USC Gerontology Professor Dr. Changhan David Lee breaks down the discovery of MOTS-c, a novel mitochondrial-derived peptide that functions as an exercise mimetic, cellular stress responder, and immunomodulator. Are mitochondria more than just cellular powerhouses? In this episode of Modern Healthspan, Dr David Lee, Associate Professor at the USC Leonard Davis School of Gerontology and co-discoverer of MOTS-c, joins us for a deep dive into the emerging world of mitochondrial-derived peptides (MDPs). Dr. Lee explains how these small microproteins, encoded within the mitochondrial 12S rRNA locus, act as critical retrograde signaling molecules. We explore how MOTS-c translocates to the nucleus during metabolic stress, coordinates with AMPK and hypothalamic POMC neurons, and functions as an interferon-responsive host defense peptide. Additionally, Dr. Lee shares findings from preclinical models examining sarcopenia, muscle homeostasis, and age-related physical capacity, while providing an update on the current regulatory state, WADA anti-doping classification, and human translational pipeline of MDP research. 🌐Links in this video Dr David Lee's page at USC https://gero.usc.edu/faculty/lee/ 📚 References & Scientific Papers Mentioned: (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, 21(3), 443–454. https://pmc.ncbi.nlm.nih.gov/articles/PMC4350682/ (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications, 12(1), 470. https://www.nature.com/articles/s41467-020-20790-0 (2021). Mitohormesis in hypothalamic POMC neurons mediates regular exercise-induced high-turnover metabolism. Cell Metabolism, 33(2), 334–349. https://www.sciencedirect.com/science/article/pii/S1550413121000036 (2018). The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metabolism, 28(3), 516–524. (2021). Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes. Cell Reports, 36(4), 109447. MOTS-c Coordinates Inter-Organellar Proteostasis for Adaptation to Chronic Metabolic Stress https://www.biorxiv.org/content/10.64898/2026.06.22.733272v1 Qitone (10% off: HEALTH10) https://tidd.ly/4jGklry Qitone Esters Powder Seeking Health supplements: 10% discount code Richard10 https://crrnt.app/SEEK/-dm0MyrQ, Histamine Nutrients https://crrnt.app/SEEK/EpM7paAO AX3 Life Astaxanthin 20% discount code MODERN20 https://tinyurl.com/2t3w26nw https://www.choosemuse.com Stemregen 15% discount Code MODERN https://tinyurl.com/45z968yr (Only available in the US) Renue by Science all 10% discount with code MHS https://renuebyscience.com/ Nuchido Time+ 20% discount of first purchase with code MODERN20 https://nuchido.com/MODERN If you would like to support our channel please consider signing up on patreon https://patreon.com/ModernHealthspan You can also find us on YouTube at https://www.youtube.com/c/modernhealthspan
