* Metformin increases lifespan in Mice by 5.83% when started in middle age mice
* Reveratrol improves health but is not showing a significant increase in lifespan
* Rapamycin suppresses cancer tumors, Rapamycin life extension is because the mice do not die early from cancer
1. Long-term treatment with the type 2 diabetes drug metformin improves health and longevity of male mice when started at middle age, reports an international team of scientists led by researchers at the National Institute on Aging (NIA), part of the National Institutes Health. The study, which tested two doses of the drug in the male mice, found the higher dose to be toxic in the animals. Scientists emphasized that considerably more research is needed before the implications of metformin for healthy aging are known for humans.
The study, headed by Rafael de Cabo, Ph.D., of the NIA’s Intramural Research Program, was published in the July 30, 2013 issue of Nature Communications.
In this study, researchers found male mice on a 0.1 percent metformin treatment had a 5.83 percent increase in lifespan compared to control group mice on a standard diet with no metformin. The 1 percent metformin treatment had the opposite effect. These mice had a 14.4 percent shorter lifespan compared to the control group, likely due to kidney failure. The lower metformin dose did not seem to cause any negative effect on the renal system.
A battery of tests performed with male mice taking 0.1 percent, 1 percent, or no metformin starting at middle age, revealed a clear health benefit of the 0.1 percent treatment.
These mice had improved general fitness and weighed less than the control group mice, despite consuming more calories. Metformin increased their use of fat for energy. Mice on metformin tended to preserve body weight with age, a characteristic associated with increased survival in other studies. They had a lower incidence of cataracts, a common health problem in the strain of mouse. Not surprisingly, metformin prevented the onset of metabolic syndrome. It had similar effects as calorie restriction on genes in the liver and muscles, which induced longevity-associated activity in the mice. Metformin also appeared to have some antioxidant effects in the mice.
A number of compounds are being tested for their possible applications to improving health with aging. A previous study by de Cabo and colleagues found that resveratrol, present in foods like grapes and nuts, improved a number of health measures in mice, but perhaps not their longevity.
2. Journal of Clinical Investigation - Rapamycin extends murine lifespan but has limited effects on aging
Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest for novel and broadly effective treatments against age-related diseases. The recent report of lifespan extension in mice treated with the FDA-approved mTOR inhibitor rapamycin represented the first demonstration of pharmacological extension of maximal lifespan in mammals. Longevity effects of rapamycin may, however, be due to rapamycin’s effects on specific life-limiting pathologies, such as cancers, and it remains unclear if this compound actually slows the rate of aging in mammals. Here, we present results from a comprehensive, large-scale assessment of a wide range of structural and functional aging phenotypes, which we performed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin did extend lifespan, it ameliorated few studied aging phenotypes. A subset of aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar effects on many of these traits in young animals, indicating that these effects were not due to a modulation of aging, but rather related to aging-independent drug effects. Therefore, our data largely dissociate rapamycin’s longevity effects from effects on aging itself.
Rapamycin was previously reported to extend lifespan, even if treatment is initiated late in life. To determine whether age of treatment onset is an important variable affecting the possible healthspan effects of the drug, we included 3 different cohorts in our study, in which rapamycin or vehicle control treatment commenced in young adulthood (i.e., at 4 months), in midlife (i.e., at 13 months) or late in life (i.e., at 20–22 months). Animals were treated with rapamycin for 1 year before analyses commenced (i.e., analysis at 16, 25, or 32–34 months, respectively), unless otherwise stated.
Rapamycin-induced lifespan extension is known to occur in mice of both genders (with larger effect sizes in females in a genetically heterogeneous stock of mice). We therefore focused our study on one sex. We chose to analyze male mice because a proper analysis of females would have required taking into account phenotypic variation associated with the estrus cycle.
In the recent study by Miller et al. (using genetically heterogeneous mice; ref. 10), 95.6% of control animals and 88.6% of rapamycin-treated animals had neoplastic disease as their likely cause of death. Both vehicle- and rapamycin-treated animals eventually died of cancers, but controls did so at younger ages.
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