The stochasticity of biological aging

The recent Nature Medicine World View by M. Arfan Ikram¹ cites our article on the role of stochasticity in aging clocks as evidence for limited biological information from age predictors². Following a further Correspondence by Ferrucci et al.³, we find it important to clarify the roles of stochasticity in aging and in age prediction and to have an open debate on this topic.

The idea of aging as a genetically controlled process began with Cynthia Kenyon’s observation that a mutation in the daf-2 gene doubled the lifespan of worms. This led to the identification of mechanisms of aging that could be targeted genetically but also pharmacologically to slow the aging process. For example, treating mice with the mTOR inhibitor rapamycin extended lifespan⁴, and current clinical studies of the effects of GLP-1 receptor agonists have shown a reduction in age-related diseases, from heart disease to kidney disease⁵. In fact, the oldest lifespan-extending intervention, calorie restriction, was shown to provide beneficial effects on health in humans⁶.