{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:05Z","timestamp":1792785905882,"version":"4.5.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Hebei University of Engineering Innovation Fund Project","award":["SJ2401002220"],"award-info":[{"award-number":["SJ2401002220"]}],"id":[{"id":"https:\/\/ror.org\/036h65h05","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in aging and age-related neurodegenerative diseases, the impact of ALDH2 on age-related cognitive deficits and its underlying mechanisms have not been fully elucidated. This study aimed to explore the effects of ALDH2 on cognitive deficits in D-galactose-induced aging mice and illustrate the potential molecular mechanisms. We treated D-galactose-induced aging mice with Alda-1 (a potent agonist of ALDH2) for 8 weeks and observed the alterations in behavior, levels of oxidative stress and neuroinflammation, mitochondrial function, and expression of mitochondrial biogenesis-related genes. The results revealed that Alda-1 alleviated neuropathological changes in the hippocampus and ameliorated cognitive deficits in D-galactose-induced aging mice. Administration of Alda-1 further reduced the levels of 4-HNE, MDA, 3-NT, IL-6, TNF-\u03b1, and IL-1\u03b2; enhanced Mn-SOD and CAT activities; increased GSH and ATP levels and mitochondrial content; and upregulated PGC-1\u03b1\/NRF-1\/TFAM expression in the hippocampus of D-galactose-induced aging mice. Moreover, in D-galactose-treated HT22 cells, we found that the SIRT1 inhibitor EX527 reversed the Alda-1-induced upregulation of PGC-1\u03b1, suggesting that the Alda-1-induced upregulation of PGC-1\u03b1 is associated with SIRT1 signaling. Collectively, Alda-1 ameliorated cognitive deficits in D-galactose-induced aging mice by reducing neuroinflammation, enhancing antioxidative capability, promoting mitochondrial biogenesis, and modulating the SIRT1\/PGC-1\u03b1 signaling pathway.<\/jats:p>","DOI":"10.1093\/gerona\/glag241","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:28:31Z","timestamp":1790335711000},"source":"Crossref","is-referenced-by-count":0,"title":["Alda-1 alleviates the cognitive deficits in D-galactose-induced aging mice by regulating oxidative stress, neuroinflammation, and mitochondrial biogenesis"],"prefix":"10.1093","volume":"81","author":[{"given":"Tengfei","family":"Liang","sequence":"first","affiliation":[{"name":"School of Medicine, Affiliated Hospital, Hebei University of Engineering , Handan,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Wang","sequence":"additional","affiliation":[{"name":"School of 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