How This Peptide Drives Fat Loss & Preserves Muscle | Dr David Lee

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. Some links are affiliate links so we will earn a commission when they are used to purchase products. 🧬 SUPPORT THE CHANNEL & LONGEVITY PARTNERS If you would like to support our channel please consider joining our Patreon https://patreon.com/ModernHealthspan ~~~~~~~~~~~~~~ *Renue By Science* (10% off: MHS) https://tinyurl.com/bdew4bfs NMN Powder • Lipo NR *BiOptimizers* (15% off: MHBIO) https://bit.ly/47VAa8f - Magnesium Breakthrough, Gluten Guardian *Seeking Health* (10% off: Richard10) https://crrnt.app/SEEK/-dm0MyrQ, Histamine Nutrients https://crrnt.app/SEEK/EpM7paAO *Stemregen* (15% off: MODERN) *US only* https://tinyurl.com/45z968yr *AX3 Life* (20% off: MODERN20) https://ax3.life/MODERN20 - Astaxanthin *n1o1* (10% off: Modern) https://tidd.ly/3IczGRW - Nitric Oxide Lozenges *Qualia* (15% off: MODERN) Creatine+ https://tinyurl.com/mr3z35jd Senolytic https://bit.ly/4jlaibe *Qitone* (10% off: HEALTH10) https://tidd.ly/4jGklry Qitone Esters Powder *MitoQ* https://tinyurl.com/5n93fm3f MitoQ Pure https://tinyurl.com/3hxy9s7x *Wellness Extract* (10% off: MODERNWE) http://wellnessextract.com/RICHARDWE Geranylgeraniol • Vit E ~~~~~~~~~~~~~~ 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. 📚 *Chapters* 00:00:00 - Welcome Dr. David Lee 00:01:31 - What Are Mitochondrial-Derived Peptides? 00:07:01 - Evolutionary Origins & Cellular Stress Signaling 00:12:06 - How Exercise Induces MOTS-c & Hypothalamic POMC Neurons 00:17:09 - Metabolic Regulation, Protein Homeostasis & the ER 00:22:29 - MOTS-c Dynamics in Aging & Reversing Muscle Decline in Mice 00:30:01 - Chronic Adaptation vs. Acute Stress & Muscle Fiber Types 00:38:07 - Pharmacokinetics & Endogenous Half-Life 00:41:40 - MOTS-c as an Host Defense Peptide & Immunometabolism 00:50:31 - East Asian K14Q Gene Variant & Type 2 Diabetes Risk 00:56:02 - Human Clinical Trials, FDA 503A List & WADA Anti-Doping 01:03:08 - The Future of MOTS-c & Preventive Medicine *Educational & Informational Disclaimer:* This video and description are for educational, informational, and research entertainment purposes only and do not constitute medical advice, diagnosis, or treatment recommendation. MOTS-c and related mitochondrial-derived peptides (MDPs) remain investigational compounds. MOTS-c is not approved by the U.S. Food and Drug Administration (FDA) or international health authorities for human clinical use, prevention, or treatment of any disease. Discussing preclinical animal studies or early-phase translational trials does not imply safety or efficacy in humans. Always consult a qualified medical professional before altering any health, supplement, or therapeutic regimen. 🌐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 #Mots-c #Longevity #mitochondria