The Role of Mitochondrial Health in Aging

Mitochondrial health matters for aging because mitochondria produce most of the energy your cells use, and their efficiency tends to decline with age, contributing to fatigue, muscle loss and metabolic disease. Scientists now list mitochondrial dysfunction as one of the recognized hallmarks of aging. The strongest evidence for improving mitochondrial function in people comes from exercise, not from supplements or peptides.

What Mitochondria Do

Mitochondria are small structures inside nearly every cell. Their best-known job is converting the food you eat and the oxygen you breathe into ATP, the cell's energy currency. They also:

• Help regulate blood sugar and fat metabolism
• Produce signaling molecules, including small amounts of reactive oxygen species that act as useful messages
• Control calcium balance inside cells
• Help decide when a damaged cell should die

Tissues with high energy demand, such as heart, brain, muscle and kidney, are packed with mitochondria. That is why mitochondrial problems often show up as fatigue, exercise intolerance or reduced organ reserve.

How Mitochondrial Health Changes With Aging

In 2023, a widely cited scientific review updated the "hallmarks of aging," a framework describing the biological processes that drive aging. Mitochondrial dysfunction is one of them. The changes typically described include:

• Less efficient energy production, with more electrons "leaking" and generating excess oxidative stress
• Accumulated mitochondrial DNA damage, since mitochondria carry their own small genome
• Reduced mitophagy, the cleanup process that removes damaged mitochondria
• Lower mitochondrial biogenesis, meaning fewer new mitochondria are built
• Declining NAD+ levels, a coenzyme central to energy metabolism

These processes interact with other hallmarks, including chronic inflammation, cellular senescence and impaired nutrient sensing. Importantly, much of this research comes from animal models and tissue studies. How much each factor drives human aging, and how much is a consequence of inactivity and disease, is still being worked out.

What the Evidence Supports Most

Exercise

Exercise is the most powerful, best-studied way to improve mitochondrial health in humans. Training stimulates mitochondrial biogenesis, improves the efficiency of existing mitochondria and enhances mitophagy. Both forms matter:

• Aerobic training, including steady moderate work and higher-intensity intervals, increases mitochondrial content in muscle. A practical approach is described in Zone 2 Cardio: The Longevity Exercise Protocol.
• Resistance training preserves muscle mass, which is where much of the body's mitochondrial capacity lives.

Metabolic health

Chronically elevated glucose and insulin, excess visceral fat and fatty liver are all associated with impaired mitochondrial function. Treating prediabetes, losing excess visceral fat and controlling blood pressure support mitochondria indirectly but meaningfully.

Sleep and recovery

Poor sleep impairs glucose metabolism and recovery from training. Untreated sleep apnea, in particular, exposes tissues to repeated drops in oxygen.

Alcohol, smoking and medications

Alcohol and smoking both injure mitochondria. Some medications also affect mitochondrial function, which is one reason a physician-led medication review matters.

Newer Compounds: What Is Known and Unknown

Interest in mitochondria-targeted therapies is growing. Here is an honest summary:

• NAD+ precursors (such as NMN and nicotinamide riboside): Human studies show they raise NAD+ levels and are generally well tolerated in the short term. Clear benefits on aging outcomes have not been demonstrated. FDA allows NMN to be sold as a dietary supplement, which means it is not reviewed for effectiveness. See NAD Therapy: Injections vs. Capsules vs. IV.
• SS-31 (elamipretide): Binds cardiolipin in the inner mitochondrial membrane. It received FDA accelerated approval in September 2025 for Barth syndrome, a rare inherited mitochondrial disease. Use for aging is not established. More in SS-31 (Elamipretide): The Mitochondrial Protector.
• MOTS-c: A peptide encoded by mitochondrial DNA that appears to act on metabolism. Evidence is largely limited to animal studies. It is not FDA-approved, and its compounding status is under FDA review as of this writing.
• SLU-PP-332: A small molecule, not a peptide, promoted as an "exercise mimetic." Data are from mice only.
• Urolithin A and similar mitophagy activators: Small human trials exist with modest effects on some muscle measures; long-term benefits are unknown.

None of these replaces training. Where they have a role, it is as a carefully considered adjunct after the foundation is in place, discussed only after evaluation and labs, with dosing individualized rather than taken from online protocols.

How I Assess Mitochondrial Health in Practice

There is no single routine test for mitochondrial function. In my practice, I start with labs and functional measures that reflect it indirectly:

• Fasting glucose, hemoglobin A1c and sometimes fasting insulin
• Lipid patterns, including triglycerides
• Liver enzymes and imaging when fatty liver is suspected
• Thyroid function, iron studies and B12, which affect energy
• Fitness measures, such as an estimate of aerobic capacity and strength
• Sleep history and, when indicated, sleep apnea testing

If an inherited mitochondrial disease is suspected, that requires specialist evaluation and genetic testing, which is a different conversation from age-related decline.

The Bottom Line

Mitochondrial health is a real and important part of how we age. The science is fascinating, and new therapies are emerging, but the best human evidence still points to exercise, metabolic health and sleep. At Laeeq M.D., we build that foundation first and discuss newer options with honest framing about what is proven and what is not.

Sources

• López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. "Hallmarks of aging: An expanding universe." Cell, 2023. https://doi.org/10.1016/j.cell.2022.11.001
• US Food and Drug Administration. "FDA Grants Accelerated Approval to First Treatment for Barth Syndrome." FDA, 2025. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-treatment-barth-syndrome

Book a Consultation

If low energy, declining fitness or metabolic changes concern you, a structured evaluation is the best place to begin. You can book a consultation with Dr. Laeeq for a 60-minute visit, virtual or in person in Reston, VA, to review your labs and build a plan grounded in evidence.

This article is for educational purposes and is not medical advice. Discuss any treatment with a licensed physician who knows your history.