Biomarkers of healthy ageing: expectations and validation

The challenge of devising a set of biomarkers capable of measuring the ageing rate in human subjects was articulated long ago. In recent years, progress in the basic biology of ageing suggests the realistic possibility of preventive or restaurative interventions that may extend healthy lifespan in mammals including human subjects. Specifically, frailty is being increasingly recognised as a clinically relevant syndrome that may be therapeutically addressed. This greatly enhances the need for sensitive and specific biomarkers of healthy ageing that are validated in both experimental animals and, importantly, in human subjects over the whole age range. Here, we will discuss the present challenges and requirements for biomarker validation in human subjects. We propose the central requirements for a validated biomarker of healthy ageing as: (i) better predictive power than chronological age for multiple dimensions of ageing; (ii) identification of the age range in which the marker is informative; (iii) establishment of sensitivity/specificity as indicators of its predictive power at the level of the individual; (iv) minimisation of methodological variation between laboratories.