What Causes Mitochondrial Decline?

Mitochondrial function tends to slip as we age, and it rarely comes down to a single cause. It is the accumulation of small hits over decades — damage that outpaces repair, quality-control systems that slow down, and lifestyle patterns that add strain — that gradually lowers the efficiency of the cell's power plants.

A quick primer: what "decline" actually means

Mitochondria convert nutrients and oxygen into ATP, the energy molecule that powers nearly everything cells do. "Mitochondrial decline" is shorthand for a cluster of changes that researchers observe with age: fewer functional mitochondria in some tissues, individual mitochondria that produce energy less efficiently, more damaged components accumulating inside them, and a slowdown in the housekeeping systems that normally keep the whole population healthy. Importantly, this is a description of a gradual, normal aging process — not a disease diagnosis. Rare inherited mitochondrial diseases are a separate medical category managed by physicians.

The main drivers of age-related mitochondrial decline

The scientific literature points to several overlapping mechanisms. No single one tells the whole story; they reinforce one another over time.

1. Accumulated oxidative damage

Producing energy is inherently a little messy. As mitochondria generate ATP, they also produce reactive oxygen species (ROS) as a byproduct. In modest amounts, ROS act as useful signaling molecules. In excess, and over many years, they can damage mitochondrial proteins, lipids, and the mitochondria's own DNA. Because mitochondrial DNA sits close to where ROS are generated and has less protective machinery than the DNA in the cell nucleus, it is particularly vulnerable to accumulating small errors. Over a lifetime, this damage-and-repair imbalance is one widely studied contributor to declining efficiency.

2. A slowdown in mitophagy — the quality-control system

This is the mechanism most relevant to urolithin A, so it is worth understanding well. Cells have a dedicated recycling process called mitophagy: worn-out or underperforming mitochondria are tagged, dismantled, and their parts reused, making room for healthier mitochondria to take their place. Think of it as ongoing fleet maintenance — retiring the vehicles that break down often so the fleet as a whole stays reliable. Research indicates that mitophagy tends to become less efficient with age. When the recycling slows, damaged mitochondria linger longer, drag down the average performance of the population, and can generate more ROS — a self-reinforcing loop. The foundational work establishing mitophagy's role in mitochondrial and muscle aging (Ryu et al., 2016, Nature Medicine) was done in worms and rodents and is preclinical, so it describes mechanism rather than proven human outcomes.

3. Reduced mitochondrial biogenesis

Alongside recycling old mitochondria, cells build new ones — a process called biogenesis, driven partly by signals triggered during exercise. The capacity to build new mitochondria can decline with age, and it also falls with disuse. This is one reason a sedentary lifestyle and the natural loss of muscle over time (sarcopenia) are so closely tied to the energy changes people notice as they get older: less demand and less stimulus mean fewer signals to build and maintain the machinery.

4. Lifestyle and environmental strain

On top of the intrinsic biology, everyday factors add load. Chronic inactivity reduces the biogenesis signal. Poor sleep limits repair time. Diets heavy in ultra-processed foods and low in colorful plants provide less of the polyphenols and micronutrients that research is exploring for metabolic support. Excess body fat, chronic stress, smoking, and heavy alcohol intake are all associated in the literature with added oxidative and inflammatory burden. None of these is a switch that flips overnight — they are cumulative pressures that either accelerate or slow the underlying trajectory.

5. "Inflammaging" and the immune connection

Aging is accompanied by a low-grade, chronic uptick in inflammation that researchers call inflammaging, and mitochondrial health in immune cells appears to be part of that picture. A 2025 randomized trial in Nature Aging (roughly 28 days) reported that urolithin A supported immune-cell mitochondrial health in midlife adults — an emerging but genuinely human finding that adds a new dimension to how we think about mitochondrial aging beyond muscle alone.

Where urolithin A fits into this picture

Urolithin A is a gut postbiotic: your microbiome produces it from ellagitannins, the compounds found in pomegranates, walnuts, and certain berries. Its scientific interest centers on the second driver above — it supports mitophagy, the recycling process that tends to slow with age. In other words, rather than trying to add energy directly, urolithin A is studied for supporting the cell's own quality-control step.

Here is the human evidence, organized by strength and clearly separated from the animal work:

Human trials (strongest evidence)

The first-in-human study (Andreux et al., 2019, Nature Metabolism) found urolithin A safe and well tolerated up to 1,000 mg per day and detected a mitochondrial gene-expression signature. In older adults over roughly four months, it supported muscle endurance measured as contractions before fatigue (Liu and D'Amico et al., 2022, JAMA Network Open). In middle-aged adults, both 500 mg and 1,000 mg arms supported muscle strength and exercise performance (Singh et al., 2022, Cell Reports Medicine). An 8-week randomized trial in resistance-trained men examined endurance and recovery markers (Journal of the International Society of Sports Nutrition, 2024), and the 2025 Nature Aging trial addressed immune-cell mitochondrial health.

Preclinical research (mechanism, not human proof)

The original mitophagy and lifespan findings (Ryu et al., 2016, Nature Medicine) come from C. elegans and rodents. Work on joint and cartilage mitochondrial health in osteoarthritis models (D'Amico et al., 2022, Aging Cell) is likewise preclinical. Early research is also exploring roles in skin, gut, brain, and heart tissue — all of which should be read as "exploring," not established in humans.

Honest limitations

A 2024 systematic review in Ageing Research Reviews concluded that the human evidence for urolithin A in aging is still emerging, drawn from relatively short trials with modest sample sizes. That is the fair reading: promising mechanism, a growing but early human dataset, and no basis for treatment claims. Our clinical studies overview and the full urolithin A guide lay this out in detail, and our mitophagy explainer covers the mechanism.

Not a treatment — see your doctor. Mitochondrial decline is a normal feature of aging, not a disease to self-treat. Urolithin A and the habits described here are intended to support normal mitochondrial, muscle, and metabolic health — not to treat, reverse, or prevent any medical condition. Symptoms that are new, severe, or persistent deserve evaluation by a qualified healthcare provider.

What you can actually do about it

The levers with the deepest evidence are behavioral. Exercise — both aerobic and resistance training — is the most reliable stimulus for building and maintaining mitochondria, and it also helps offset the age-related loss of muscle that drives so much of the change. Prioritizing sleep protects repair time. A diet built around colorful plants, adequate protein, and whole foods supplies raw materials and polyphenols; our guide to foods for mitochondrial health is a practical starting point. Reducing avoidable strain — excess alcohol, smoking, chronic sleep debt — removes headwinds. Against that foundation, a standardized urolithin A supplement is a targeted addition for the mitophagy step, not a replacement for any of it. If you are choosing a product, our best urolithin A gummies roundup compares the options.

The SOMA HEALTH approach

SOMA HEALTH Urolithin A Gummies provide 1,000 mg per four-gummy daily serving — the top of the clinically studied 500–1,000 mg range — in a 30-day supply of 120 raspberry, sugar-free gummies, each batch third-party tested. It is a precise, well-characterized dose in a format that is easy to sustain, designed to sit alongside the movement, sleep, and nutrition that address mitochondrial decline at its roots.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. This guide is educational and is not a substitute for advice from a qualified healthcare provider.