Metabolism, homeostasis, and aging

Metabolism can be categorized by resource abundance or depletion.Resource abundance drives the pursuit type of metabolism and consists of anabolism and catabolism.Resource depletion, accompanied by metabolic waste accumulation as a result of pursuit, activates the maintenance type of metabolism and consists of damage pre-emption and clearance mechanisms.The organismal sensory system mediates pendulum-like swings between pursuit and maintenance states in an attempt to sustain the least deleterious state: homeostasis.Swings represent imperfect metabolic reactions and generate deleterious metabolic consequences.Adjusting environmental signals close to neutral may lower the magnitude of metabolic swings, extend the periods near the homeostatic point, and extend lifespan.Analyzing pathways activated by metabolic waste could help to identify new interventions to slow aging. We propose a two-mode (pursuit/maintenance) model of metabolism defined by usable resource availability. Pursuit, consisting of anabolism and catabolism, dominates when usable resources are plentiful and leads to the generation of metabolic waste. In turn, maintenance of a system is activated by elevated metabolic waste during resource depletion. Interaction with the environment results in pendulum-like swings between these metabolic states in thriveless attempts to maintain the least deleterious organismal state – ephemeral homeostasis. Imperfectness of biological processes during these attempts supports the accumulation of the deleteriome, driving organismal aging. We discuss how metabolic adjustment by the environment and resource stabilization may modulate healthspan and lifespan.