Balancing the promise and risks of geroscience

The geroscience hypothesis – that by intervening on the basic biological mechanisms of aging we could simultaneously reduce the risks of many chronic diseases and dramatically improve healthspan – has garnered substantial traction and enthusiasm in the past decade. And indeed, if successful, there is enormous potential to reduce the burden of disease in human populations. However, there are also reasons to be cautious, and these have received substantially less attention. Aging differs from traditional disease targets in a number of ways: (1) it is hard to define; (2) the biology of aging has likely been carefully calibrated by natural selection to balance multiple trade-offs, which are still poorly understood; (3) interventions may need to start decades before all benefits and harms are apparent; and (4) it is hard to disambiguate the cumulative effects of poor lifestyles from aging, but interventions for the two could be different. Together, these challenges, and the complex and interdependent nature of the underlying biology, mean that interventions that result in improvements in function or for certain biomarkers of aging and appear beneficial in the short term might still have a substantial chance of being harmful in the long-term, particularly if the interventions are acting on mechanisms that trade off short-term benefits for long-term harms. While some such risk is present in any medical intervention, we believe it is particularly pronounced for aging biology because the mechanisms targeted tend to be fundamental mechanisms of cell biology that may pervasively affect the whole organism. We propose a number of solutions – hallmarks to guide geroscience interventions – that should help minimize these risks while helping make progress.