This study explores how supplementation with the mitophagy activator Mitopure (Urolithin A) enhances mitochondrial activity in immune cells (T-cells) in healthy adults, addressing immune aging and inflammaging, and ultimately improving long-term immune function.

Urolithin A (Mitopure®), administered topically, significantly reduces wrinkles, improves skin hydration, and decreases UV-induced erythema. It up-regulates collagen synthesis pathways, inhibits collagen degradation, and enhances mitophagy and autophagy in skin cells. These results support the use of Urolithin A to manage skin health and protect against skin aging and UVB-mediated photodamage.

A double-blind, placebo-controlled study shows that Urolithin A (Mitopure) significantly improves muscle strength (∼12%). Researchers observe clinically meaningful improvements with Urolithin A on aerobic endurance (peak oxygen oxygen consumption [VO2]) and physical performance (6 min walk test) but do not notice a significant improvement on peak power output (primary endpoint). Plasma acylcarnitines and C-reactive proteins were significantly lower, indicating higher mitochondrial efficiency and reduced inflammation. Urolithin A also increased protein expression linked to mitophagy and mitochondrial metabolism in skeletal muscle.

Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA), complex polyphenols abundant in foods such as pomegranate, berries and nuts. UA was discovered 40 years ago, but only recently has its impact on aging and diseases been explored. UA enhances cellular health by increasing mitophagy and mitochondrial function and reducing detrimental inflammation. Several preclinical studies show how UA protects against again and age-related conditions affecting muscle, brain, joints, and other organs. In humans, benefits of UA supplementation in the muscle are supported by recent clinical trials in elderly people. Here, we review the state of the art of UA's biology and its translational potential as a nutritional intervention in humans.

This is a randomized, double-blind, placebo-controlled trial found that urolithin A (Mitopure) supplementation was safe and well tolerated in adults aged 65 to 90 years. Although the improvements in the 6-minute walk distance and maximal ATP production in the hand muscle were not significant in the urolithin A group vs the placebo group, long-term urolithin A supplementation (1,000 mg Mitopure) was beneficial for muscle endurance and plasma biomarkers, suggesting that urolithin A may counteract age-associated muscle decline.

This study investigated the prevalence of Urolithin A (UA) producers in a healthy population and the effectiveness of direct UA supplementation with Mitopure to overcome microbiome and dietary variability. Only 12% of subjects had detectable levels of UA at baseline. Following pomegranate juice intake, ~40% of the subjects converted precursor compounds into UA. UA producers had higher gut microbiome diversity and were distinguished by a higher ratio of Firmicutes to Bacteroides. Direct UA supplementation significantly increased plasma levels and provided >6-fold exposure compared to pomegranate juice.

We report the results of a first-in-human clinical trial in which we administered Urolithin A (Mitopure), either as a single dose or as multiple doses over a 4-week period, to healthy, sedentary elderly individuals. We show that Urolithin A (UA) has a favourable safety profile (primary outcome). UA was bioavailable in plasma at all doses tested, and 4 weeks of treatment with UA at doses of 500 mg and 1,000 mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elderly individuals (secondary outcomes). These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.

This clinical study evaluated mitochondrial (dys)function in pre-frail elderly (>60 years) compared to age-matched active elderly. Results showed impaired phosphocreatine recovery, lower mitochondrial respiratory complex protein and activity levels, and down-regulated mitochondrial genes in pre-frail individuals. Findings suggest that mitochondrial impairment is a key factor in pre-frailty development and muscle function decline in the elderly, highlighting potential targets for preventative interventions.

This is a randomized, double-blind, placebo-controlled study enrolling 36 (16 Elite and 20 Sub-Elite trained endurance runners (18 placebo and 18 Mitopure intervention) who are 18-40 years of age. Mitopure or Placebo supplement, will be given as a daily oral dose for 4-weeks.

Open labelled, virtual home based study to assess the test repeatability and the failure/rejection rate of the samples collected at home by participants.

The goal of the biological sample collection is to assess the presence of gut metabolites in human breast milk (BM) samples obtained prospectively from healthy lactating mothers and after consumption of fruit juice.

This study in Nature Aging, from researchers of the University of Lausanne (UNIL), the Lausanne University Hospital (CHUV) and the Ludwig Institute for Cancer Research, in Switzerland, uncovers the pivotal role of hematopoietic stem cells (HSCs) in immune health and potential link to healthy aging. As we age, these cells, crucial for our immune system, show diminished functionality. Interestingly, the team uncovered a potential solution: Urolithin A, a natural compound. Targeting mitochondria, which were identified as a factor in HSC aging, Urolithin A rejuvenated the cells by restoring their mitochondrial function.

This study looked at the biological effects of UA in C. elegans (worms) and rodents to assess the health benefits. In C. elagans, UA prolonged lifespan and normal activity during aging. In rodents, UA improved exercise capacity in models of age-related muscle decline. These findings demonstrate the positive effects of UA and its potential role in strategies to improve mitochondrial function and muscle health.

This study showed that treatment with Amazentis’ proprietary Urolithin A supplement, Mitopure, significantly improved the cancer-fighting properties of T-cells, a key part of the immune system. Urolithin A renewed the energy factories of the T-cells via a cellular recycling pathway called mitophagy and so helped maintain their anti-cancer activity for longer, the research shows. These findings further highlight Urolithin A’s potential benefits for immune aging and cancer management.

OA affects 500M+ people worldwide with no effective therapy. Mitochondrial dysfunction contributes to OA pathology, but no interventions to rescue mitochondrial defects in human OA are available. Urolithin A (Mitopure) is a natural compound that promotes mitophagy and mitochondrial function. It improved mitophagy and mitochondrial respiration in primary chondrocytes from joints of healthy donors and OA patients. It also reduced disease progression in a mouse model of OA, decreasing cartilage degeneration, synovial inflammation, and pain, indicating UA's potential to improve mobility and alleviate OA pathology.

Mitochondrial dysfunction has been implicated in Duchenne muscular dystrophy (DMD). Luan and colleagues studied the role of mitophagy (mitochondrial autophagy) in muscle stem cells and DMD. Mitophagy was reduced in muscle biopsies from patients with muscular dystrophies and in mouse and worm models of DMD. Urolithin A, a mitophagy activator, up-regulated mitophagy-related genes and improved mitochondrial respiration, muscle stem cell regeneration and muscle function in models of DMD. This demonstrates how enhancing mitophagy could potentially help treat DMD.