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Drugs that modulate aging: the promising yet difficult path ahead

Published:November 22, 2013DOI:https://doi.org/10.1016/j.trsl.2013.11.007
      Once a backwater in medical sciences, aging research has emerged and now threatens to take the forefront. This dramatic change of stature is driven from 3 major events. First and foremost, the world is rapidly getting old. Never before have we lived in a demographic environment like today, and the trends will continue such that 20% percent of the global population of 9 billion will be over the age of 60 by 2050. Given current trends of sharply increasing chronic disease incidence, economic disaster from the impending silver tsunami may be ahead. A second major driver on the rise is the dramatic progress that aging research has made using invertebrate models such as worms, flies, and yeast. Genetic approaches using these organisms have led to hundreds of aging genes and, perhaps surprisingly, strong evidence of evolutionary conservation among longevity pathways between disparate species, including mammals. Current studies suggest that this conservation may extend to humans. Finally, small molecules such as rapamycin and resveratrol have been identified that slow aging in model organisms, although only rapamycin to date impacts longevity in mice. The potential now exists to delay human aging, whether it is through known classes of small molecules or a plethora of emerging ones. But how can a drug that slows aging become approved and make it to market when aging is not defined as a disease. Here, we discuss the strategies to translate discoveries from aging research into drugs. Will aging research lead to novel therapies toward chronic disease, prevention of disease or be targeted directly at extending lifespan?

      Abbreviations:

      ADRB2 (β-adrenergic receptor), IGF (insulin-like growth factor), IIS (insulin/IGF signaling), LMNA (lamin A/C), NIA (National Institute on Aging), PKA (protein kinase A), TOR (target of rapamycin), TORC1 (target of rapamycin complex 1), TORC2 (target of rapamycin complex 2), SIR2 (silent information regulator 2), STACs (sirtuin activating compounds)
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