Index to Anti-Aging Medicine
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N
N-Acetyl Cysteine (NAC) [Telomerase Activators/NAC, Links/N-Acetyl Cysteine, Images, Video, Papers, Patents, Books, LifeExtension, Ben Best/NAC]. See NAC in heavy-metal & mercury chelation, plus chelation of arsenic, cadmium, and lead, as LEF product, (1), [31s]. NAC is a highly bioavailable form of L-Cysteine, and a powerful antioxidant taken at 600 mg/day to 1800 mg/day that replenishes glutathione (GSH), in addition to being a premier scavenger of heavy metal ions. NAC induces apoptosis in many kinds of cancer cells, and has been useful in reducing corectal polyps [Images] at 600 mg/day to 1200 mg/day. Furthermore, NAC controls obesity-associated insulin resistance arising from the production of inflammatory signaling molecules in fat cells. NAC is also effective against bird flu, inhibiting replication of H5N1 virus and associated expression of pro-inflammatory cytokines, and shows anti-viral effect against influenza and its associated "cell boiling" effects, especially when given with green tea and 1600 mg of arginine. NAC is not available from the diet, and must be taken as a supplement, like acetyl L-Carnitine, a more bioavailable form of L-carnitine synthesized by scientists. It influences gene expression in the reduction of inflammation associated with NF-kappa-B and TNF-alpha, and is effective against acetaminophen (Tylenol) toxicity and acute liver failure, influenza ("3/4 of all flu-related deaths occur in the elderly"), chronic lung diseases ("including emphysema and chronic bronchitis"), cancers, insulin resistance, and gastritis due to H. Pylori ("linked to gastric cancer, the 2nd most frequent cause of cancer death worldwide"). "NAC blocks cancer development at virtually every step in the process, and through multiple mechanisms, making it an important cancer chemopreventive agent." NAC reduces the carcinogenicity of tobacco smoke. - See The Overlooked Compound that Saves Lives: N-Acetyl Cysteine by Julius Goepp, MD, Life Extension Magazine, May 2010. Note that NAC was used early on as a mucous thinning agent (mucolytic) taken in a mucolytic inhalant for treating diseases like cystic fibrosis featuring thick mucous. Note that cystic fibrosis may be cured using gene therapy by application of Zinc Finger Nuclease technology. NAC is used by vigorously exercising men to protect cells against oxidative stress and maintain high glutathione, defending brain tissue and levels of vital lymphocytes. NAC also helps to prevent stomach cancer induced by Helicobacter pylori infections leading to gastric cancerogenesis. See Deflora S, Izzotti A, D'Agostini F, Balansky RM (2001), Mechanisms of N-acetyl cysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points, Carcinogenesis, 2001, July;22(7):999-1013. Kerksick C, Willough D (2005), The antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stress, Journal of the International Society of Sports Nutrition 2005;2:38-44. Quadrilatero J, Hoffman-Goetz L (2004), N-acetyl-L-cysteine prevents exercise-induced intestinal lymphocyte apoptosis by maintaining intracellular glutathione levels and reducing mitochondrial membrane depolarization, Biochemistry and Biophysics Research Communications 2004 July 2;319(3):894-901. Perhaps NAC can be used to improve the effectiveness of telomerase activators by blocking the action of telomerase inhibitors. [Longecity Forum Note]. "Chronic exposure to NAC can delay senescence of diseased endothelial cells via hTERT activation and transient telomere stabilization, unless oxidative stress-associated cell damage has become irreversible." - after Guillaume Voghela, Nathalie Thorin-Trescasesa, Nada Farhata, Aida M. Mamarbachia, et al (2008), Chronic treatment with N-acetyl-cystein delays cellular senescence in endothelial cells isolated from a subgroup of atherosclerotic patients, Mechanisms of Ageing and Development, Volume 129, Issue 5, May 2008, Pages 261–270. See also Macip S, Igarashi M, Fang L, Chen A, Pan ZQ, Lee SW, Aaronson SA (2002), Inhibition of p21-mediated ROS accumulation can rescue p21-induced senescence, [PubMed Abstract], EMBO Journal 2002 May 1;21(9):2180-8. In this paper NAC was used to abolish p21-induced senescence.
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

NAD+ + 2e- + H+ <---> NADH .

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].

Oral Phytoceramides
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
(1) Tilting the head back,
(2) Pressing the tongue to the roof of the mouth,
(3) Bringing the neck down and contracting while pressing the tongue to the roof of the mouth.
Another neck-muscle, neck-firming exercise that is useful is to
(1) Throw the head back over one shoulder.
(2) Move the jaw forwards in a way that strains the neck muscle for several reps.
(3) Repeat for the other shoulder, to exercise both sides.

Neck-Flattening Isometrics
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
(1) acetyl hexapeptide-3
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams],
(2) hyaluronic acid [Index]
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams],
(3) retinol
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams],
(4) N-acetyl glucosamine
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams],
(5) niacinamide [Index]
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams],
(6) CoQ10 [Index]
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams],
(7) concentrated tea extracts [Index]
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams],
(8) alpha-lipoic acid [Index]
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams], and
(9) DMAE [Index]
__[Links, Images, Video, Papers, Patents, Books, LEF; supplements, skin creams,
__DMAE instant anti-aging face lift (Images, Video, Papers, Patents, Books, LEF)].
can help protect the skin of the neck and reduce the signs of aging." - Gary Goldfaden, MD (2012), Topical Nutrients to Revitalize the Aging Neck, Life Extension Magazine, Nov 2007 [Refs11a]. Note that colostrum skin creams contain TGF-beta, which reconstructs collagen and elastin in the extracelluar matrix. Colostrum skin creams also contain growth factors that lengthen telomeres in dermal fibroblasts. See also skin creams improving the expression of integrins [Images, Papers, Patents, Books, LifeExtension], such as Syn-Tacks and Hexapeptide-10. Note also that genistein [Images], a telomerase inhibitor, improves the expression of elastin. Therefore soy-based products such as soy milk and soy skin creams or genistein skin creams may be useful in neck restoration. Anti-collagenase, anti-elastase extracts such as white tea may also be quite useful, as may anti-elastase phytoceramides. Ceramide expression may be boosted by lactic acid from pumping up with weights. Furthermore, phosphatidylcholine (lecithin), which improves the bioavailability of wrinkle cures such as quercetin and resveratrol, is underexpressed in old necks and may be supplemented.

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.
Sodium Butyrate improves the expression of hTR by increasing the expression of transcription factor Sp1. 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:
(1) Hexapeptide-10
____[Links, Images, Video, Papers, Patents, Books; supplements, skin creams].
____Restores the dermo-epidermal junction connectivity, reviving elasticity and firmness.
____Stimulates expression of laminin-5, alpha6-integrin, and hemidesmosomes
____to restore dermal-epidermal connectivity.
____See Serilesine [Links, Images, Video, Papers, Patents, Books; skin cream;
____Tech Data, Tech Data2;
____Lipotec: The Scientific Response to Different Types of Wrinkles].
____Available from Lotion Crafter: Serilesine Solution GC (0.5% hexapeptide-10) $9.35.
____See SKN complex FACE LIFT with serilesine, $59.00.
____Hexapeptide-10 is in LEF's Cosmesis Tightening and Firming Night Cream $39.00.
____Included in Dermedicine's Tightening Neck Therapy Cream $70.00.
____Included in Calori Neck Cessity Cream 30ml $34.50.
____Included in CSI Rejuvenating Neck Cream - 1 oz $16.00.
(2) Acetyl-dipeptide-13 diphenylglycine
____[Links, Images, Video, Papers, Patents, Books; supplements, skin creams].
____Restores skin tightness, halting elastin breakdown and stimulating
____collagen type I synthesis.
____Included in LEF's Cosmesis Tightening and Firming Night Cream $39.00.
____Included in Dermedicine's Tightening Neck Therapy Cream $70.00.
____Included in Calori Neck Cessity Cream 30ml $34.50.
____Included in CSI Rejuvenating Neck Cream - 1 oz $16.00.
(3) Goji berries
____[Index, Links, Images, Video, Papers, Patents, Books; supplements, skin creams].
____This superior antioxidant protects skin from free radicals.
(4) Indian gooseberry
____[Links, Images, Video, Papers, Patents, Books; supplements, skin creams].
____Defends skin elasticity against UV damage.
(5) Hyaluronic acid
____[Index, Links, Images, Video, Papers, Patents, Books; supplements, skin creams].
____Boosts skin tone and hydration.

Senescent Cell Recovery Creams
Tocotrienol-rich fraction (173) has been proven useful for restoring senescent dermal fibroblasts with telomerase activation. I am interested in experiments with rice bran oil, which contains a substantial quantity of tocotrienol fraction, and with concentrated preparations of tocotrienol fraction sold as tocotrienol-based vitamin E. Skin rejuvenation creams which contain small molecule caveolin-1 inhibitors such as folic acid and glycyrrhiza in combination with growth factors such as EGF and PDGF may be able to restore senescent dermal fibroblasts to their youthful state with very substantial telomere length gains from hyperactivation of the ERK kinase cascade and consequent activation of Elk, which is observed when caveolin-1 (gene CAV1) downregulation is strong enough. Adding an amphipathic alcohol such as isopropyl rubbing alcohol improves skin penetration, as does introducing milk lipid liposomes prepared with an ultrasonic cleaner. Extra EGF might be added to colostrum with folic acid or glycyrrhiza for better results.
Necrosis [Wikipedia, Links, Images, Video, Papers, Patents, Books, Amazon, LibCong]. Necrosis is cell death or cell destruction with cell lysis [Images, Video] of cell contents into neighboring tissues. On the other hand, apoptosis [Links, Video, Images] cross-links cell contents before cell membrane dissolution [Images].
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:
(1) Rosemary [Images, Papers, Patents, Books, LifeExtension],
(2) Rosemary extracts [Images, Papers, Patents, Books, LifeExtension],
(3) Acetyl L-carnitine [Images, Papers, Patents, Books, LifeExtension],
(4) Acetyl L-carnitine arginate [Images, Papers, Patents, Books, LifeExtension],
(5) Carnosic acid [Images, Papers, Patents, Books, LifeExtension],
(6) Huperzine A [Images, Papers, Patents, Books, LifeExtension], and
(7) Pyrroloquinoline quinone (PQQ) [Images, Papers, Patents, Books, LifeExtension].
(8) Reishi Mushroom [Images, Papers, Patents, Books, LifeExtension, Ref1, Ref2].
Pyrroloquinoline quinone (PQQ) "stimulates production and release of nerve growth factor in cells that support neurons in the brain". (Perry Marcone, Generate Fresh Mitochondria with PQQ, Life Extension Magazine, February, 2011.) NGF is also elevated by the toxin okadaic acid [Images, Patents], which is found in melanoma cells and diarrheal shellfish poisoning, and which coincidentally promotes hTERT transcription to activate telomerase. However, okadaic acid is probably not to be used. See supplements elevating Nerve Growth Factor levels. NGF stimulates neurite growth, helping to combat dementia and old age cognitive decline. Note that NGF levels were significantly higher for experimental subjects in love, and that levels stayed high for a year after falling in love. In addition, Nerve Growth Factor stimulates the transcription of Id-1 helix-loop-helix transcription factor which acts on the hTERT promoter to enhance hTERT mRNA levels, ultimately producing more of the catalytic component of telomerase. Id-1 helix-loop-helix protein, a telomerase activator, also inhibits the expression of tumor suppressor protein p16INK4a (Zheng et al. 2004, Ohani et al. 2001), which can induce senescence after accumulating to high levels. High levels of p16INK4A make recovery from replicative senescence difficult.
Nervous breakdown [Links, Papers, Patents, Books, LifeExtension; Links/stress-induced nervous breakdowns, Links/drug-induced nervous breakdowns; Links/psychosocial stressors], [98]. 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 [95]. 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.
References
[1] 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].
[2] 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.
[3] 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.
References
[1] 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
Neuronal Regeneration after Stroke
___[Images, Video, Papers, Patents, Books, LEF, Amazon],
Neuronal Regeneration after Spinal Cord Injury
___[Images, Video, Papers, Patents, Books, LEF, Amazon],
Neuronal Regeneration and Alzheimer's Disease
___[Images, Video, Papers, Patents, Books, LEF, Amazon],
Neuronal Regeneration and Parkinson's Disease
___[Images, Video, Papers, Patents, Books, LEF, Amazon], and
Remyelination
___[Index, Images, Video, Papers, Patents, Books, LEF, Amazon].
Note that Pyrroloquinoline quinone (PQQ) stimulates mitochondrial biogenesis and nerve growth factor expression, promoting healing and regeneration of nerve cells in the wake of neural injuries from Alzheimer's, Parkinson's, and other sources. See Ashwaganda and Acetyl L-Carnitine, which can greatly increase Nerve Growth Factor expression.
Neuropathy (Encyclopedia).
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, [79], (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:
Cell Transformation Genes [Papers, Books]: IAP1 [Papers, Patents, Books],
c-Myc [Papers, Patents, Books].
Cell Survival Genes [Papers, Books]: Bcl-2 [Papers, Patents, Books],
c-IAP [Papers, Patents, Books],
TRAF [Papers, Patents, Books],
SOD [Papers, Patents, Books],
gamma-GC8 [Papers, Patents, Books].
Cell Proliferation Genes [Papers, Books]: Cyclin D1 [Papers, Patents, Books],
CDK2 kinase [Papers, Patents, Books],
GADD45 [Papers, Patents, Books],
p21 [Papers, Patents, Books].
Invasion Genes [Papers, Books]: MMP-9 [Papers, Patents, Books],
uPA [Papers, Patents, Books],
IL-8 [Papers, Patents, Books].
Angiogenesis Genes: [Papers, Books]: VEGF [Papers, Patents, Books],
MCP-1 [Papers, Patents, Books],
CD34 [Papers, Patents, Books].
Metastasis Genes [Papers, Books]: ICAM-1 [Papers, Patents, Books],
VCAM-1 [Papers, Patents, Books],
ELAM-1 [Papers, Patents, Books].
Inflammation Genes [Papers, Books]: TNF [Papers, Patents, Books],
IL-1 [Papers, Patents, Books],
Cox-2 [Papers, Patents, Books],
iNOS [Papers, Patents, Books],
CXCR4 [Papers, Patents, Books].
- after (Ravindran J, Aggarwal BB, 2010).
"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:
Black tea extract [Images, LifeExtension, Remarks].
Grape seed extract [Images, LifeExtension, Remarks],
Pterostilbene [Images, LifeExtension, Remarks],
Quercetin [Images, LifeExtension, Remarks], and
Resveratrol [Images, LifeExtension, Remarks].
(Julius Goepp, MD, Activate Your Longevity Genes via Caloric Restriction, Life Extension Magazine, Feb. 2010).

NF-kB inhibitors derived from spices [Ref] include:
Anethole [from Fennel Seed or Anise],
Carnosol [from Rosemary],
Caryophyllene [from Black Pepper],
Cinnamaldehyde [from Cinnamon bark],
Curcumin [Index, from Turmeric],
Humulene [from essential oils of hops],
Perillyl alcohol [from oils of lavender, peppermint, cherries, sage, and lemongrass],
Quercetin [Index, from onions and apples],
Sage,
Sulforaphane [Index, from broccoli sprouts], and
Ursolic acid [Index, from apple skins].

NF-kB inhibitors useful for anticancer applications also include:
Aged Garlic Extracts [Images, LifeExtension],
____diallyl sulfide [Images, LifeExtension] (causes significant muscle hypertrophy),
____diallyl disulfide [Images, LifeExtension], (also an HDAC Inhibitor),
____diallyl trisulfide [Images, LifeExtension] (check),
____thiacremonone [Images, LifeExtension],
Antioxidants preventing NF-kB transcription factor entry into the nucleus:
___Carotinoids [Images, LifeExtension],
___Genistein (a soy isoflavone) [Images, LifeExtension],
___Green tea catechins [Images, LifeExtension],
___Flavonoids (antioxidant) [Images, LifeExtension],
___Lycopene [Images, LifeExtension],
___Luteolin [Images, LifeExtension]
______(from celery, camomile tea, parsely, sage, thyme, peppermint, and basil),
___Melatonin [Images, LifeExtension; Remarks],
___Omega-3 fatty acids [Images, LifeExtension],
___Polyphenols (Antioxidant) [Images, LifeExtension],
___PycnogenolTM [Images, LifeExtension],
___Selenium [Images, LifeExtension],
___Thiol Antioxidants [Images, LifeExtension],
______Glutathione [Images, LifeExtension],
______Thioredoxin [Images, LifeExtension],
______Lipoic Acid [Images, LifeExtension],
___Vitamin C [Images, LifeExtension],
___Vitamin E [Images, LifeExtension],
___Vitamin K2 [Check: Links, Papers, Images, LifeExtension],
___Zinc [Images, LifeExtension].
Ashwagandha (Withania Somnifera) [Images, LifeExtension],
___Withanolide sulfoxide from ashwagandha roots inhibits NF-kB and metastasis.
Black Pepper antioxidants [Images, LifeExtension],
Coffee diterpenes [Images, LifeExtension],
___Cafestol [Images, LifeExtension],
___Kahweol [Images, LifeExtension],
Curcumin [Images, LifeExtension] from the spice turmeric [Images, LifeExtension],
Ginger [Images, LifeExtension],
___Gingerol [Images, LifeExtension],
___Zerumbone [Images, LifeExtension],
Lycopene [Images, LifeExtension],
Milk Thistle (Silymarin, Silibinin) [Images, LifeExtension],
Pomegranate [Images, LifeExtension], and
Vitamin D [Images, LifeExtension].
NFkB is the inflammatory factor underlying most cancers [1], [2]. Note that some NF-kB inhibitors are also telomerase inhibitors and most appear on lists of anticancer nutraceuticals. NF-kB itself is a telomerase activator and is often described as a tumor promoter, as is TNF-alpha. Garlic, curcumin (from turmeric), green tea, milk thistle (silymarin, silibinin), and vitamin D are NF-kB inhibitors, telomerase inhibitors for cancer cells, and on our anticancer nutraceuticals list. Milk thistle extract, curcumin (turmeric root extract), and green tea behave like a telomerase activators when applied to normal, non-cancerous fibroblasts, according to Product B literature.
[1] David Hoffnung (2011),
The Inflammatory Factor Underlying Most Cancers, Life Extension Magazine, Nov 2011.
[2] 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.
[3] 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
[1] 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.
[2] 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.
[3] 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], [112]. 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:
(1) Arginine (3-10 grams) promotes nitric oxide.
(2) Arginine (3-10 grams) with whey protein and bodybuilding exercise promotes NO.
(3) L-Arginine (3-10 grams) plus L-Citrulline (3-10 grams) promotes NO.
(4) Caloric restriction induces eNOS production, promoting NO levels and
___mitochondrial biogenesis [Ref].
(5) Cocoa contains NO-stimulating arginine (100 mg/tablespoon).
(6) Chocolate contains NO-stimulating arginine, 1,286 mg per oz of chocolate.
(7) Exercise promotes nitric oxide production [Ref].
(8) Horny goat weed boosts NO levels by inhibiting NO decomposition.
(9) Pomegranate increases the synthesis of NO.
(10) PycnogenolTM promotes nitric oxide by enhancing nitric oxide synthase function.
(11) Resveratrol [Books] promotes higher NO levels.
(12) Supplements promoting NO: Life Extension's Endothelial Defense.
(13) Histidine forms histamine, which enhances Nitric Oxide expression by promoting
____the activity of nitric-oxide synthase (NOS), which synthesizes NO from arginine.
____A practical dose to boost NO is 1-2 grams of L-Histidine or
____Histidine Alpha-Ketoglutarate.
(14) Extra virgin olive oil (2 tablespoons/day), due to high polyphenol content.
Gamma tocopherol may be taken along with nitric oxide boosting supplements to reduce lipid peroxidation from nitric oxide. Jeanne Calment took about 5 pounds of chocolate per week (yielding 14.696 grams/day of arginine), and drank red wines containing resveratrol. Thus Jean Calment's extremely long lifetime of 122.45 years may have been due to telomerase activation from nitric oxide activation, preventing the cellular senescence of endothelial cells lining veins and arteries, and cutting off atheroscelerosis causing heart attacks and strokes, two of the most common causes of death in aging adults.
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 [1]. 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.
References
[1] 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 [3]. 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 [3]. 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 [1]. 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 [2]. 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 [3]. 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 [3]. Silibinin from Milk Thistle Extract inhibits cell type transformation from epithelial to mesenchymal enabling tumor development and growth.
References
[1] Kirk Stokel (2012),
Novel Method to Effectively Combat Oxidative Liver Damage (from Non-alcoholic fatty liver disease), Life Extension Magazine January 2012.
[2] Emily Steiner (2013),
How Reishi Combats Aging, Life Extension Magazine, Feb 2013.
[3] Michael Campbell (2015),
The Silent Epidemic Of Liver Disease, Life Extension Magazine April 2015.
[4] 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.
[5] Paschos P, Paletas K (2009),
Non-alcoholic fatty liver disease and metabolic syndrome, Hippokratia 2009 2. Jan;13(1):9-19.
[6] 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
[1] Ros E. (2010), Health benefits of nut consumption, Nutrients 2010 Jul;2(7):652-82.
[2] 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.
[3] 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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