X-Message-Number: 22441 From: "michaelprice" <> References: <> Subject: Re: sirtuin activating compounds & life extension Date: Sun, 31 Aug 2003 05:55:12 +0100 Thanks Doug for posting the article on sirtuins. The implication of Drs Guarente, Sinclair, and Howitz's work taken all together is that resveratrol acts though the sirtuins (SIR2 proteins). NAD (the coenzyme form of vitamin B3) is a substrate for sirtuins, which consequently up-regulates sirtuin activity. Ergo you might get the same life-extension effect from inositol hexanicotinate (a dietary precursor of NAD & a form of vitamin B3) as resveratrol, namely a life-extension comparable with calorie restriction (i.e. 30-50% LE). Niacinamide (another form vitamin B3), like resveratrol, has extended the lifespan of fruitflies, but not yet been tested for LS effects on a mammal. NAD is also a substrate for PARP which repairs DNA damage. This is believed to be why consumption of vitamin B3, in large doses (see ref's below) reduces carcinogensis by over 40%. Vitamin B3 may turn out to be the most potent of all the B-vitamins to slow down aging. The safest form to take vitamin B3 as is inositol hexanicotinate. There is an on-going discussion of these topics on the newsgroup sci.life-extension. [27a] Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Lin SJ, Defossez PA, Guarente L in Science 2000 Sep 22;289(5487):2126-2128 PMID: 11000115 [27b] Manipulation of a Nuclear NAD+ Salvage Pathway Delays Aging without Altering Steady-state NAD+ Levels. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H, Lin SS, Manchester JK, Gordon JI, Sinclair DA in J Biol Chem 2002 May 24;277(21):18881-90. PMID: 11884393 [27c] Oral Niacin Prevents Photocarcinogenesis and Photoimmunosuppression in mice. Gensler HL, Williams T, Huang AC, Jacobson EL in Nutrition and Cancer 34(1) (1999), pg 36-41. PMID: 10453439 The relationship between dietary intake of niacin and tissue NAD elevation is detailed in the main body of the article. The UV-irradiated mice on a diet with 0.003%, 0.1%, 0.5% & 1.0% niacin had a 0.72, 0.60, 0.48 & 0.40 tumours/mouse, respectively; a 44% reduction. The authors hypothesize that the cancer-protective effect is mediated by NAD-induced PARP activity. [27d] Mapping the role of NAD metabolism in prevention and treatment of carcinogenesis. Jacobson EL, Shieh WM, Huang AC in Mol Cell Biochem 1999 Mar;193(1-2):69-74 PMID: 10331640 NAD is elevated by niacin in many human tissues. [27e] Evaluating the role of niacin in human carcinogenesis. Jacobson EL, Dame AJ, Pyrek JS, Jacobson MK. Biochimie 1995;77(5):394-8 PMID: 8527495 [27f] Protective effect of nicotinamide on bracken fern induced carcinogenicity in rats. Pamukcu AM, Milli U, Bryan GT in Nutr Cancer 1981;3(2):86-93 PMID: 6213941 0.5% nicotinamide in diet cut the induced cancer rate by 40% [27g] Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W in J Am Coll Cardiol 1986 Dec;8(6):1245-55 PMID: 3782631 "With a mean follow-up of 15 years, nearly 9 years after termination of the trial, mortality from all causes in each of the drug groups, except for niacin, was similar to that in the placebo group. Mortality in the niacin group was 11% lower than in the placebo group (52.0 versus 58.2%; p = 0.0004). " [27h] Pharmacological intakes of niacin increase bone marrow poly(ADP-ribose) and the latency of ethylnitrosourea-induced carcinogenesis in rats. Boyonoski AC, Spronck JC, Jacobs RM, Shah GM, Poirier GG, Kirkland JB in J Nutr 2002 Jan;132(1):115-20 PMID: 11773517 "This study was designed to test the effects of supplementing an already high quality diet with pharmacologic levels of niacin. [...] Supplementation with NA or Nam at 4.0 g/kg diet (combined analysis) increased the latency of the ENU-induced morbidity curve, relative to niacin-adequate controls. Morbidity could be attributed in almost all cases to some form of neoplasm, with leukemias the predominant form. In short-term studies, supplementation with either NA or Nam caused dramatic increases in bone marrow NAD(+) (1- to 1.5-fold), basal poly(ADP-ribose) (3- to 5-fold) and ENU-induced poly(ADP-ribose) levels (1.5-fold). These data show that supplementation of a niacin-adequate, high quality diet with pharmacologic levels of nicotinic acid or nicotinamide increases NAD(+) and poly(ADP-ribose) levels in bone marrow and may be protective against DNA damage." Cheers, Michael C Price http://mcp.longevity-report.com http://www.hedweb.com/manworld.htm Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=22441