MICRO » IT’S THE BEGINNING OF THE END OF THE BEGINNING « RICHARD A. MILLER Yet it doesn’t have to be this way. Broad-acting preventive medicines could dramatically increase the period of life spent in good health – our healthspan. This ray of hope reflects progress in the science of aging, or geroscience. We now possess reams of data about how healthy lifestyles can lower risks of age-related diseases. Geroscientists have also discovered that altering certain genes can significantly slow time’s toll in animals to enhance longevity and health in later life. Interventions that slow the rate of aging are now a realistic prospect. They would represent a “superefficient” way to attack the diseases of aging, says Goldman, because they would delay all of the diseases at once to extend the period of healthy life. His 2013 study showed that preventive interventions that only modestly delay aging could achieve much greater reductions in disability and per capita medical costs than the reactive approach. For example, according to research by Goldman, a drug that increased life expectancy at age 51 by only 2.2 years in 2030 could, by 2060, boost the number of healthy, non-disabled older Americans by more than 11 million. To be sure, anti-aging interventions would likely increase the number of elderly people eligible for government entitlement programs, increasing the programs’ total costs. But Goldman’s study showed these costs could be readily offset by slightly raising eligibility ages for the programs to reflect the fact that older people would be healthier and living longer. HOW TO DELAY AGING Laboratory findings that suggest aging can be slowed date to 1935, when scientists discovered that putting rats on very-low-calorie diets extends their lifespans by a third or more. Later studies showed that such calorie restriction, or CR, can delay aging in many species. Importantly, it also makes animals healthier in their extended later years. For decades, CR remained little more than a lab curiosity. Its dietary regimen was demanding and there was no definite proof it worked in humans; its mechanism of action was too obscure to suggest drugs that would mimic its benefits. This situation began to change in the 1990s, however, when scientists discovered gene mutations in worms, flies and mice that extend healthy lifespan much as CR does. Analyzing what these mutations do within cells has suggested that there’s a latent, anti-aging capacity in the body engendered by networks of interacting genes. These networks can be switched on by CR and by mutations in specific genes, most notably those that govern growth early in life. Probing the networks’ molecular constituents has suggested that certain drugs might tap them to slow aging. In 2003, the U.S. National Institute on Aging launched a program to test such drugs’ effects on lifespan in mice. Six years later, it yielded an unprecedented success: rapamycin, a medicine used to prevent rejection of transplanted organs, robustly extended life expectancy in elderly mice by about a third. Subsequent studies have shown that the drug also reduces cancer, neurodegeneration and other ills while improving liver, heart, kidney and muscle function in mice. Rapamycin’s side effects, such as increased blood sugar, may rule it out as a possible anti-aging drug. But other candidates include acarbose, a drug for lowering blood sugar in diabetics, and another diabetes drug, Metformin, which mimics key effects of CR while increasing both healthspan and lifespan in mice. Rigorously validated anti-aging drugs would still take many years to develop. Among other hurdles, scientists must find “biomarkers” to measure the rate of aging so that candidate drugs can be tested in relatively short clinical trials. Still, “it’s the beginning of the end of the beginning,” in humanity’s long quest to delay aging, says Richard A. Miller, professor of pathology at the University of Michigan. And while the modestly slowed aging that geroscientists now feel is achievable wouldn’t repeal the Murphy’s law of aging, it would profoundly reduce its penalties. 38 • Allianz
HOLDING BACK Geroscientists are discovering ways to slow time’s toll to enhance longevity and healthspan Allianz • 39