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

Jan 6, 2026

Dr. Anurag Singh, a physician-researcher and Chief Medical Officer at Timeline, shares his insights into groundbreaking research on mitophagy and the gut-muscle-immune axis. He reveals how mitophagy enhances immune cell efficiency and discusses the decline of naive CD8 T cells with age. Dr. Singh explains the benefits of urolithin A for mitochondrial health and its remarkable effects on immune function and longevity. Tune in to discover how exercise and dietary strategies can optimize your cellular health!

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INSIGHT

Thymus Decline Shrinks Immune Ammo

Lymphocyte counts and total leukocytes decline with age, reducing immune surveillance.
The thymus involutes after adolescence, limiting new T-cell generation and creating long-term immune vulnerability.

INSIGHT

Naive CD8 Cells Fall Sharply By Midlife

Naive CD8 T cells — the youthful frontline responders — drop dramatically starting around age 40–50.
This loss leaves only about 25% of youthful CD8 capacity compared with young adulthood.

INSIGHT

Muscle Mitochondria And Immunity Are Linked

Skeletal muscle aging shows two parallel hallmarks: mitochondrial dysfunction and immune cell dysregulation.
Those two processes form an axis where decline in one worsens the other in muscle health.

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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.

Thank you to our sponsors:

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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:

Instagram:@drgabriellelyon
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Join my weekly newsletter – https://institute-for-muscle-centric-medicine.ck.page
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Disclaimers: This episode includes paid sponsorships.

The Dr. Gabrielle Lyon Podcast and YouTube are for general information purposes only and do not constitute the practice of medicine, nursing, or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this podcast, YouTube, or materials linked from this podcast or YouTube is at the user's own risk. The content of this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they may have and should seek the assistance of their health care professional for any such conditions.