The metabolome as a biomarker of aging in Drosophila melanogaster

Many biomarkers have been shown to be associated not only with chronological age, but also with functional measures of biological age. It is difficult to show in human populations though, whether variation in biological age is truly predictive of life expectancy, as it requires longitudinal studies over many years and possibly decades. We followed adult cohorts of 20 Drosophila Genetic Reference Panel (DGRP) strains chosen to represent the breadth of lifespan variation, obtaining estimates of lifespan, baseline mortality and rate of aging, and associated these parameters with age-specific functional traits including fecundity and climbing activity, and with age-specific targeted metabolomic profiles. We show that activity levels as well as metabolome-wide profiles are strongly associated with age, that numerous individual metabolites show a strong association with lifespan, and that the metabolome provides a biological clock that not only predicts sample age, but also future mortality rates and lifespan. This study, while relatively small in scope with 20 genotypes and 87 metabolites, establishes strong proof of principle for the fly as a powerful experimental model to test hypotheses about biomarkers and aging, and provides further evidence for the potential value of metabolomic profiles as biomarkers of aging.