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
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.
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.
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).
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

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.

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