{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:09:30Z","timestamp":1790298570841,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010AG076490"],"award-info":[{"award-number":["R01\u2010AG076490"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>L\u2010Kynurenine (L\u2010Kyn), a product of tryptophan catabolism, increases with age and has been associated with reduced physical function and increased frailty in humans. Robustly expressed in skeletal muscle, kynurenine aminotransferases (KATs) degrade L\u2010Kyn into kynurenic acid and are regulated by the transcriptional co\u2010regulator peroxisome proliferator\u2013activated receptor gamma coactivator 1\u2010alpha (PGC1\u03b1).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The study investigated (1) if elevating L\u2010Kyn levels via a diet intervention exacerbates an age\u2010related decline in physical, muscle and mitochondrial functions and (2) if transgenic expression of PGC1\u03b1 in skeletal muscle (MCK\u2010PGC1\u03b1) protects against age\u2010dependent L\u2010Kyn associated pathology in a cohort of aging MCK\u2010PGC1\u03b1 transgenic mice and their wildtype littermates of both sexes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009262). Physical function was assessed longitudinally from 16 to 24\u2009months of age using treadmill endurance capacity, grip strength, walking speed and daily physical activity. Muscle function was assessed in\u00a0situ using nerve\u2010mediated contraction of the soleus muscle. Mitochondrial energetics were assessed using high resolution respirometry and fluorescence spectroscopy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MCK\u2010PGC1\u03b1 transgenic mice had significantly higher KAT expression ~2\u20135\u2010fold compared with wildtype littermates (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001 for all isoforms). A main effect of L\u2010Kyn diet was observed for decreasing treadmill endurance capacity and daily physical activity in male mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2266\u20090.002). A main effect of L\u2010Kyn diet for decreasing maximal walking speed only was found in female mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.037). Correspondingly, L\u2010Kyn increased frailty prevalence in male (+17%) and female (+26%) wildtype mice (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025 and 0.0001 respectively), which was mitigated by MCK\u2010PGC1\u03b1 in both sexes. Soleus muscle strength and power were not impacted by diet or genotype in either sex (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.5). Mitochondrial oxidative phosphorylation function in male and female MCK\u2010PGC1\u03b1 mice was greater than wild type mice regardless of diet (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.04), which is likely driven by upregulated expression of mitochondrial biogenesis related genes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We conclude that PGC1\u03b1 overexpression in skeletal muscle mitigates the exacerbation of physical frailty induced by elevated circulating L\u2010Kyn in aging mice, in part through increased skeletal muscle capacity for L\u2010Kyn metabolism due to PGC1\u03b1\u2010induced increase in muscle KAT expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70214","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T08:40:22Z","timestamp":1770021622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Elevating Circulating L\u2010Kynurenine Promotes Frailty in Aging Mice"],"prefix":"10.1002","volume":"17","author":[{"given":"Mia\u00a0Y.","family":"Kawaida","sequence":"first","affiliation":[{"name":"Department of Applied Physiology and Kinesiology The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail\u00a0L.","family":"Tice","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob\u00a0A.","family":"Lackey","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Izaguirre","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Wei\u2010LaPierre","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology The University of Florida  Gainesville Florida USA"},{"name":"Center for Exercise Science The University of Florida  Gainesville Florida USA"},{"name":"Myology Institute The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell\u00a0T.","family":"Hepple","sequence":"additional","affiliation":[{"name":"Myology Institute The University of Florida  Gainesville Florida USA"},{"name":"Department of Physical Therapy The University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-029X","authenticated-orcid":false,"given":"Terence\u00a0E.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology The University of Florida  Gainesville Florida USA"},{"name":"Center for Exercise Science The University of Florida  Gainesville Florida USA"},{"name":"Myology Institute The 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