Authors
Tengfei Liang, Lixia Wang, Shujuan Kang, Xiaoyan Pang, Hexin Yan
Published in
The journals of gerontology. Series A, Biological sciences and medical sciences. Sep 25, 2026. Epub Sep 25, 2026.
Abstract
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 eight 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-α, and IL-1β; enhanced Mn-SOD and CAT activities; increased GSH and ATP levels and mitochondrial content; and upregulated PGC-1α/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-1α, suggesting that the Alda-1-induced upregulation of PGC-1α 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-1α signaling pathway.
PMID:
42789758
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.
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