Mitochondrial heterogeneity and crosstalk in aging: Time for a paradigm shift?

The hallmarks of aging have been influential in guiding the biology of aging research, with more recent and growing recognition of the interdependence of these hallmarks on age-related health outcomes. However, a current challenge is personalizing aging trajectories to promote healthy aging, given the diversity of genotypes and lived experience. We suggest that incorporating heterogeneity—including intrinsic (e.g., genetic and structural) and extrinsic (e.g., environmental and exposome) factors and their interdependence of hallmarks—may move the dial. This editorial perspective will focus on one hallmark, namely mitochondrial dysfunction, to exemplify how consideration of heterogeneity and interdependence or crosstalk may reveal new perspectives and opportunities for personalizing aging research. To this end, we highlight heterogeneity within mitochondria as a model.