Mitochondrial Peptides: Their Effect on Aging

Published 07/25/18

Mitochondria have long been recognized as the metabolic powerhouse in the body, and their functionality is critical to a number of processes. Interestingly, in recent years their role in signaling is being consistently appreciated. Thus, identifying reading frames that encode peptides has been a crucial component of research. One peptide that has been a huge area of interest is known as MOTS-c (mitochondrial open-reading-frame of the twelve S rRNA -c).

MOTS-c regulates insulin sensitivity and metabolic homeostasis. Its primary target organ appears to be the skeletal muscle and its cellular actions inhibit the folate cycle and its tethered de novo purine biosynthesis, leading to AMPK activation. MOTS-c treatment in mice prevented age-dependent and high-fat-diet-induced insulin resistance, as well as diet-induced obesity. MOTS-c targets the skeletal muscle and acts on the folate cycle (one carbon pool) and inhibits the directly tethered de novo purine biosynthesis pathway. This leads to the accumulation of the de novopurine synthesis intermediate AICAR that is also a potent activator of the metabolic regulator AMPK, thus partially mediating the metabolic effects of MOTS-c.

So, what kind of effect does this peptide have on the aging process?

Well, as you age, your metabolic efficiency decreases. This is indicated by a large drop in insulin sensitivity and decreased utilization of glucose for energy and metabolism. MOTS-c has been identified as a prominent signaling peptide that gets activated when stress or age take effect on mitochondrial cells, acting to return the body to metabolic homeostasis. It has been shown that mutations in mitochondrial DNA and consequent metabolic dysfunction are strongly indicated in aging. Interestingly, as you age and mitochondrial function decreases, the circulating levels of MOTS-c fall quite dramatically. Further, there have been studies that suggest profound systemic effects of the administration of MOTS-c in mice. So, there is extreme potential for this mitochondrial peptide because it may reverse the abnormal metabolism associated with age.