MOTS-c (short for Mitochondrial Open Reading Frame of the 12S rRNA type-c) is a groundbreaking peptide that belongs to a new class of molecules known as mitochondrial-derived peptides (MDPs). Unlike most peptides that are encoded in the cell nucleus, MOTS-c is encoded within the mitochondrial genome—a rare and significant distinction. This peptide plays a vital role in cellular metabolism, stress response, and energy regulation, positioning it at the frontier of both longevity research and metabolic optimization.MOTS-c was first identified in 2015 by researchers at the University of Southern California, including Dr. Pinchas Cohen, during studies investigating non-nuclear genetic contributions to aging and disease resistance .

The discovery was revolutionary: it demonstrated that mitochondria can produce bioactive signaling peptides that regulate nuclear gene expression—essentially acting as messengers between mitochondria and the rest of the cell.One of the most important mechanisms of MOTS-c is its ability to activate AMPK (AMP-activated protein kinase), a key energy-sensing enzyme that promotes fatty acid oxidation, glucose uptake, and mitochondrial biogenesis. This makes MOTS-c functionally similar to exercise at the cellular level—earning it the nickname “exercise mimetic.” When energy levels are low (as in fasting or physical exertion), MOTS-c helps shift the cell’s metabolism toward greater energy efficiency, while also improving insulin sensitivity and glucose regulation. In animal models, MOTS-c has demonstrated impressive protective and performance-enhancing effects. One pivotal study showed that mice treated with MOTS-c had improved exercise capacity, greater resistance to diet-induced obesity, and enhanced insulin responsiveness . Another study showed that MOTS-c can protect cells from oxidative stress and delay the onset of age-related insulin resistance, supporting its potential role in healthy aging .

What makes MOTS-c particularly unique is:

• Its mitochondrial origin, offering a new biological pathway for metabolic intervention.
• Its broad spectrum of benefits, ranging from fat loss and metabolic balance to anti-inflammatory and longevity-enhancing properties.
• Its non-hormonal and well-tolerated profile, making it attractive for long-term use in aging and performance optimization.

In practical application, MOTS-c is being explored not just for fat metabolism and energy enhancement, but also as a therapeutic candidate for metabolic syndrome, type 2 diabetes, and age-related functional decline—with early results showing strong promise.