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Metabolism, homeostasis, and aging

Journal

TRENDS IN ENDOCRINOLOGY AND METABOLISM
Volume 34, Issue 3, Pages 158-169

Publisher

CELL PRESS
DOI: 10.1016/j.tem.2023.01.003

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We propose a two-mode model of metabolism, which includes pursuit (anabolism and catabolism) and maintenance, based on usable resource availability. Pursuit dominates when resources are abundant, generating metabolic waste, while maintenance is activated when resources are depleted and metabolic waste accumulates. Interactions with the environment cause pendulum-like swings between these metabolic states, attempting to maintain the least deleterious organismal state, known as ephemeral homeostasis. Imperfections during these attempts contribute to the accumulation of harmful effects, driving organismal aging. We discuss how environmental metabolic adjustments and resource stabilization can impact healthspan and lifespan.
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 met-abolic 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. Im-perfectness of biological processes during these attempts supports the accumu-lation of the deleteriome, driving organismal aging. We discuss how metabolic adjustment by the environment and resource stabilization may modulate healthspan and lifespan.

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