The Gut-Muscle-Immune Axis: How Mitophagy Rewires Your Body for Longevity

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Are your immune cells aging faster than you are? In this episode, Dr. Gabrielle Lyon sits down with Dr. Anurag Singh, a leading physician-researcher and Chief Medical Officer at Timeline, to discuss a groundbreaking discovery: the gut-muscle-immune axis.

While we often focus on muscle mass for longevity, new research published in Nature Aging reveals that our immune system undergoes a similar decline, with youthful sentinel cells (naive CD8 T-cells) dropping by 75% as we reach age 50.

Dr. Singh explains how mitophagy —the targeted recycling of damaged mitochondria—is the key to "rewiring" an aging immune system to fight infection 20% more effectively. In this episode: Alzheimer’s of the Muscle: Why sporadic inclusion body myositis (sIBM) is often misdiagnosed as simple aging.

The Power of Urolithin A: How this postbiotic compound induces mitophagy to increase mitochondrial abundance by 20% in just 28 days. Immune Imprinting: Why children get 6-8 colds a year while adults only average 2-4. Repurposing Longevity Drugs: Dr. Singh’s take on Metformin, Rapamycin, and GLP-1s for life extension. The 1:1 Exercise Rule:Why 150 minutes of moderate activity is the threshold for mitochondrial biogenesis.

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Chapters:

0:00 - Can You Tell If Your Immune System Is Healthy?

1:37 - Alzheimer’s of the Muscle: Muscle-Immune Dysfunction

5:59 - The Thymus Design Flaw: Why Our Immune "Ammo" Disappears

8:44 - Naive CD8 T-Cells: The Elite Forces of Immunity

12:24 - The Axis of Aging: Mitochondria and Immune Cells in Muscle

16:15 - Mitophagy vs. Autophagy: Targeted Cellular Recycling

19:11 - Study Review: Rewiring the Immune System with Urolithin A

24:13 - Mitochondrial Remodeling: Switching from Glucose to Fatty Acids

27:45 - The Trifecta: Gut-Muscle-Immune Axis Connection

31:13 - Parkinson’s and the PINK1/Parkin Mitophagy Pathway

35:04 - Clinical Results: Improving Leg Strength in 4 Months

38:51 - Joint Health: Can We Remodel Cartilage with Mitophagy?

43:34 - Targeted Mitophagy Inducers: Exercise vs. Postbiotics

46:44 - Precision Nutrition: The Ideal Muscle Longevity Supplement

53:33 - Why Alzheimer’s is Now Considered an Inflammatory Disease

1:00:13 - The Placebo Effect: You Cannot Deceive the Immune System

1:03:13 - Lymphocyte Counts: The Clinical Marker for Immune Aging

1:08:14 - Rapamycin and Metformin: The Future of Longevity Drugs

1:11:42 - Optimal Dosing: Why 1,000mg of Urolithin A is the Standard

1:15:13 - Sports Medicine: Reducing Muscle Damage Markers (Creatine Kinase)

1:20:03 - The Final Frontier: Brain Aging and Selenium Repair

Connect with Dr. Anurag Singh

Instagram: @timeline_longevity

Website: https://www.timeline.com

Find Dr. Gabrielle Lyon at:

1. Instagram:@drgabriellelyon
2. TikTok: @drgabriellelyon