To breathe or not to breathe: Understanding how oxygen sensing contributes to age-related phenotypes

Aging is characterized by a progressive loss of tissue integrity and functionality due to disrupted homeostasis. Molecular oxygen is pivotal to maintain tissue functions, and aerobic species have evolved a sophisticated sensing system to ensure proper oxygen supply and demand. It is not surprising that aberrations in oxygen and oxygen-associated pathways subvert health and promote different aspects of aging. In this review, we discuss emerging findings on how oxygen-sensing mechanisms regulate different cellular and molecular processes during normal physiology, and how dysregulation of oxygen availability lead to disease and aging. We describe various clinical manifestations associated with deregulation of oxygen balance, and how oxygen-modulating therapies and natural oxygen oscillations influence longevity. We conclude by discussing how a better understanding of oxygen-related mechanisms that orchestrate aging processes may lead to the development of new therapeutic strategies to extend healthy aging.