X-Message-Number: 27996 Date: Fri, 26 May 2006 19:04:39 -0700 (PDT) From: Doug Skrecky <> Subject: modulating HO-1 & TNF-a may boost human longevity [ Caloric restriction can increase, have no effect or even decrease animal longevity depending on the species, and strain of the animal. Unfortunately, in aged animals, CR usually fails to improve longevity. CR is basically a young man's (or women's) game. For anti-aging techniques, aged humans will have to look elsewhere. The heat shock protein heme oxygenase (HO-1) is known to be effective in blocking atherosclerosis. Tumor necrosis factor alpha (TNF-a) is known to be a major driver in the mortality of centenarians. There exist a number of dietary and supplemental methods for increasing the protective HO-1, and lowering the damaging TNF-a. Hopefully before too many more years have passed, there will exist a set of well-researched, well-supported rejuvenation protocols which are more than mere wishful thinking, and more than skin deep.] Biogerontology. 2006 Apr 21; [Epub ahead of print] Effects of caloric restriction are species-specific. This article addresses two questions: (1) 'can caloric restriction (CR) extend the life spans of all species of experimental animals', and (2) 'is CR likely to slow the human aging process and/or extend the human life span?' The answer to the first question is clearly 'no', because CR decreases the life span of the housefly, Musca domestica, and fails to extend the life span of at least one mouse strain. The answer to the second question is unknown, because human CR has not yet been shown either to increase or curtail the human life span. However, recent efforts to develop insect models of CR have been unsuccessful and/or relatively uninformative, so any insights regarding the relationship between CR and human aging are more likely to arise from studies of established, mammalian models of CR. [Caloric intake per ses is not related to CVD mortality.] Exercise, body mass index, caloric intake, and cardiovascular mortality Abstract Background The association of physical inactivity and elevated body mass index (BMI) with cardiovascular disease (CVD) risk is well established. The relationship of dietary caloric intake and CVD risk is less certain. Methods The epidemiologic follow-up of the First National Health and Nutrition Examination Survey (1971-1992) was examined to determine the relationship of caloric intake, BMI, and physical activity to CVD mortality. Of 14,407 participants, 9790 subjects aged 25 to 74 years met inclusion criteria. The CVD mortality rate was the outcome. Results During the 17 years of follow-up, there were 3183 deaths, 1531 of which were due to CVD (9.11/1000 person-years). People with relatively less physical activity, lower caloric intake, and who were overweight (BMI 25 to 29.9 kg/m2) and obese (BMI >30 kg/m2) had a less favorable baseline CVD risk profile than did those who were more active and of normal weight and had greater caloric intake. Age- and race/ethnicity-adjusted CVD mortality rates were highest among those with the least physical activity and lowest caloric intake, and who were overweight or obese. Moreover, subjects of normal weight who exercised most were more likely to have high caloric intake and lower CVD mortality (5.9 vs 14.7 per 1000 person-years, p =0.01) than subjects who were obese and exercised least. In Cox regression analysis, controlling for relevant CVD risk factors, least physical activity was independently associated with increased CVD mortality (hazard RATIO=1.32, 95% confidence interval [CI]=1.13-1.53); and obesity was associated with increased CVD mortality (hazard RATIO=1.24, 95% CI=1.06-1.44). Although highest dietary caloric intake was associated with reduced CVD mortality (hazard RATIO=0.83, 95% CI=0.74-0.93), after adjusting for physical activity and BMI, there was no significant association of highest caloric intake with CVD mortality (hazard RATIO=0.91, 95% CI=0.81-1.01). Conclusions In this large general population sample, lower levels of physical activity and obesity were independently associated with decreased CVD survival. Moreover, when BMI, physical activity, and other relevant characteristics were taken into account, caloric intake was not related to CVD mortality. [The effect of resveratrol on mammalian longevity is unknown. In fish a large dose of this powerful TNF-a inhibitor dramatically increased maximum longevity. Resveratrol Longevity % increase Dosage Median Maximum 24 0 0 120 33 27 600 56 59 ] Curr Biol. 2006 Feb 7;16(3):296-300. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Resveratrol, a natural phytoalexin found in grapes and red wine, increases longevity in the short-lived invertebrates Caenorhabditis elegans and Drosophila and exerts a variety of biological effects in vertebrates, including protection from ischemia and neurotoxicity. Its effects on vertebrate lifespan were not yet known. The relatively long lifespan of mice, which live at least 2.5 years, is a hurdle for life-long pharmacological trials. Here, the authors used the short-lived seasonal fish Nothobranchius furzeri with a maximum recorded lifespan of 13 weeks in captivity. Short lifespan in this species is not the result of spontaneous or targeted genetic mutations, but a natural trait correlated with the necessity to breed in an ephemeral habitat and tied with accelerated development and expression of ageing biomarkers at a cellular level. Resveratrol was added to the food starting in early adulthood and caused a dose-dependent increase of median and maximum lifespan. In addition, resveratrol delays the age-dependent decay of locomotor activity and cognitive performances and reduces the expression of neurofibrillary degeneration in the brain. These results demonstrate that food supplementation with resveratrol prolongs lifespan and retards the expression of age-dependent traits in a short-lived vertebrate. Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=27996