Approaches for extending human healthspan: from antioxidants to healthspan pharmacology

Abstract

Dramatic increases in human lifespan and declining population growth are monumental achievements but these same achievements have also led to many societies today ageing at a faster rate than ever before. Extending healthy lifespan (healthspan) is a key translational challenge in this context. Disease-centric approaches to manage population ageing risk are adding years to life without adding health to these years. The growing consensus that ageing is driven by a limited number of interconnected processes suggests an alternative approach. Instead of viewing each age-dependent disease as the result of an independent chain of events, this approach recognizes that most age-dependent diseases depend on and are driven by a limited set of ageing processes. While the relative importance of each of these processes and the best intervention strategies targeting them are subjects of debate, there is increasing interest in providing preventative intervention options to healthy individuals even before overt age-dependent diseases manifest. Elevated oxidative damage is involved in the pathophysiology of most age-dependent diseases and markers of oxidative damage often increase with age in many organisms. However, correlation is not causation and, sadly, many intervention trials of supposed antioxidants have failed to extend healthspan and to prevent diseases. This does not, however, mean that reactive species (RS) and redox signalling are unimportant. Ultimately, the most effective antioxidants may not turn out to be the best geroprotective drugs, but effective geroprotective interventions might well turn out to also have excellent, if probably indirect, antioxidant efficacy.