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As a naturally occurring protein hormone, MOTS-c is primarily activated by exercise or some type of stress, whereupon it translocates to the cells nucleus and mediates mitochondrial-nuclear communication.11 This crosstalk is crucial for coordinating the many mitochondrial functions and maintaining homeostasis.12 MOTS-c also activates the AMP-activated protein kinase (AMPK) pathway, a key regulator of cellular metabolism and homeostasis that helps produce energy by stimulating glucose uptake and fat oxidation.13 Much of this activity takes place in the skeletal muscles, which are rich in mitochondria because of their high energy demand.14 Over time, MOTS-c loses influence because its concentration declines with age.11 Consequently, people can become increasingly susceptible to some of the health conditions weve mentioned, many of which you may have noticed are largely age-correlated