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.