Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review

Aging is associated with cellular and tissue decline, leading to conditions like neurodegenerative disorders, muscle weakness, and chronic diseases. In their study, Urolithin A as a Potential Agent for Prevention of Age-Related Disease: A Scoping Review, Kothe et al. explore Urolithin A (UA), a gut-derived metabolite produced from ellagitannins found in foods like pomegranates. The authors focus on UA’s role in improving mitochondrial function, a critical process in maintaining cell energy and health. By reviewing 15 key studies, they highlight UA’s potential in combating inflammation, oxidative stress, and mitochondrial dysfunction—factors that drive aging and age-related diseases such as Alzheimer’s, osteoporosis, and cancer. This scoping review sheds light on UA as a promising natural intervention for improving quality of life and longevity.

Aging is a natural process, but it comes with challenges like weaker muscles, memory loss, skin aging, and a higher risk of diseases such as osteoporosis and cancer. Scientists are now looking at natural compounds that might help slow down these changes.

One of these compounds is Urolithin A (UA), which is made in the gut when we eat foods rich in ellagitannins, like pomegranates and nuts. This scientific paper explores UA’s potential to improve aging health by boosting mitochondrial function and reducing inflammation.

The researchers thoroughly reviewed 293 studies using the PubMed and EMBASE databases. They specifically looked for papers that explored UA’s role in age-related diseases, focusing on studies conducted after 2017 to ensure up-to-date findings.

To ensure the results were clinically relevant, the team included only studies on human participants or human-derived cells. They excluded studies on animals, meta-analyses, systematic reviews, and editorials. After applying these criteria, 15 studies were chosen for detailed analysis. These included randomized controlled trials (RCTs) and in vitro experiments using human cells.

The researchers focused on how UA affects conditions like neurodegeneration, muscle and bone health, cardiovascular disease, skin aging, and cancer. They emphasized UA’s ability to improve mitochondrial health, a key factor in slowing aging.

Aging often leads to neurodegenerative diseases like Alzheimer’s. These conditions are linked to increased oxidative stress and inflammation in the brain. Several studies in the review found that UA could protect nerve cells by:

Reducing Inflammation

UA lowered levels of inflammatory markers like tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).

Fighting Oxidative Stress

UA treatment reduced the levels of harmful molecules called reactive oxygen species (ROS).

Improving Mitochondrial Health

UA boosted autophagy, the process that removes damaged mitochondria, helping cells work better.

One study noted, “UA pretreatment significantly reduced oxidative damage and cell death in neuronal models of Alzheimer’s disease.” Another experiment found that UA could protect neurons from damage caused by high blood sugar, which is often seen in diabetes-related brain problems.

As we age, our muscles weaken (a condition called sarcopenia ), and bones become brittle, increasing the risk of fractures. UA has been shown to help both muscle and bone health:

Muscle Strength and Endurance

In clinical trials, older adults who took 500-1,000 mg of UA daily for 28 days showed improved mitochondrial biomarkers and better performance on endurance tests.

Bone Health

UA reduced bone breakdown by lowering the activity of osteoclasts (cells that break down bone tissue). It also improved autophagy in bone cells, helping them stay healthy.

The researchers highlighted, “Supplementation with UA at 1,000 mg daily resulted in significant improvements in muscle endurance and reduced inflammatory markers such as C-reactive protein.”

Heart health often declines with age, especially in people with diabetes. The paper pointed out that UA may help reduce this risk by targeting pathways involved in heart disease:

Inhibiting the Akt Kinase Pathway

UA inhibited the Akt kinase pathway, which is overactive in diabetes and contributes to heart problems.

Reducing Atherosclerosis Risk

UA may reduce the risk of atherosclerosis, a condition where plaque builds up in the arteries.

Although most cardiovascular studies were conducted in animals, one human cell line study showed promising results: “UA significantly reduced Akt phosphorylation, suggesting potential benefits for diabetes-related cardiovascular complications.”

Our skin is one of the most visible signs of aging. With age, the skin loses firmness and becomes prone to damage from UV rays. UA was shown to combat these effects by:

Boosting Collagen Production

UA increased the production of type I collagen, which keeps skin firm and youthful.

Protecting Against UV Damage

UA treatment reduced DNA damage and oxidative stress in skin cells exposed to ultraviolet A (UVA) radiation.

One study noted, “UA prevented cellular senescence and enhanced antioxidant pathways, offering a promising anti-photoaging solution.”

Cancer risk increases with age, and UA shows potential as a natural way to slow cancer development. It works through several mechanisms:

Reducing Tumor Growth

UA decreased cancer cell proliferation and prevented tumor cells from spreading.

Promoting Autophagy and Apoptosis

UA helped clear damaged cells and induced programmed cell death in cancer cells.

A study on colorectal cancer cells found, “UA treatment led to a dose-dependent decrease in cancer cell migration and invasion, suggesting its role as an anti-cancer agent.”

Urolithin A is a natural compound found in foods like pomegranates, berries, and nuts. It supports mitochondrial health, addressing one of the main drivers of aging—cellular energy decline. This makes it a promising tool to combat a wide range of age-related problems, including muscle loss, brain decline, and chronic diseases.

In addition to improving muscle and bone health, UA’s ability to reduce inflammation and oxidative stress makes it especially useful for conditions like diabetes, Alzheimer’s, and cancer. The fact that UA is safe, well-tolerated, and derived from common foods adds to its appeal as a preventive health measure.

Urolithin A could transform how we age by targeting the root causes of age-related decline—damaged mitochondria and chronic inflammation. This study highlights its potential to improve muscle strength, protect the brain, fight cancer, and keep skin youthful.

Adding UA-rich foods to your diet or considering supplements could help maintain health and vitality as you age. However, more long-term human trials are needed to confirm its full benefits. For now, UA offers a natural and promising way to support healthy aging and improve quality of life.