Dead Mitochondria Might Be Fueling Cardiovascular Aging — Here’s The Fix

David Demoiko's team at Timeline, in collaboration with the University of Washington, tested urolithin A in mouse models of natural aging and heart failure. Echocardiography showed that both diastolic and systolic functions were partially rescued. The UW group, which had tested many other molecules, noted that urolithin A had the broadest effect across multiple heart function parameters. In human studies, the 'Energize' trial gave 1,000 mg to sedentary older adults for 4 months and saw significant improvements in muscle endurance and strength, along with reductions in CRP and inflammatory cytokines. A retrospective analysis of that trial found that ceramides, a new heart disease risk biomarker, were significantly lowered. David emphasized that while these results are promising, they are not a substitute for a healthy lifestyle but an add-on. The 1 g dose is the most efficient based on their data. He also shared that he personally cannot produce urolithin A from pomegranate juice due to his gut microbiome, highlighting the need for direct supplementation.

David explained that ceramides accumulate with aging, diabetes, and obesity, and their elevation in blood is a proven risk factor for heart disease. In the Energize trial, even healthy older adults had ceramide levels above the healthy threshold, and urolithin A significantly reduced them. This suggests that ceramide testing could be used to identify individuals who might benefit from mitochondrial support and to monitor the effectiveness of interventions. The test is becoming more accessible, with Mayo Clinic already offering it and Quest likely to follow.

The team took leftover blood samples from the 'Energize' trial, where sedentary older adults received 1,000 mg of urolithin A or placebo for 4 months. They measured ceramides and found that even in these healthy elderly, some ceramide levels were above the healthy threshold, indicating they were on a trajectory toward higher risk. Urolithin A significantly decreased several of these ceramide species. This is particularly exciting because it provides a direct biomarker link between mitochondrial health and cardiovascular risk, without needing echocardiography. David emphasized that this is preliminary but promising, and they plan to design proper clinical trials with heart function endpoints. The ceramide panel is currently available through Mayo Clinic and potentially Quest, making it accessible for clinicians to monitor interventions.

In collaboration with Louise Burke at Australian Catholic University, semi-professional and professional runners underwent a training camp with downhill running, an eccentric exercise that causes significant muscle damage. Those taking urolithin A showed a mild improvement in performance—small but potentially decisive at elite levels, likened to the difference between silver and gold. More importantly, blood markers of muscle damage and inflammation were reduced, indicating faster recovery. This suggests that urolithin A could help athletes train more efficiently and recover quicker, possibly by enhancing mitochondrial quality control in muscle. The full results are pending publication.