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NAD Synthesis [Index/NAD+, Life Enhancement/NAD Synthesis and Life Extension, (nicotinamide adenine dinucleotide), Patents/NAD in treatment, Links/NAD, Wikipedia/NAD; LifeExtension/NAD; Links/NAD supplements, Images, Papers, Patents, Books; Links/NAD synthesis, Images, Papers, Patents, Books, LifeExtension/NAD synthesis; Links/NAD toxicity; 6s]. "NAD+ (Nicotinamide Adenine Dinucleotide) is essential for many key metabolic reactions and in most organisms there are two parallel pathways for its biosynthesis. NAD is synthesized de novo from typtophan [Images] and recycled from nicotinamide via the NAD+ salvage pathway." - Haim Y. Cohen, Keven J. Bitterman and David A. Sinclair, Metabolic Regulation of Gene Silencing and Lifespan, from Aging at the Molecular Level, edited by Thomas von Zglinicki, Kluwer, 2003, p.202. With regard to human fibroblast telomere shortening experiments, "Continuous treatment with nicotinamide, which led to lower ROS generation and changes in mitochondrial function, has been reported to extend lifespan (a remarkable 1.6-fold increase) and decelerate telomere shortening (Kang, et al., 2006)." from Telomeres and Telomerase in Ageing, Disease, and Cancer: Molecular Mechanisms of Adult Stem Cell Aging, ed. K. Lenhard Rudolph. See Kang HT, Lee HI, Hwang ES (2006), Nicotinamide extends replicative lifespan of Human Cells, Aging Cell, 5(5): 423-36. See Links/Neutraceutical Sources of Nicotinamide, Links/Sources of Nicotinamide and Images/Nicotinamide Supplements. However, note that "Nicotinamide (NAM, niacinamide) was recently demonstrated to be a strong inhibitor of yeast SIR2 and human SIRT1 activity, both in vitro and in vivo. We found that cells grown in the presence of this compound showed nearly complete loss of SIR2-dependent silencing." - - Haim Y. Cohen, Keven J. Bitterman and David A. Sinclair, Metabolic Regulation of Gene Silencing and Lifespan, from Aging at the Molecular Level, edited by Thomas von Zglinicki, Kluwer, 2003, p.204. Note that NAD+ is a substrate for tankyrase 1, which removes TRF1 binding protein from telomere t-loops, allowing them to open and become accessible to telomerase when telomeres are short < 20 kbp (De Lange, et al, 2001: US Patent No. 6,277,613 B1, Aug. 21, 2001). Continuous expression of tankyrase 1 results in telomere lengthening. Tankyrase 1 may be phosphorylated by insulin for this reaction. Note that NAD+ is required as substrate for generating ADP-ribose monomers for poly(ADP-ribo)sylation by a PARP [poly(ADP-ribose) polymerase] enzyme like tankyrase 1. - Wikipedia/Poly_ADP_ribose_polymerase. 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 NAD every other day, or perhaps as much as 5 mg every other day. At higher levels, stomach upset is sometimes observed.
NADH, NAD+, and Vitamin B3. Note that vitamin B3 is niacin [Smart-drugs/IAS-NADH, LEF/vitamin B3, Links, LibCong/vitamin B3, Links/niacin, Links/NADH; Links/NAD]. Niacinamide (nicotinamide), and other related chemicals are sometimes sold as niacin. Niacinamide (nicotinamide) is a SIRT1 inhibitor that is eventually converted to NAD+, a SIRT1 activator, by a NAD+ synthesis salvage pathway. See NAD synthesis. Note that Nicotinamide Adenine Dinucleotide is NAD+. NADH [Images] is not the same molecule, but includes an extra atom of hydrogen. The reaction between them is
Thus Nicotinamide Adenine Dinucleodide (NAD+) acts as a carrier of electrons in oxidation-reduction reactions by accepting electrons (e-) to form NADH. NAD+ is a coenzyme that works together with enzymes to improve reaction rates. Nicotinamide riboside [Index, Images, Papers, Patents, Books] is a form of vitamin B3 boosting levels of NAD+. See Scott Rahway (2014), The Youth Restoring Benefits Of NAD+, Life Extension Magazine, November 2014.
Nanomedicine [Wikipedia/Nanomedicine, Links/Nanomedicine, Images, Video, Papers, Patents, Books, Amazon, LibCong/Nanomedicine, LifeExtension; Links/Nanotechnology, Images, Video, Papers, Patents, Books, Amazon, LibCong], [76s]. Problems for Nanotechnology (Video). See nanoprocessing for particulates [Images], nanofabrication for particulates [Images], and nanofabrication to improve drug bioavailability [Images].
Nanoparticulates in Drug Delivery [Links, Images, Video, Images, Papers, Patents, Books, LEF, LibCong/Nanoparticuluates, Amazon; Links/Nanoencapsulation, Images, Video, Papers, Patents, Books, LEF]. Nanoencapsulation has been used to increase the bioavailability of curcumin dramatically.
Nanotechnology Drug Delivery [Links, Images, Video, Papers, Patents, Books, LifeExtension, LibCong, Amazon].
Naringin [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Naringin, which gives grapefruit its bitter taste, extends the half-life of circulating drugs [Images, Papers, Patents, Books]. Naringin is highly concentrated in grapefruit and is also abundant in oranges. Perhaps it can be used to extend the half-life of certain specific telomerase activators, such as Nitric Oxide. Check. Naringin is often taken with fat burners such as green tea extract (EGCG) and caffeine.
Natto [Wikipedia/Natto, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Natto (a fermented soy) is the best food source of vitamin K2, better than Swiss Cheese. According to rumors (check), it is best taken covered with honey, and is about the only nutraceutical cure for aortic sclerosis, the condition preceeding aortic stenosis resulting from systemic calcification [Papers, Patents, Books].
Nattokinase [Wikipedia/Nattokinase, Links, Images, Video, Papers, Patents, Books, LifeExtension]. Nattokinase is able to prevent and dissolve a broad spectrum of amyloidosis amyloid fibrils, including transthyretin amyloid fibrils, amyloid beta amyloid fibrils, prion amyloid fibrils, insulin amyloid fibrils, and beta-microglobulin fibrils. Nattokinase helps dissolve abnormal blood clots that can cause heart attacks and strokes, and conditions such as phlebitis, pulmonary embolism, or deep vein thrombosis. Rita P.-Y. Chen, Kung-Ta Lee (2012), Nattokinase for degrading and reducing amyloid fibrils—associated with alzheimer's disease, prion diseases and other amyloidoses [OnLine], US Patent 8137666 B2, Published March 20, 2012. Technically, nattokinase is not a kinase with a mission to phosphorylate, but a serine protease in the subtilisin family exhibiting strong fibrolytic activity.
Natural Products Association [Site, Links, LibCong]. TA-65 is certified by the Natural Products Association.
Neck Rejuvenation [Refs11, Links/Neck rejuvenation, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon; Links/Exercises for Neck rejuvenation, Images, Video, Papers, Patents, Books, LifeExtension; Links/Facial Exercises, Images, Video, Papers, Patents, Books; Shape Your Face Facial Exercises: Shape Your Face - Exercise 4; Platysma exercises, Sternomastoid exercises; How to remove a double chin (Images, Video); Improve hTR expression in connective tissue with Sp1; Links/Platysmal banding, Images, Papers, Patents, Books, LifeExtension; Adipocytes; Results/Plastic Surgery for Neck Rejuvenation; Index/Facial Anatomy; Links/How to Define Your Neck, Images, Video, Papers, Patents, Books; Links/Neck Tightening, Images, Video, Papers, Patents, Books; Links/Neck Creams, Images, Video, Papers, Patents, Books, LifeExtension; SeroVital; Oral phytoceramides; Anti-collagenase, Anti-elastase Extracts].
Orally bioavailable phytoceramides inhibiting elastase and making up for lost skin ceramide production as aging proceeds are associated with dramatic facial rejuvenations including wrinkle reduction and neck rejuvenation.
Tape It Up - Disguising the Problem
Pulling the skin of the neck tightly backwards with both hands typically removes platysmal banding, and a single piece of tape pulling both sides of the neck back at the same time has the same effect. The tape can be hidden under a necktie and collar, or under a ladies neck band, or under a turtleneck sweater or turtleneck top shirt. George Washington's ghost suggested while I was in the shower that white surgeon's tape was used during the American Revolution for taping up the neck, and that it sometimes cured platysmal banding after several days. I found that a band of white surgeon's tape applied clear around the neck can make the neck look tight immediately, though it resembles a Catholic priest's collar to many casual witnesses, who take you for a priest. The white tape can be concealed under a turtleneck, neckwrap, or sweater then. Pulling the skin back all around the face for a total facelift produces The Flying Nun look.
Old Neck Wear
For a quick fix, see tight turtleneck sweaters, and high turtleneck sweaters ... of deep forest green. Horse's necks are sweated with a wrap [Images] to improve the looks of their necks, and there is a sweat wrapping with a velcro fastener for a horse's neck and jowls, too. You can tape your neck up with surgeon's paper tape or masking tape to implement a sweat wrap, and it can be worn all night. This might be applied to humans prior to neck exercise, general exercise, or a sauna. Keeping the water out, or using a diuretic such as caffeine or theobromine (found in cocoa) to reduce water may also be useful or necessary to maintain a dry, tight, sweated-out look.
Old Neck Exercises
The platysma muscle needs to be tightened up under the chin to prevent a sagging neck. This is done by
A useful related exercise is to thrust the lower jaw forward and tense the neck in a way that stretches everything perfectly flat, without cords of tissue coming out, repeatedly. This also works for the previous exercise in which the head goes back over one shoulder. The neck can be lubricated with extra virgin olive oil or skin-tightening colostrum solution and the fingers and palm can be used to press tissue down flat against tensing muscles. Pressing the tongue against the roof of the mouth tenses the platysma muscles. Many sets of these tissue-flattening exercises seem to yield a flattened neck without unusual cords of tissue muscle, and gets superior results more rapidly. Best results are obtained if the neck exercises are done 2-3 times per day, and in combination with a diet (say tuna or salmon on soda crackers, fresh raw pineapple, apples, onions with sauce on crackers, and cooked carrots with green or black tea) to eliminate submental fat associated with adipocytes and adipose tissue under the chin.
Tissue Shape Training
Lubricating the neck with extra virgin olive oil and brushing platysmal banding structures backwards away from the Adam's apple of the neck while flexing in a way that flattens the neck seems to brush fat cells backwards. After 1.5 hours of this, the appearance of the neck is improved considerably. One must rest between sets for a minute or two every 3 or 4 minutes after patting the structure down. This is rigorous training that is tiresome, but it does have some positive effect. A single 1.5 hour application visibly helps, but several applications may be required for the most durable finished results. Emphasizing grapefruit in the diet at the same time to activate AMPK with nootkatone helps eliminate problem fat cells. Salmon is best for favorable DHA and EPA fatty acids during such a diet, a fine source of taurine and protein, and is superior to meat and poultry for obtaining definition and eliminating traces of obesity.
Bull Neck Option
Recently I have noticed that old folks with big muscular bull necks suffer less from turkey wattle and so forth, so now I do neck raises on the edge of a bed with dumbell plates on my forehead over a towel. Increase the weight as time goes on. This gets the number of reps down in the neck raise, and might cause cramps at first. Note that removal of submental fat by caloric restriction and seeking muscular definition helps. In combination with a diet, neck exercise really does seem to work to fix platysmal banding.
Old Neck Surgery
"Turkey wattle removal [Images, Video, Papers, Patents, Books] may also be in order. Cervicoplasty [Images, Video, Papers, Patents, Books; Refs11/Plastic Surgery] is a surgical procedure that removes excess or loose skin from the front of the neck. It involves a small incision below the chin and perhaps behind the ears. The excess skin is then neatly trimmed and tightened up. The results of this simple procedure can last over ten years, at which point a touch up may be needed. During the surgery excess fat may also be removed with a suction device - liposuction. All this will sharpen up the chin and jawline, taking years off a person's appearance." - from Shape Your Face - Exercise 4.
Skin Cream Elements for the Old Neck
See Skin, Hexapeptide 10 (Serilesine), Matrixyl 3000, and Growth Factor Skin Creams, which can be used to restore collagen and elastin in the skin, and even integrins and hemidesmosomes with hexapeptide 10. "Due to aging, ultraviolet light, and environmental exposures, the skin of the neck is highly susceptible to the visible signs of aging. Advanced topical nutrients such as
SeroVital [Links], an HGH secretagogue, is also available as a neck rejuvenation cream. Although HGH secretagogues stimulate the pituitary gland, the nitric oxide from arginine in transdermally applied SeroVital should dialate vessels in the skin with vasodilator effect, making tissue in that region more available for HGH, an endocrine hormone circulating in the blood.
Connective Tissue Integrity and hTR Expression
Note that the failure of connective tissue seems to be an issue in neck aging. In adult tissues, hTR is present and most highly expressed in the spermatocytes and Sertoli cells of the testis, moderate expression is observed in germinal center lymphoid follicles, and weak expression is present in regenerative cellular epithelia, but is not seen in the nervous system and mesenchymal derived tissues including connective tissue, bone, cartilage, and the circulatory system and lymphatic system cells. See hTR and the hTR Promoter.
Expression of hTR in adult tissues is predominantly limited to dividing cells, although certain differentiated postmitotic cells express hTR. [Yashima K, Wright WE, Shay JW, et al., 1998, Papers/hTR activation, Papers/small molecule hTR activators, J. Zhao, et al, 2003, Links/telomerase RNA gene activation, Links/hTR plasmids, Links/hTR transfection]. The hTR or hTERC promotor is silenced via methylation [Index, Links, Papers]. Sp1 (binding at GC boxes) and HIF-1 are positive regulators of hTR transcription (C.J. Cairney and W.N. Keith, 2007). Note HIF-1 can be upregulated by hypoxia from exercise, ginkgo biloba, or by fenugreek seed, while Sp1 is upregulated by sodium butyrate [Images] and down-regulated by insulin deprivation. Perhaps these can be applied to solve the special problems involving mesenchymal-derived tissues. Sodium butyrate supplements are sometimes shown with a rooster-waggle neck picture, probably to suggest that they may be good for neck wattles composed of old connective tissue derived from mesenchymal cells by boosting the expression of hTR there via elevated Sp1. Increased Sp1 binding to promoter regions is seen in cells that overexpress the endogenous antioxidants Cu/Zn-SOD (SOD1) and/or catalase [Index], and curcumin has been observed to increase Sp1 binding.
Also see Gary Goldfaden, M.D., and Robert Goldfaden (2013), Revitalize Your Aging Neck, Life Extension Magazine, April 2013 [Refs11b]. Other recommended ingredients of topical formulations for the aging neck include:
Nerve Growth Factor [Wikipedia, Links/Nerve Growth Factor, Images, Video, Papers, Patents, Books, LifeExtension; Links/the Nerve Growth Factor promoter, Images, Papers, Patents, Books; Links/supplements boosting Nerve Growth Factor, Images, Papers, Patents, Books, LifeExtension]. Nerve Growth Factor (NGF) is elevated by:
Nervous breakdown [Links, Papers, Patents, Books, LifeExtension; Links/stress-induced nervous breakdowns, Links/drug-induced nervous breakdowns; Links/psychosocial stressors], . Sometimes nervous breakdowns are due to stress, stemming from high levels of cortisol originating in stress. Cortisol inhibitors [Index] such as ashwagandha are useful in managing this type of nervous breakdown. Also see adaptogens such as Rhodiola Rosea. Antidepressants may be useful. Sometimes too-frequent use of drugs or intoxicants results in symptoms of nervous breakdown or nervous exhaustion. The phenothiazine family of drugs such as thorazine (chlorpromazine) are sometimes used as tranquilizers to manage cases including confusion or hallucinations.
Nettle Root Extract [Links/Nettle Root Extract, Images, Papers, Patents, Books, LifeExtension]. Nettle root helps protect prostate cells [Links, Images, Papers, Patents, Books] against growth stimulatory effects of estrogen [Links, Books], which is produced more from testosterone in men as they age. See Prostate Cancer and Benign Prostatic Hyperplasia.
Neurobiology of Aging [Journal, Links/Neurobiology of Aging, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension] on-line. See Acetyl L-Carnitine, Alpha Lipoic Acid, Alzheimer's Disease, Amyloid Beta, Anti-Inflammatory Nutraceuticals, Antioxidants, Ashwaganda, Atherosclerosis, Atherosclerotic Plaque, Bacopa, Benfotiamine, Brain, Brain Cancer, Brain Deterioration, Brain Growth and Development, Benfotiamine, Cellular Senescence, Centrophenoxine, Cognitive Decline, CoQ10, Curcumin, DHA, DMAE, Dementia, Endogenous Antioxidants, Free Radical Theory of Aging, HGH, Hypoperfusion, Leukoaraiosis, Lewis Bodies, Lipofuscin, Luteolin, Membrane Hypothesis of Aging (4) (13), Membrane Integrity, Metal Ions, Mitochondrial Aging, Mitochondrial Biogenesis, Myelin Sheath, NAD+ Biosynthesis, Nerve Growth Factor, Nervous Breakdown, Neurochemistry, Neurodegenerative Disorders, Neurological Aging, Neurology, Neuropathy, Neuroprotective Supplements, Neuronal Regeneration, Neurofibrillary Tangles, Neurological Aging, Parkinson's Disease, PQQ, Resveratrol, ROS, SIRT1, SOD, Stroke, TNF-alpha, Tocotrienols, Ubiquinol, Vitamin D, Vitamin K2, and Vitamin E. 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, Papers, Patents, Books]. See Preventing axonal degeneration in nerve cells [Images, Papers, Patents, Books]. 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 that condenses chromatin. This fact should be directly related to optimal dosages of NAD+. Ray Sahelian promotes 2.5 mg of NADH every other day, or perhaps as much as 5 mg every other day. At higher levels, stomach upset is sometimes observed.
Neurochemistry & Neurochemistry of Aging [Links/Neurochemistry, Images, Video, Papers, Patents, Books, LibCong, Amazon; LifeExtension/Neurochemistry of aging, Links, Images, Video, Papers, Patents, Books].
Neurodegenerative Disorders [Wikipedia/Neurodegenerative Diseases, Links/Neurodegenerative Diseases, Images, Papers, Patents, Books, LibCong, LifeExtension, Amazon; Links/Neurodegenerative Disorders, Images, Papers, Patents, Books, LibCong, LifeExtension, Amazon] and medicines . See index entries for Acetyl L-Carnitine, Alpha Lipoic Acid, Alzheimer's Disease, Amyloid-Beta, Amylotrophic Lateral Sclerosis (ALS), Ashwaganda, Atherosclerosis, Bacopa, Benfotiamine, Brain Cancer, Brain Degeneration, Cognitive Decline, Dementia, Fisetin, Green Tea, Hypoperfusion, Leukoaraiosis, Lutein, Memory Enhancing Nutraceuticals, Microglial Activation, Microglial Senescence, Myelin Sheath, Neurobiology of Aging, Neuropathy, Neuroprotective HGH, Parkinson's Disease, Parsley, Sage, Rosemary and Thyme, Stroke, TNF-alpha, and Tocotrienols. 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 every other day, or perhaps as much as 5 mg every other day. At higher levels, stomach upset is sometimes observed. Supplements "...with anti-inflammatory actions protect against neurodegenerative diseases ..." See Susan Machado (2012), Nutrient Cocktail Delays Aging and Extends Life Span, Life Extension Magazine, May 2012. Tocotrienols inhibit neurogeneration. see Thomas Rosenthal (2014), Little-Known Benefits of Tocotrienols, Life Extension Magazine August 2014. Green tea can restore hippocampal neurons and defends against Alzheimer's Disease. See Michael Downey (2014), How Green Tea Protects Against Alzheimer’s Disease, Life Extension Magazine, August 2014. Green tea can restore hippocampal neurons. Note that the senescence of microglial cells leads to failure of amyloid beta clean-up operations and produces Alzheimer's Disease unless telomerase activators are used to remedy the cellular senescence of hemopoietic stem cell precursors of the microglial cells.
 Bastianetto S, Brouillette J, Quirion R. (2007), Neuroprotective effects of natural products: interaction with intracellular kinases, amyloid peptides and a possible role for transthyretin, Neurochem Res 2007 Oct;32(10):1720-5. N
Neuroprotective nutraceuticals: [Links, Papers, Patents, Books, LifeExtension].
 Dragicevic N, Smith A, Lin X, et al. (2011), Green tea epigallocatechin-3-gallate (EGCG) and other flavonoids reduce Alzheimer’s amyloid-induced mitochondrial dysfunction, J Alzheimers Dis 2011;26(3):507-21.
 Cai D (2013), Neuroinflammation and neurodegeneration in overnutrition-induced diseases,
Trends Endocrinol Metab 2013 Jan;24(1):40-7.
Neuroendocrine Theory of Aging [IAAS/Neuroendocrine Theory of Aging, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension], [19s].
Neurofibrillary tangles [Wikipedia, Links/Neurofibrillary tangles, Images, Video, Papers, Patents, Books, Amazon, LifeExtension]. Consider neurofibrillary tangles and cognitive decline [article, Books/treating old age cognitive decline, Links/old age cognitive decline]. Neurofibrillary tangles can arise from aluminum poisoning and are also seen in Alzheimer's Disease. Aluminum is chelated by curcumin. See Dementia. The formation of neurofibrillary tangles can be inhibited by grape seed extract. See Michael Downey (2013), Uncovering the Broad-Spectrum Protection of Anthocyanins, Life Extension Magazine, July 2013.
Neurological Aging [Links/Neurological Aging, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension; Memory Enhancing Nutraceuticals, Neuroprotective HGH]. Acetyl L-carnitine with alpha lipoic acid counteracts neurobiology of aging, as do other medicines that elevate Nerve Growth Factor. Ashwagandha and Bacopa, which both elevate the endogenous antioxidants SOD, catalase, and glutathione, are also useful in counteracting neurological aging and in lowering stress-related cortisol and elevating levels of the neurotransmitter acetylcholine. Melatonin (taken before bedtime) boosts levels of glutathione peroxidase. Benfotiamine increases nerve impulse velocities. 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 every other day, or perhaps as much as 5 mg every other day. At higher levels, stomach upset is sometimes observed.
 Salthouse TA (2009),
When does age-related cognitive decline begin?, Neurobiol Aging 2009 Apr;30(4):507-14.
Neurology [Links, Video, Papers, Books, LibCong, Books/Anti-Aging Neurology, Books/Clinical Neurology, Amazon/Neurology, Amazon/Clinical Neurology].
Neuronal Regeneration [Wikipedia/Neuroregeneration, Links, Images, Video, Papers, Patents, Books, LibCong/Neuroregeneration, Amazon, LifeExtension; Links/Neuronal Regeneration, Images, Video, Papers, Patents, Books, LibCong/Neuronal Regeneration, Amazon, LifeExtension]. See Julius Goepp, MD, Preserving Cognitive Function with Aging, Life Extension Magazine, and related articles and videos, Papers, Patents, Books, (Videos/Cognitive Function and Aging). Also see
Neuroscience [Links, Video, Books, LibCong/Neuroscience, Amazon, Books/Neuroscience of Aging, LibCong/Neuroscience of Aging, Links/Aging and Neuroscience, Images, Papers, Patents, Books, Recent articles].
Neygeront [IAAS/Neygeront, Links], as a supplement, about $50 for 40 capsules, , (1).
NFκB (NF-kB, Nuclear Factor Kappa Beta) [Wikipedia/NF Kappa Beta, LEF/NFκB, Links, Images, Video, Papers, Patents, Books, LibCong/Nuclear Factor KB, Amazon, LifeExtension]. Nuclear Factor Kappa Beta is an inflammation activator (an inflammatory cytokine or proinflammatory cytokine) associated with old-age diseases that is found in every cell type. [68s]. It has been implicated along with TNF-alpha (Tumor Necrosis Factor alpha) as a factor in focal tissue remodeling in cancer. Both inflammatory cytokines are generated by senescent cells as a consequence of senescent cell gene expression [Images, Papers, Patents, Books]. See Anti-inflammatory Nutraceuticals. Both Nuclear Factor Kappa Beta and TNF-alpha may behave like tumor promoters for ROS-induced DNA damage (10) provided by free radical tumor initiators or for DNA damage introduced by carcinogens. Both TNF-alpha and NF-kB are telomerase activators opposing anticancer telomerase inhibitors and so are associated with tumor promoter effects if maintained at high levels for a long time. NF-kB is a transcription factor upregulating genes for inflammatory cytokines eventually leading to cancer. Furthermore, NF-kB stimulates production of apoptosis inhibitors sustaining cancer cells and increases the expression of gene products associated with cancer cell proliferation, invasion, metastasis, and tumor angiogenesis. Furthermore, NF-kB promotes the survival of cancer stem cells. Genes promoted by NF-kB include:
"Incorrect regulation of NF-kB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development." - Wikipedia.
NF-kB has been implicated in 95% of human cancers. See David Hoffnung (2011), The Inflammatory Factor Underlying Most Cancers, Life Extension Magazine, November 2011. NF-kB has a central role in the development of breast cancer, perhaps emanating from failure to drain breasts of milk until inflammation develops. See Liu M, Sakamaki T, Casimiro MC, et al. (2010), The canonical NF-kappaB pathway governs mammary tumorigenesis in transgenic mice and tumor stem cell expansion, Cancer Research, 2010 Dec 15; 70(4):10464-73. See also Prasad S, Ravindran J, Aggarwal BB (2010), NF-kappaB and cancer: how intimate is this relationship, Molecular and Cellular Biochemistry, 2010 March; 336(1-2):25-37. Pikarsky E, Porat RM, Stein I, et al. (2004), NF-kappaB functions as a tumour promoter in inflammation-associated cancer, Nature, 2004 Sept 23; 431(7007):461-6. Weisz L, Damalas A, Liontos M, Karakaidos P, Fontemaggi G, Maor-Aloni R, Kalis M, Levrero M, Strano S, Gorgoulis VG, Rotter V, Blandino G, Oren M (2007), Mutant p53 enhances nuclear factor kappaB activation by tumor necrosis factor alpha in cancer cells, Cancer Research 76:2396-2401. More than 50% of human cancers feature mutation of p53.
NFkB Inhibitors [Index/NFkB, Links, Images, Papers, Patents, Books, LifeExtension].
NFkB inhibitors which also serve as cancer metastasis inhibitors and CR-mimetic nutraceuticals include:
NF-kB inhibitors derived from spices [Ref] include:
NF-kB inhibitors useful for anticancer applications also include:
 David Hoffnung (2011),
The Inflammatory Factor Underlying Most Cancers, Life Extension Magazine, Nov 2011.
 Pikarsky E, Porat RM, Stein I, et al Y. (2004),
NF-kappaB functions as a tumour promoter in inflammation-associated cancer,
Nature 2004 Sep 23;431(7007):461-6.
 Van der Heiden K, Cuhlmann S, Luong le A, Zakkar M, Evans PC (2010),
Role of nuclear factor kappaB in cardiovascular health and disease,
Clin Sci (Lond) 2010 Feb 23;118(10):593-605.
Niacin See Vitamin B3, Niacinamide, and Nicotinamide.
Nicoplex [Links/Nicoplex, Images, Papers, Patents, Books, Nicoplex Patent], a DNA repair enhancer [Links, Papers, Patents, Books, (10)]. Nicoplex is composed of carotenoids, zinc, and nicotinamide. See Sheng Y, Pero RW, Olsson AR, Bryngelsson C, Hua J., 1998: DNA repair enhancement by a combined supplement of carotenoids, nicotinamide, and zinc, Cancer Detection and Prevention, 1998;22(4):284-92. The patent for Nicoplex also includes water-soluble Uncaria Tomentosa [Images] species extract (Cat's Claw extract) in the formulation.
Nicotinamide (Niacinamide) [Links/extends replicative lifespan of human cells, Links/nicotinamide, Images, Video, Papers, Patents, Books, Links/nicotinamide supplements, Images/nicotinamide supplements, Amazon, LibCong/Nicotinamide, Life Extension/nicotinamide]. With regard to human fibroblast telomere shortening experiments, "Continuous treatment with nicotinamide, which led to lower ROS generation and changes in mitochondrial function, has been reported to extend lifespan (a remarkable 1.6-fold increase) and decelerate telomere shortening (Kang, et al., 2006)", from Telomeres and Telomerase in Ageing, Disease, and Cancer: Molecular Mechanisms of Adult Stem Cell Aging, ed. K. Lenhard Rudolph. See Kang HT, Lee HI, Hwang ES (2006), Nicotinamide extends replicative lifespan of Human Cells. Also see Kang HT, Hwang ES (2009), Nitotinamide enhances mitochondria quality through autophagy activation in human cells, Aging Cell 8, 426-438.
Note that nicotinamide is processed to produce NAD+, the substrate used by tankyrase 1 [Index] to poly(ADP-ribo)sylate TRF1 to strip it from the telomere, allowing the telomere t-loop to open for access by the telomerase holoenzyme. I take it in the morning, to generate NAD+ by the time I take telomerase activators at night, including Fenugreek extract just before bedtime (1-2 grams). This is done during two weeks of telomerase activation. Nicotinamide (Niacinamide) produces inhibiting effects on PARP enzyme, so I avoid putting it in other than in the mornings, taking 1-2 grams during 2-week telomerase activation periods followed by 2-week telomerase inhibition periods. On the other hand, NAD+ (NADH) from nicotinamide is an essential substrate for the tankyrase 1 reaction. NAD+ may be taken at 2.5 mg every other day to keep its level sufficiently high. Note that nicotinamide boosts tankyrase 1 levels. Furthermore, nicotinamide is a SIRT1 inhibitor, so that it tends to oppose SIRT1 gene silencing, keeping chromatin expanded for transcriptional activity. See vitamin B3.
Nicotinamide Riboside [Links/Nicotinamide Riboside, Images, Video, Papers, Patents, Books; Supplements]. Nicotinamide riboside is a metabolic precursor for nicotinamide mononucleotide [Links, Images, Video, Papers, Patents, Books] and NAD+. It is useful for rejuvenating mitochondria. See mitochondrial themes starting with mitochondrial biogenesis. Nicotinamide mononucleotide (NMN) via nicotinamide riboside manifests regenerative effects on cells and mitochondria by affecting sirtuin proteins. "Normal metabolisis of Niacin also produces other compounds, some of which appear to have effects opposed to those of NMN. This means that simply taking in much more Niacin will not have the same effect as increasing NMN intake" - Koen. See vitamin B3. See also Scott Rahway (2014), The Youth Restoring Benefits Of NAD+, Life Extension Magazine, November 2014. Note that simple nicotinamide itself is very life-extending and boosts NAD+ expression.
NAD+ retards aging [Papers, Patents, Books]. Note that NADH is also available as a supplement for boosting life-extending and neuroprotective NAD+. See also
 Pawel Bieganowski and Charles Brenner (2004),
Discoveries of Nicotinamide Riboside as a Nutrient and Conserved NRK Genes Establish a Preiss-Handler Independent Route to NAD in Fungi and Humans [PDF]
Cell, Vol. 117, 495–502, May 14, 2004.
 Yang T, Chan NY, Sauve AA (2007),
Syntheses of nicotinamide riboside and derivatives: effective agents for increasing nicotinamide adenine dinucleotide concentrations in mammalian cells,
J Med Chem 2007 Dec 27;50(26):6458-61.
 Scott Rahway (2015),
“Next Generation” Vitamin Provides Hope To Aging Societies Worldwide,
Life Extension Magazine Jan 2015.
Nicotine [Links, Images, Video, Papers, Patents, Books; Nictotine as a telomerase activator; Fatal dose of Nicotine]. As a telomerase activator, nicotine lengthens telomeres in vascular endothelial cells. Nicotine is also an anti-inflammatory HMGB1 inhibitor. Nicotine overdose was rumored to thrill, then put sufferers to sleep when given as a fatal dose (check).
Nitric Oxide [Telomerase Activators/Nitric Oxide, Links/Nitric Oxide, Images, Video, Papers, Patents, Books, LibCong/Nitric Oxide, LifeExtension; Links/Nitric Oxide Supplements, Images, Papers, Books, LifeExtension; Links/Nitric Oxide Stacks, Images; The journal Nitric Oxide]. Nitric Oxide is a telomerase activator acting on endothelial progenitor cells and very useful as a vasodilator. Nitric oxide activates telomerase [Vasa, et. al, 2000; Hayashi, et.al, 2006, Haendeler, 2006] in the endothelial cells of the vascular system, and promotes mitochondrial biogenesis [Links, Images, Papers, Patents, Books]. See also nitric oxide in mitochondrial function [LifeExtension, Books], . Generation of nitric oxide (NO) may act as a unifying molecular switch to trigger the whole mitochondrial biogenesis process. See Nisoli E, Carruba MO (2006), Nitric oxide and mitochondrial biogenesis [Abstract], Journal of Cell Science 2006 Jul 15;119(Pt 14):2855-62. Nitric Oxide (NO) production is stimulated by:
See NO More Heart Disease by 1998 Nobel Prize winner Louis Ignarro [Video].
NK Cells (Natural Killer Cells) [Wikipedia, Links/Natural Killer cells, Images, Video, Papers, Patents, Books, LifeExtension]. Natural Killer cells attack and consume senescent cells showing proinflammatory status or signs of oncogenic stress [William Falloon, Jan 2015; Campos C, et al, July 2014]. Astragalus and astragaloside supplements preferentially lengthen Natural Killer (NK) cell telomeres, ensuring NK cell availability at higher number densities. Lipoic acid elevates cAMP in NK cells to lover caveolin-1 (gene CAV1) levels and oppose NK cell senescence . This is also true of TA-65. The issue of whether to replace senescent cells or reverse their senescence is impacted by this insight, as astragalus and a few other supplements lead to increased NK cell activity that consume dangerously inflammatory senescent cells. NK cells also attack various pathogens and virus-infected cells.
 Schillace RV, Pisenti N, Pattamanuch N, et al. (2007),
Lipoic acid stimulates cAMP production in T lymphocytes and NK cells,
Biochem Biophys Res Commun 2007 Mar 2;354(1):259-64. Index/cAMP.
NMR Spectroscopy [Wikipedia, Links, Images, Video, Papers, Patents, Books, LibCong, Amazon]. See Instrumental Analysis.
Non-alcoholic Fatty Liver Disease [Links, Images, Video, Papers, Patents, Books, LifeExtension]. Non-alcoholic fatty liver disease, the liver's manifestation of metabolic syndrome, "sets the stage for a progression of lethal diseases" including "cancer, atherosclerosis, diabetes", and amplifies the risk of early cardiac death by more than eight-fold. Nonalcoholic fatty liver disease is associated with obesity and high blood sugar . The condition progesses to nonalcoholic steatohepatitis (a major risk factor for liver cancer or hepatocellular carcinoma) due to inflammation of excess fat leading to to liver fibrosis and cirrhosis that destroys liver functions . Non-alcoholic fatty liver disease leads to liver fat deposits that may become rancid and produce lipid peroxidation in the liver that can be combated by combining Cucumis melo extracts [Images] rich in SOD to convert free radicals producing rancid fat into hydrogen peroxide with Schisandra Chinensis extract that converts hydrogen peroxide into water by boosting glutathione levels . Non-alcoholic fatty liver disease is often associated with toxin-induced liver fibrosis, a condition that may be reversed in animal models by treatment with Reishi mushroom. Reishi mushrooms are anticancer, antioxidant, elevate nerve growth factor, and improve the life span of experimental mice . Non-alcoholic fatty liver disease may be treated with silymarin (Milk Thistle Extract) at typically 200 mg/day, which fights oxidative damage and inflammation leading to liver fibrosis . Milk Thistle Extract doses of up to 1000 mg/day are sometimes used. In addition, silymarin blocks the proliferation of colon, lung, cervical, prostate, and ovarian cancer cell lines . Silibinin from Milk Thistle Extract inhibits cell type transformation from epithelial to mesenchymal enabling tumor development and growth.
 Kirk Stokel (2012),
Novel Method to Effectively Combat Oxidative Liver Damage (from Non-alcoholic fatty liver disease), Life Extension Magazine January 2012.
 Emily Steiner (2013),
How Reishi Combats Aging, Life Extension Magazine, Feb 2013.
 Michael Campbell (2015),
The Silent Epidemic Of Liver Disease, Life Extension Magazine April 2015.
 Dietrich P, Hellerbrand C. (2014),
Nonalcoholic fatty liver disease, obesity and the metabolic syndrome,
Best Pract Res Clin Gastroenterol 2014 Aug;28(4):637-53.
 Paschos P, Paletas K (2009),
Non-alcoholic fatty liver disease and metabolic syndrome, Hippokratia 2009 2. Jan;13(1):9-19.
 Tolman KG, Dalpiaz AS. (2007),
Treatment of nonalcoholic fatty liver disease, Ther Clin Risk Manag 2007 Dec;3(6):1153-63.
Nonenzymatic Free Radical Scavengers [Links, Images, Papers, Patents, Books, LifeExtension], [35s] (c).
Nonenzymatic inhibition of glycation [Links, Images, Papers, Patents, Books, LifeExtension], [35s] (e).
Nootropics [Smart Drugs/Nootropics, reviewing the smart drugs, Links, Images, Video, Papers, Patents, Books, LibCong, LifeExtension, Amazon, Erowid/Nootropics; Index/Smart Drugs].
Norepinephrine [Links, Images, Video, Papers, Patents, Books, LifeExtension].
Norepinephrine, indomethacin [Images/indomethacin], naproxen [Images], and inflammation-suppressors inhibit cyclooxygenases COX1 and/or COX2, reducing risk for Parkinson's disease [Index] and other neurodegenerative diseases [Index]. Problems may exist for some dosage regimes. In particular, chronic use of aspirin interferring with COX-1 is often associated with a stomach ulcer.
N-tert-butyl Hydroxylamine (NtBHA) [Links/N-tert-butyl Hydroxylamine, Images, Video, Papers, Patents, Books, LifeExtension]. N-tert-butyl Hydroxylamine 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.
Nuclear Receptor Superfamily [Wikipedia/Nuclear Receptor, Links/nuclear recetor superfamily, Images, Video, Papers, Patents, Books, Amazon, LibCong, LifeExtension]. The nuclear receptor superfamily of transcription factors includes thyroid hormones, retinoic acid, and steroid hormones like the telomerase activator ecdysone. Nuclear receptor superfamily molecules [Images] are complexed with heat shock protein HSP90 [Wikipedia/HSP90, Links, Images, Video, Papers, Books, Amazon] before being transported into the cellular nucleus to bind to sites on gene promoters such as the hTERT promoter [Amazon, Images, Papers] that produces the hTERT catalytic component of telomerase, the telomeric DNA repair enzyme that can prevent cellular senescence by lengthening telomeres to promote youthful patterns of gene expression. However, recovery from cellular senescence is often pictured as irreversible after growth arrest, when the cell no longer responds to growth factors because the receptor-mediated endocytosis from the cell membrane no longer supports growth factor signaling when caveolin-1 is overexpressed and caveolae on the cell surface vanish, leaving only internal caveolae. Therapy has been devised for recovery from the senescent phenotype of the cell (Refs 9) with complete restoration of cell function based on reducing the expression of caveolin-1 with small molecule caveolin-1 inhibitors (such as cyclic AMP from forskolin or exercise) and stimulating the cell with growth factors such as EGF and PDGF or other telomerase activators. P16INK4A expression inhibiting recovery may be lowered with P16INK4A inhibitors to simplify restoration from the senescent state, as it is a ubiquitinated protein. See HSP90 activators [Links, Images, Papers, Patents, Books]. Note that HSP90 for transport to the nucleus may be obtained by exercising, which produces interleukin 6 leading to the generation of HSP90.
Alpha Lipoic Acid upregulates HSP expression
Note that alpha lipoic acid increases heat shock protein expression, including the expression of HSP90, which transports transcription factors into the cellular nucleus. See Index/Alpha Lipoic Acid.
Nuclear Reprogramming [Links, Images, Video, Papers, Patents, Books, LibCong, Amazon, LifeExtension]. Skin cells can be reprogrammed to provide pluripotent or totipotent stem cells with patient-bioidentical DNA. See (8) on stem cells. The key papers in nuclear reprogramming of skin cells for application as stem cells were seperately published by Dr. Shinya Yamanaka [Links, Images] of Kyoto University and UCSF in Cell [Papers, Links, Images] and James Thomson of the University of Wisconsin in Science [Papers, Links, Images]. Dr. Yamanaka showed that pluripotent stem cells can be generated [Links, Images, Papers, Patents, Books] from mouse embryonic fibroblasts and adult mouse tail tip fibroblasts by the retrovirus-mediated transfection of four transcription factors [Books], Oct3/4, Sox2, c-Myc, and Klf4. Embryonic stem cells may also start from youthful cellular DNA cloned by nuclear transfer technique from the cryopreserved cellular DNA of older specimens. The embryonic stem cells could then be differentiated to create younger bone marrow (or any other tissue that may be required) to be implanted in the body and find its way into the bones to ultimately rejuvenate the vascular endothelium and the immune system via rejuvenated bone marrow stem cells. See also Links/Dr. Michael West on Nuclear Reprogramming, human embryonic progenitor cells, Dr. West's company BioTime, Inc., Michael D. West, and induced Pluripotent Stem Cells (iPS cells) [Images, Papers, Patents, Books, Amazon, LifeExtension]. Also see Stem Cells, Stem Cell Techniques, and Stem Cell Transplants.
Nucleotide Supplements [Links, Images, Video, Papers, Patents, LifeExtension]. Nucleotide supplements have been formulated to lower cortisol levels and increase testosterone levels.
Nutraceuticals [Links/Nutraceuticals, Images, Video, Papers, Patents/Anti Aging Nutraceuticals, Books, LibCong, Amazon, LifeExtension]. See also Ben Best/Phytochemicals [Links, Images, Papers, Books, Amazon, LifeExtension], topic index, Micronutrients, Functional Foods, [41s], [44s]. See My-Health-Plan for a mouthwatering display of excellent nutraceutical suggestions. See Yuqing Dong, Sujay Guha, Xiaoping Sun, Min Cao, Xiaoxia Wang, and Sige Zou (2012), Nutraceutical Interventions for Promoting Healthy Aging in Invertebrate Models, Oxidative Medicine and Cellular Longevity, Volume 2012 (2012).
Nutritional Content of Foods [FitBit, Links, Images, Video, Papers, Books, LifeExtension, Amazon, LibCong].
Nutritional Genomics [Gene Families HUGO, Links/Nutritional Genomics, Images, Video, Papers, Books; Index/Pharmacogenomics]. See Young-Joon Surh, Zigang Dong, Enrique Cadenas, Lester Packer (2008), Dietary Modulation of Cell Signaling Pathways [Links, Images, Video, Papers, Patents, Books, LEF], (Google eBooks) CRC Press, Sep 26, 2008, 504 pages.
Nuts [RicciNuts, LifeExtension/Nuts, Links/The Food Value of Nuts, Images, Video, Papers, Books, Amazon; Books/Nuts in medicine], Linus Pauling Institute on Nuts, Links, [25e]. Note than Spanish peanuts are the best source for arginine. See arginine sources. Peanuts are also a fine source of gamma tocopherol. References
 Ros E. (2010), Health benefits of nut consumption, Nutrients 2010 Jul;2(7):652-82.
 Maguire LS, O’Sullivan SM, Galvin K, O’Connor TP, O’Brien NM (2004),
Fatty acid profile, tocopherol, squalene and phytosterol content of walnuts, almonds, peanuts, hazelnuts, and the macadamia nut, Int J Food Sci Nutr 2004 May;55(3):171-8.
 Rajaram S, Burke K, Connell B, Myint T, Sabaté J. (2001),
A monounsaturated fatty acid-rich pecan-enriched diet favorably alters the serum lipid profile of healthy men and women, J Nutr 2001 Sep;131(9):2275-9.
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