Muscle atrophy and weakness are prevalent and debilitating conditions in dogs that cannot be reliably prevented or treated by current approaches. In non-canine species, the natural dietary compound ursolic acid inhibits molecular mechanisms of muscle atrophy, leading to improvements in muscle health. To begin to translate ursolic acid to canine health, we developed a novel ursolic acid dietary supplement for dogs and confirmed its safety and tolerability in dogs. We then conducted a randomized, placebo-controlled, proof-of-concept efficacy study in older beagles with age-related muscle atrophy, also known as sarcopenia. Animals received placebo or ursolic acid dietary supplements once a day for 60 days. To assess the study’s primary outcome, we biopsied the quadriceps muscle and quantified atrophy-associated mRNA expression. Additionally, to determine whether the molecular effects of ursolic acid might have functional correlates consistent with improvements in muscle health, we assessed secondary outcomes of exercise participation and T-maze performance. Importantly, in canine skeletal muscle, ursolic acid inhibited numerous mRNA expression changes that are known to promote muscle atrophy and weakness. Furthermore, ursolic acid significantly improved exercise participation and T-maze performance. These findings identify ursolic acid as a natural dietary compound that inhibits molecular mechanisms of muscle atrophy and improves functional performance in dogs.

Cellular senescence drives aging and age-related dysfunction across multiple tissues, including the brain. Through a high-content, senescent cell-based phenotypic screen of a small panel of natural products, we identified tomatidine, an aglycone of tomatine found in tomatoes, as a previously unrecognized senotherapeutic agent. In senescent human brain microvascular endothelial cells and fibroblasts, tomatidine selectively suppressed SASP expression without affecting p16 ^Ink4a or p21 ^Cip1 levels consistent with a senomorphic effect. In aged mice, tomatidine reduced frailty and improved motor coordination and cognitive performance. These functional benefits were accompanied by reduced senescence markers (p16 ^Ink4a , p21 ^Cip1 , and telomere-associated DNA damage foci) in liver, skin, and hippocampal neurons, along with decreased neuroinflammation and microglial activation. Tomatidine also diminished brain endothelial cell senescence while enhancing tight junction protein expression, suggesting preserved blood–brain barrier integrity. Together, these findings identify tomatidine as a promising senescence-targeting compound with beneficial effects in aged mice and support its further evaluation in mechanistic and translational studies.

Cancer-induced muscle wasting affects many people with cancer, reducing treatment tolerance and survival. We identified a natural dietary compound, ursolic acid, that attenuates muscle atrophy across five preclinical cancer models spanning pancreatic, colon, and lung cancer. Ursolic acid inhibits cancer-induced changes in muscle mRNA expression, preserves muscle strength, and remains protective during chemotherapy, without affecting food intake or tumor burden. These results identify ursolic acid as a promising, translatable dietary supplement for supportive cancer care.

Cats frequently lose mobility when they become older, ill, or injured, leading to additional impairments in health and quality of life. To help address this problem, a dietary supplement for cats containing ursolic acid was tested. Ursolic acid is a natural dietary compound that promotes muscle health and mobility in several non-feline species. A 60-day proof-of-concept efficacy study of ursolic acid dietary supplementation was conducted in older domestic shorthair cats with sarcopenia (age-related skeletal muscle atrophy). In feline skeletal muscle, 12 mg of ursolic acid per day generated beneficial changes in skeletal muscle mRNA expression, including repression of mRNAs that promote muscle atrophy and weakness and induction of mRNAs that promote muscle health. Furthermore, ursolic acid generated significant improvements in several important measures of feline mobility, including jumping, playing with toys, rising from a resting position, and transitioning from a standing position to a sitting or lying position. These findings identify ursolic acid supplementation as a new nutritional approach for promoting beneficial molecular and functional mobility outcomes in cats.