Evolutionarily conserved transcription factors as regulators of longevity and targets for geroprotection

Abstract

Aging is the single largest risk factor for many debilitating conditions, including heart diseases, stroke, cancer, diabetes, and neurodegenerative disorders. Although far from understood in its full complexity, it is scientifically well established that aging is influenced by genetic and environmental factors and can be modulated by various interventions. One of aging’s early hallmarks is aberrations in transcriptional networks, controlling for example metabolic homeostasis or the response to stress. Evidence in different model organisms abounds that a number of evolutionarily conserved transcription factors, which control such networks, can affect life span and health span across species. These transcription factors thus potentially represent conserved regulators of longevity and are emerging as important targets in the challenging quest to develop treatments to mitigate age-related diseases, and possibly even to slow aging itself. This review provides an overview of evolutionarily conserved transcription factors that impact longevity or age-related diseases in at least one multicellular model organism (nematodes, flies, or mice) and/or are tentatively linked to human aging. Discussed is the general evidence for transcriptional regulation of aging and disease, followed by a more detailed look at selected transcription factor families, the common metabolic pathways involved, and the targeting of transcription factors as a strategy for geroprotective interventions.