The Role Of Oxidative Signaling In Longevity & Aging

Basal levels of reactive oxygen species (ROS) are necessary for normal stress response physiology. Insufficient ROS is detrimental and associated with decreased longevity.  Stress challenges induce an increase in ROS from basal levels. These transient increases in ROS have a biphasic relationship to the stress response and drive both pro and anti-longevity effects depending on whether the ROS challenge lies within a homeodynamic range of the stress response.  If the ROS challenge is within the homeodynamic range, then oxidative signaling mediates beneficial effects to promote longevity as evidenced by an improvement in cellular health markers.  Increased overall cell health leads to an expansion of the homeodynamic range and an increase in resilience to subsequent stress challenges.  These homeostatic ROS increases originate from good types of stress, referred to as "eustress", such as stress induced from exercise or cold shock.  However, if excessive ROS lies outside the homeodynamic range, it has a "distress" effect on the stress response.  In distress, the stress response fails to resolve cellular stress leaving unfulfilled cellular demand.  In aging, chronic distress shrinks the homeodynamic range, leaving cells weaker to remediate subsequent stress challenges, and ultimately driving a decline towards frailty, aging and neurodegenerative diseases.