Advances in translational research最新文献

{"title":"Ovarian-derived signals reprogram hepatic lipid metabolism in aging: Implications for therapeutic targeting of metabolic dysfunction.","authors":"Nathan D McCoy, Michael T Kinter, Augusto Schneider, Fabiola Santos, Michal M Masternak, Jeffrey B Mason","doi":"10.1556/1661.2026.00112","DOIUrl":"10.1556/1661.2026.00112","url":null,"abstract":"<p><strong>Background and aim: </strong>Aging in mammals is a complex, multifaceted process involving the progressive decline of physiological functions, in which energy metabolism plays a pivotal role. <i>β</i>-oxidation-the primary pathway for converting fatty acids into energy-is tightly linked to aging and to female reproductive senescence. In the present study, we investigated how ovarian tissue remodels hepatic proteins central to the <i>β</i>-oxidation pathway.</p><p><strong>Methods: </strong>Liver proteomes were analyzed in CBA/J control mice at 4, 13, 23, and 27 months of age and compared with those of 23-month-old mice that received transplants of young ovarian tissue at 13 months. <i>β</i>-oxidation proteins were quantified using high-resolution mass spectrometry. Serum triglycerides were measured enzymatically, and metabolic cage analyses were performed to assess substrate utilization and energy balance.</p><p><strong>Results: </strong>Ovarian tissue transplantation substantially modulates the expression of <i>β</i>-oxidation-related proteins and reduces systemic lipid accumulation in aged mice. These proteomic shifts are consistent with enhanced metabolic efficiency and decreased oxidative stress-mechanisms well-established as drivers of extended health span and longevity. Results apply to menopause dyslipidemia, insulin resistance, metabolic syndrome, NAFLD, and aging. Transplants reduce <i>β</i>-oxidation proteins and triglycerides, improving hepatic lipid clearance and steatosis risk. Identifying ovarian signals enables non-surgical mimics via peptides or modulators. Changes align with PPARα agonists, CPT1 modulators, mitochondria-targeted antioxidants (MitoQ), and NAD⁺/sirtuin pathways-offering testable routes to replicate ovarian benefits.</p><p><strong>Conclusions: </strong>Ovarian-derived signals induce metabolic reprogramming in aged mice, characterized by reduced <i>β</i>-oxidation protein expression, decreased triglyceride accumulation, and improved metabolic efficiency. These findings provide a molecular framework for understanding how ovarian-derived factors may govern metabolism and organismal health during aging, with potential implications for interventions targeting age-related metabolic decline.</p>","PeriodicalId":524096,"journal":{"name":"Advances in translational research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}