low dopamine levels are associated with the desire to overeat, producing higher levels of obesity and dopamine insufficiency and ever-smaller brain volumes. After Eric R. Braveman, MD, with Dale Kiefer, BS (2011), Combating Age-Related Brain Deterioration, Life Extension Magazine, October 2011. Note that deprenyl, a MAO-B inhibitor that inhibits reuptake of dopamine, reduces lipid peroxidation and aging effects via the ability of dopamine to ligate iron, limiting Fenton reactions that produce hydroxyl radicals. [11s]. Low dopamine is associated with loss of mobility in aging specimens. See Susan Machado (2012), Nutrient 'Cocktail' Delays Aging and Extends Lifespan, Life Extension Magazine, May 2012.
Dopamine Boosters [Links, Images, Video, Papers, Patents, Books, LifeExtension] include:
(1) L-DOPA [Links, Images, Video, Papers, Patents, Books, LifeExtension].
(2) Mucuna Pruriens [Links, Images, Video, Papers, Patents, Books, LifeExtension].
(3) Deprenyl [Links, Images, Video, Papers, Patents, Books, LifeExtension].
(4) DHA [Links, Images, Video, Papers, Patents, Books, LifeExtension].
(5) Beta-Phenylethylamine [Index, Links, Images, Video, Papers, Patents, Books, LifeExtension].
(6) St. John's Wort [Links, Images, Video, Papers, Patents, Books, LifeExtension].
Dosages of Supplements, Optimum [Links, Images, Papers, Books, Amazon], [62s].
Double-strand breaks in DNA [Links, Images, Video, Papers, Patents, Books, Amazon, LibCong, Books/DNA Repair, Amazon/DNA repair, Video/DNA repair, Video/double strand breaks in DNA, Video/DNA repair of double-strand breaks].
Drug Bioavailability [Index/Bioavailability, Wikipedia/Bioavailability, Links, Images, Video/Bioavailability, Papers, Patents, Books, Amazon, LibCong]. Compounds are most likely to be poorly absorbed orally when the molecular weight is > 500, the calculated octanol/water partition is > 5, the number of H-bond donors is > 5, and the number of H-bond acceptors is > 10. (See van de Waterbeemd, Drug Bioavailability.) [83s]. Bioavailability links and Pharmacokinetics with Links/Pharmacokinetics. See The Merck Manual on Bioavailability. See also the journal of Chemical Speciation and Bioavailability, the NIH page on Bioavailability of Nutrients and Supplements. Also see links of The USC Laboratory of Applied Pharmacokinetics and Boomer's Phamacokinetic Resources with A First Course in Pharmacokinetics and Biophamaceutics by David Bourne, PhD.
Drug Design & Discovery [Wikipedia/Drug_design, Links/Drug design, Images, Papers, Patents, Books, LibCong, Amazon; Wikipedia, Links/Drug discovery, Images, Papers, Patents, Books, LibCong, Amazon]. See also Molecular Design Software [Wikipedia, Links, Images, Video, Papers, Books, LibCong, Amazon]. See the index entries for Bioinformatics [Links, Index Entry], Genes [Index], Proteomics [Index], Protocols [Index] and Pathway Analysis [Links, Index Entry] (Biocarta Pathways, SA Biosciences, Promega). For E. Coli protein preparation with cell-free extracts, see [Promega/Protein Expression, Links/Protein Expression]. See also Pharmaceutical Engineering [Wikipedia, Links, Images, Papers, Patents, Books, LibCong, Amazon] and Index Entries/Pharmaceutical Headings, starting with Pharmaceutical Analysis.
Drug Discovery [Wikipedia, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Drugs and Gene Expression [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Supplements and Gene Expression, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Gene Expression, Images, Papers, Patents, Books; Index/Gene, HUGO Gene Families].
Drugs and Ligand Binding [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Supplements and Ligand Binding, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Ligand Binding, Images, Papers, Patents, Books; Index/Gene, HUGO Gene Families].
Drug Interactions [Wikipedia, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon].
Drug Receptors [Index/Receptors, Links/Drug Receptors, Images, Papers, Patents, Books, LibCong, Amazon/Drug Receptors, Books/Drug Design and Transcription Factors, Amazon/Drug Design and Transcription Factors].
Drugs and Transcription Factor Expression [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Supplements and Transcription Factor Expression, Images, Video, Papers, Patents, Books, LibCong, Amazon; Links/Transcription Factors, Images, Papers, Patents, Books; Index/Transcription Factors, Index/Gene, HUGO Gene Families]. Note that sodium butyrate improves the expression of transcription factor Sp1 [List], which causes the expression of the telomerase activator epiregulin, a ligand of the epidermal growth factor receptor (EGFR), to increase dramatically, especially after exercise. Sp1 boosting via sodium buyrate also improves the expression of the hTR component of telomerase, which is under-expressed in mesenchymal-derived tissues such as connective tissues, cartilage, and bone. Note that sodium butyrate, an HDAC inhibitor, is a popular chicken feed that stimulates protein production by expanding chromatin with hyperacetylation, producing bigger chickens with superior characteristics that are relatively immune to cancer. Epidermal Growth Factor (EGF) is another telomerase-activating ligand of the EGFR. I note that EGF seems to produce its telomerase activation by upregulating the transcription factor C-myc, which has more than one site for transcriptional activation in the hTERT promoter. EGF and other telomerase-activating ligands of EGFR may be applied in skin creams.
Dutasteride [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. "Dutasteride belongs to a class of drugs called 5-alpha-reductase inhibitors, which block the action of the 5-alpha-reductase enzymes that convert testosterone into dihydrotestosterone (DHT). Finasteride [LifeExtension, Wikipedia, Links, Images, Video, Papers, Books, Amazon] also belongs to this group." The drug is used to treat enlarged prostate glands from BPH (Benign Prostatic Hyperplasia) and in the treatment of male pattern baldness [74s]. L-Lysine is probably the most inexpensive of the 5-alpha reductase inhibitors, which, when taken with L-arginine, is also a telomerase-activating HGH secretagogue.
Dyskeratosis Congenita (DKC) [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LifeExtension; Medscape/DKC Treatment and Management]. "Dyskeratosis congenita (DKC, Zinsser-Engman-Cole syndrome) is a rare, progressive bone marrow failure syndrome characterized by the triad of reticulated skin hyperpigmentation, nail dystrophy, and oral leukoplakia. Telomerase dysfunction, ribosome deficiency, and protein synthesis dysfunction (are seen) in this disorder. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy." - Medscape/Dyskeratosis Congenita. DKC is estimated to occur in approximately 1 in 1 million people. Dyskeratosis Congenita association with bone marrow failure leading to premature mortality is due to mutations in the genetic code for telomerase template RNA [Images] on chromosome 3q (Vulliamy et al, 2001). Dysfunction of the RNA template component from the hTR gene (hTERC, hTR) leads to dimenished telomerase activity and shorter telomeres (Marciniak and Guarente, 2001). Dyskeratosis congenita (a form of bone marrow failure) is also associated with mutations in exon 6 of TIN2 which often produce short telomeres. Furthermore, Dyskeratosis Congentia seems to some to be due to a mutation in an SP1-binding site on the DKC1 promoter. - after Rüdiger Salowskya, Nina S Heissa, Axel Bennerb, Rainer Wittiga, Annemarie Poustka (2002), Basal transcription activity of the dyskeratosis congenita gene is mediated by Sp1 and Sp3 and a patient mutation in a Sp1 binding site is associated with decreased promoter activity, Gene, Vol 293, Issues 1–2, 26 June 2002, pp. 9–19. It was noticed in connection with DKC that insufficient telomere enlongation accelerates telomere shortening (Mitchell, et al, 1999). See A. Dillon and J. Karlsreder, Cellular vs. Organismal Aging, from K. Lenhard Rudolf (editor), Telomeres and Telomerase in Aging, Disease, and Cancer: Molecular Mechanisms of Adult Stem Cell Ageing, Springer, 2008, p. 10. "The most common form of DC is the X-linked form that is associated with mutations in the DKC1 gene at Xq28 encoding dyskerin," which is part of the telomerase complex. "AD-DC is a rare form of the disease...caused by mutations in the TERC gene located at chromosome 3q26." In some cases of AD-DC, the hTERT gene at 4p15.3 may also be mutated. - H.-Y. Du et al. Telomerase Mutations and Premature Aging in Humans, from K. Lenhard Rudolph (editor), Telomeres and Telomerase in Ageing, Disease, and Cancer, Molecular Mechanisms of Adult Stem Cell Ageing, Springer, 2008. Note that most offspring with the XYY-trait of having all boys in the next generation are apparently healthy, as if essential functions of the X-chromosome are somehow retained and actually genetically viable XYY males are obtained. The segregation of X and Y chromosomal material seems to differ from the Mendelian prediction for karyotype, which would tend to produce more defects than we observe in XYY offspring, which anyway cannot function without retaining the X-chromosome. XYY males [Links] are observed in about 1 in 1000 births, and have the characteristic that they are markedly taller that XY boys. Of these, about 1 in 1000 has a mutation in the X-chromosome for dyskerin leading to Dyskeratosis Congenita, seen in about 1 in 1 million births.
Top Line 99th percentile, Bottom Line 1st percentile (from 400 controls).
In the future, dyskeratosis congenita may be repaired by replacing the mutated DKC1 gene at Xq28 in the patient genome with targeted genome editing using zinc finger nucleases. "The majority of mutations identified to date are missense mutations and are clustered in exons 3, 4 and 11." [REF, PDF]. DKC1 is a large gene starting at 153,991,031 bp from pter and ending at 154,005,964 bp from pter with 36 exons that splices down to just 14,934 base pairs after intron removal. It may be possible to treat dyskeratosis congenita [Patents, Books] with RNA interference plus injections of dyskerin, dyskerin in liposomes absorbed by endocytosis, or with dyskerin from plasmids. Perhaps this is an application for purified nucleoside-modified dyskerin mRNA in liposomes, similar to what has been proposed for hTERT in fast telomere extension.
Dyskerin [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon; Links/dyskerin in telomerase, Images, Video, Papers, Patents, Books; Links/DKC1 promoter, Images, Video, Papers, Patents, Books, Article/DKC1 promoter]. Dyskerin is encoded by the DKC1 gene on the X-chromosome. Dyskerin is a ribonucleoprotein required for correct folding and stability of telomerase RNA (G. Aubert and P. Lansdorp, 2008), and was recently found to be a component of the telomerase complex (Cohen SB, et al., 2007). "Mutations in dyskerin produce dysfunction of telomerase". (Cong, Wright, and Shay, 2002). 2 molecules of dyskerin (25 kDa each), 2 molecules of hTERT protein catalytic component of telomerase, and 2 molecules of telomerase RNA are found in telomerase reverse transcriptase, according to recent research. See Scott B. Cohen, Mark E. Graham, George O. Lovrecz, Nicolai Bache, Phillip J. Robinson, Roger R. Reddel, (2007), Protein Composition of Catalytically Active Human Telomerase from Immortal Cells, Science, 30 March 2007: Vol. 315. no. 5820, pp. 1850 - 1853. "Dyskerin is a component of a small nucleolar ribonucleoprotein (snoRNP) that is highly conserved throughout evolution.... findings indicate that dyskerin plays a role in telomere maintenance by stabilizing TERC." - - H.-Y. Du et al. Telomerase Mutations and Premature Aging in Humans, op.cit. Dyskerin is a potential pseudouridin synthetase that can bind to the H/ACA motif containing snoRNAs (found in retrotransposons) and to the H/ACA motif in hTR. Dysfunctional dyskerin binds to hTR and lowers telomerase transcription rates in dyskeratosis congenita [Index]. - after (W.Klapper, R. Parwaresch, and G. Krupp, 2001, from Mark P. Mattson (editor), Telomerase, Aging, and Disease, p23.) Dyskerin bonds to a motif at a prominent right angle in the folded hTR RNA. Dyskeratosis Congentia seems to be due to a mutation in an SP1-binding site on the DKC1 promoter. - after Rüdiger Salowskya, Nina S Heissa, Axel Bennerb, Rainer Wittiga, Annemarie Poustka (2002), Basal transcription activity of the dyskeratosis congenita gene is mediated by Sp1 and Sp3 and a patient mutation in a Sp1 binding site is associated with decreased promoter activity, Gene, Vol 293, Issues 1–2, 26 June 2002, pp. 9–19. High Sp1 levels should upregulate dyskerin transcription. The dyskerin gene DKC1 is also upregulated by c-Myc. See Faizan Alawi, Megan N. Lee (2007), DKC1 is a direct and conserved transcriptional target of c-MYC, Biochemical and Biophysical Research Communications, Vol 362, Issue 4, 3 Nov 2007, pp 893–898.
Note that if dyskerin is located on the X-chromosome, XYY karyotype males might benefit from an added dyskerin gene put in with plasmids, viral vectors, or zinc finger nuclease technology to replace the defective mutated form of the dyskerin gene. See telomere repair in XYY-karyotype males [Images, Papers, Patents, Books]. Telomerase may still function rather well in XYY-karyotype males, but with less hTR stability if dyskerin is mutated (1 in 1000000 total births). See Dyskeratosis Congenita in XYY-karyotype males, X-linked Dyskeratosis Congenita, and bone marrow failure in Dyskeratosis Congenita. See also Index/Gene to examine other genes confined to the X-chromosome. Also see She Male Longevity for Crossing Sex Karyotypes.
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