Oxygen and Aging

Abstract

Oxygen is a double-edged sword. Despite the near universal requirement for oxygen for survival and reproduction in animals, oxygen and oxidative metabolism are responsible for the production of reactive oxygen species (ROS), which has, until recently, been considered a cellular toxin and a major cause of aging. Alterations in environmental oxygen can alter rates of aging and ROS production in many organisms. Animals coordinate the cellular response to low oxygen with a conserved hypoxic response mediated by the hypoxia inducible transcription factor, hypoxia-inducible factor (HIF). In addition to hypoxia, HIF has been shown to have roles in aging, cancer, cardiovascular disease, and stem cell maintenance in organisms from worms to humans. Furthermore, HIF has been shown to interact with mechanistic target of rapamycin (mTOR), Sirtuins, and to infl uence other pathways and interventions known to affect the aging. This chapter focuses on the effects of altered oxygen concentrations on the aging, its similarities to dietary restriction, how mutations in the HIF pathway affect lifespan and health span, and how the HIF pathway interacts with other conserved longevity pathways.

Intermittent hypoxia therapy engages multiple longevity pathways to double lifespan inC.elegans

“…Mitochondria are the primary consumers of molecular oxygen in the cell and mitochondrial dysfunction is one of the key hallmarks of aging( 36 ). The role of oxygen in the aging process, primarily as a putative source of damaging ROS has been hypothesized for decades, however low oxygen therapies have shown limited results in increasing longevity( 37 ). Our results suggest that organismal responses to low oxygen are complex, and that sensory or reproductive signals triggered by acute hypoxia exposure, rather than decreased total lifetime oxygen levels, can trigger endogenous protective pathways to dramatically increase lifespan in wildtype animals.…”

Effects of Hyperoxia on Aging Biomarkers: A Systematic Review

“…More recently, numerous studies have indicated a more important role of HIF-1α as a direct modulator of aging. Studies have shown that HIF-1α significantly increases the life span of adult Caenorhabditis elegans ( Cypser and Johnson, 2002 ; Pitt et al, 2014 ). In addition to modulating aging, the HIF-1α pathway is also interrelated with other aging pathways, such as mechanistic target of rapamycin (mTOR), insulin-like signaling, and dietary restriction ( Pitt et al, 2014 ).…”