Jan Vijg1 and Steven N. Austad2 1Department of Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA 2Protective Life Endowed Chair in Healthy Aging Research, Department of Biology, The University of Alabama at Birmingham, Birmingham, Alabama 35233, USA Correspondence: jan.vijgeinsteinmed.edu; austaduab.edu

Multiple observations that organismal life span can be extended by nutritional, genetic, or pharmacological intervention has raised the prospect of transforming medicine with the goal of slowing, stopping, or even reversing age-associated disease and maintaining or restoring health and resilience in the increasing numbers of elderly across the world. The potential for such an enterprise is supported in theory by plant and animal models of negligible senescence, most notably the small, freshwater organism Hydra spp. The existence of some very long-lived species, including bowhead whale, Greenland shark, and giant tortoises, suggests that increased healthy life spans in humans, significantly higher than the current known maximum life span of about 120 years, may be possible. Here we discuss the biological restraints on human life extension based on the evolutionary basis of aging and our current genetic and molecular insights into the processes responsible for age-related loss of function and increased disease risk.