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“Diet and exercise will help you live longer” is a well-known meme. While often taken for granted, its foundations span back to our evolutionary environment and its effects extend into our intracellular environment. Humans evolved under conditions of high physical activity and periodic privation which shaped our genes. During these times of energetic challenge, an evolutionary conserved recycling system, autophagy, would have been activated to provision energy through the degradation of intracellular proteins, organelles, and lipids. With physical activity no longer a requisite for survival and caloric abundance rather than caloric shortage defining the modern human environment, the signals for autophagy are no longer obligatory. Moreover, humans have evolved an avoidance of physical activity and caloric restriction (CR). This leads to an accumulation of intracellular components causing degeneration and disruption of cellular homeostasis. This deleterious accrual of cellular materials also occurs during aging, in part, by an age-related decline in autophagy. What’s more, humans live in a period of history where advances in sanitation and medicine have allowed us to live to unprecedented ages, resulting in long-lived humans with progressive system-wide degeneration. Exercise and CR practices promote age-related health and longevity through their activation of autophagic housekeeping, but evolutionary inertia pushes us to avoid them. However, humans are unique in that we can harness our own genes as well as propagate our own memes. In order to yield the benefits of cellular housekeeping through exercise and CR practices, we should understand our genes and become memesters.

“Diet and Exercise Will Help You Live Longer”: The Meme that Turns on Housekeeping Genes