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Here, we combined Tat-Beclin1, an autophagy agonist, and endurance training to determine whether Tat-Beclin1 enhances exercise adaptation in old male mice. Tat-Beclin1 was administered intraperitoneally (TB group, 15 mg\/kg, 2x\/week) as a standalone therapy, or in combination with endurance training (TB+Exe group, 70% of maximal running speed 3x\/week) for 1 month in 23-month-old male C57BL\/6J mice. Control groups were age-matched cage controls and exercise-only groups. Animals were assessed for grip strength, endurance capacity on a treadmill, and balance and coordination on a rotarod. Gastrocnemius\/plantaris (G\/P) and tibialis anterior muscles were harvested for western blotting, myofiber typing, and proteomic profiling (G\/P only). TB+Exe led to significant increases in grip strength, endurance capacity, and balance and coordination performance beyond those observed in the TB and Exe groups alone. Autophagy markers, including Beclin1, the LC3B-II\/I ratio, and p62, did not differ among groups. A proteomic analysis of the G\/P muscle revealed that TB upregulated biological processes involved in muscle contraction and adaptation, whereas TB+Exe increased mitochondrial bioenergetic processes and, surprisingly, upregulated acute inflammatory responses, including proteins such as haptoglobin and orosomucoid-1. We conclude that combining Tat-Beclin1 and endurance training may represent a new approach to attenuate aging-related decline in physical function.<\/jats:p>\n                <jats:sec>\n                  <jats:title>New &amp; Noteworthy<\/jats:title>\n                  <jats:p>We show evidence that combining Tat-Beclin1 and endurance training (TB+Exe) resulted in greater improvements in physical function in 24-month-old male mice than either standalone therapy. We also show that TB+Exe upregulates traditional exercise-like biological processes and unexpectedly upregulates acute-inflammatory proteins (e.g., orosomucoid-1), which are thought to improve physical function in preclinical studies. Our study suggests that TB may be a new drug enhancing physical function, especially when combined with endurance training in old male mice.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.07.723527","type":"posted-content","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T21:40:13Z","timestamp":1778622013000},"source":"Crossref","is-referenced-by-count":0,"title":["Short-Term Combined Tat-Beclin1 and Endurance Training Improves Age-Related Decline in Physical Function in Male Mice"],"prefix":"10.64898","author":[{"given":"Thuan Thien","family":"Tchen","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA"},{"name":"School of Translational Biomedical Engineering and Sciences (TBES), Rowan University, Stratford, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakibur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6373-5213","authenticated-orcid":false,"given":"Thaysa","family":"Ghiarone","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9640-9158","authenticated-orcid":false,"given":"Lynn A.","family":"Spruce","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein","family":"Fazelina","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Department of Biomedical and Health Informatics, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Brown","sequence":"additional","affiliation":[{"name":"Proteomics Core Facility, Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charalampos","family":"Papachristou","sequence":"additional","affiliation":[{"name":"Department of Mathematics, Rowan University, Glassboro, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5742-9145","authenticated-orcid":false,"given":"Sue C.","family":"Bodine","sequence":"additional","affiliation":[{"name":"Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3162-3804","authenticated-orcid":false,"given":"Vitor A.","family":"Lira","sequence":"additional","affiliation":[{"name":"Department of Health, Sport, and Human Physiology, Fraternal Order of Eagles Diabetes Research Center, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8230-0012","authenticated-orcid":false,"given":"Kleiton A. 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