Richard Weindruch, Ph.D.
Room B72 Veterans Admin Hospital
2500 Overlook Terrace
Madison, WI 53705-2286
608-256-1901, ext. 11642
rhweindr@wisc.edu
Emphasis Group:
Human Nutrition
Principal Research Interest:
Influences of caloric intake on aging and oxidative stress
Research Summary:
Our group investigates the relationship between diet and aging
processes. The main focus is on caloric intake. It has been known
for more that than 50 years that caloric restriction (CR), without
malnutrition, will greatly extend the maximum life span of rats and
mice and decrease the incidence of cancer and other late-life diseases.
CR appears to retard the rate of aging in nearly all species tested
to date. Not only do rodents on CR live longer than normally fed controls,
but the biological changes that occur normally with aging occur at
a slower rate. The magnitude of CR's effects on longevity, diseases,
and age-sensitive biological parameters in rodents is unmatched by
other interventions.
Our research on CR is attempting to answer three questions:
What are the mechanisms that underlie the retardation of
aging and diseases by CR in rodents? Our current studies are testing
the hypothesis that CR retards aging by shifting mitochondrial energy
metabolism to a state promoting aging retardation. Collaborating with
Dr. Tomas Prolla, we are employing oligonucleotide microarrays to obtain
a global view of the transcriptional changes induced by aging and CR.
Can nutrients be discovered which mimic the actions of CR
in animals consuming a normal calorie intake? Our work has focused on
resveratrol, which is a leading candidate "CR mimetic".
Does CR retard aging and diseases disease processes in primates
in a fashion similar to its effects in rodents? Here, studies in non-human
primates (rhesus monkeys) are ongoing and we have recently demonstrated
aging retardation by CR in this model. Also, studies in humans on long-term
CR are ongoing.
Representative Publications:
Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison
DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R: Caloric restriction
delays disease onset and mortality in rhesus monkeys. Science (in press).
Anderson RM, Barger JL, Edwards MG, Braun KH, O’ Connor CE, Prolla TA, Weindruch
R: Dynamic regulation of PGC-1a localization and turnover implicates
mitochondrial adaptation in calorie restriction and the stress response.
Aging Cell 7:101-11, 2008.
Barger JL, Kayo T, Vann JM, Arias EB, Wang J, Hacker TA, Wang Y, Raederstorff
D, Morrow JD, Leeuwenburgh C, Allison DB, Saupe KW, Cartee GD, Weindruch
R, Prolla TA: A low dose of dietary resveratrol partially mimics caloric
restriction and retards aging parameters in mice. PloS ONE 3:e2264, 2008.
Colman RJ, Beasley TM, Allison DB, Weindruch R: Attenuation of sarcopenia by
dietary restriction in rhesus monkeys. J. Gerontol. A Biol. Sci. Med.
Sci. 63:556-9, 2008.
Higami Y, Barger JL, Page GP, Allison DB, Smith SR, Prolla TA, Weindruch R: Energy
restriction lowers the expression of genes linked to inflammation, the
cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose
tissue. J. Nutr. 136:343-52, 2006.
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