Mitochondria Peptides: MOTS-c, Humanin, Genetic Variation in Health & Disease | Pinchas Cohen | Episode 304

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Mitochondrial peptides act as stress signals that regulate metabolism, muscle mass, and neurodegeneration.

TOPICS DISCUSSED:

• Mitochondria as Communication Hubs: Beyond ATP production, mitochondria encode peptides that regulate cell death, immunity, and inter-organ communication.
• Humanin Discovery: Identified independently by three labs; neuroprotective, longevity-linked, and capable of neutralizing APOE4 effects via a rare Jewish variant.
• Ethnic Genetic Variants: Ancestry-specific mutations in MOTS-c, MENTSH, and SHMOOSE influence diabetes, obesity, sarcopenia, and Alzheimer’s risk.
• MOTS-c & Muscle Preservation: Exercise-induced peptide prevents atrophy and may offset muscle loss seen with GLP-1 drugs.
• Peptide Classes: Fragments of larger proteins, endogenous microproteins from small genes, and emerging AI-designed artificial peptides.
• Diet Modulation: Mediterranean diet adherence raises circulating levels of the peptides humanin and SHMOOSE.
• Clinical Reality Check: Early MOTS-c trials showed metabolic benefits; unregulated products often contain inaccurate doses.

ABOUT THE GUEST: Pinchas Cohen, MD is Dean of the USC Leonard Davis School of Gerontology and a leading researcher on mitochondrial peptides in aging, metabolism, and neurodegeneration.

RELATED CONTENT:

• Article | Metabolic Stress & the Peptide MOTS-c: How Much is Too Much?
• Podcast | MOTS-c & Mitochondrial Peptides in Health & Aging | David Lee

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