{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:29:14Z","timestamp":1785432554706,"version":"3.56.0"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004846","name":"Beijing University of Chinese Medicine","doi-asserted-by":"crossref","award":["90020371720023"],"award-info":[{"award-number":["90020371720023"]}],"id":[{"id":"10.13039\/501100004846","id-type":"DOI","asserted-by":"crossref"}]},{"award":["90020371720023"],"award-info":[{"award-number":["90020371720023"]}],"id":[{"id":"https:\/\/ror.org\/05damtm70","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82574621"],"award-info":[{"award-number":["82574621"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82574621"],"award-info":[{"award-number":["82574621"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>We investigated whether pyrroloquinoline quinone (PQQ) could improve cognitive performance in twenty-month-old naturally aged mice and explored the potential mechanisms involved. Results showed that PQQ supplementation improved spatial working memory and recognition memory without inducing anxiety-like behavior, and was associated with better preservation of hippocampal neuronal integrity. In HT-22 hippocampal neuronal cells, PQQ reduced reactive oxygen species (ROS) accumulation, restored mitochondrial membrane potential, and enhanced mitochondrial respiratory capacity. Hippocampal transcriptomic analysis and upstream regulator prediction identified sirtuin 1 (SIRT1) as a major regulator associated with the PQQ-induced transcriptional response, while uncoupling protein 2 (UCP2) emerged as a candidate downstream mitochondrial effector. Consistently, PQQ increased hippocampal SIRT1 protein expression and downregulated UCP2 at both mRNA and protein levels. Pharmacological inhibition of SIRT1 attenuated the PQQ-induced increase in ATP production and partially weakened the regulatory effect of PQQ on UCP2, supporting the involvement of SIRT1 in PQQ-associated mitochondrial bioenergetic regulation. Collectively, these findings indicate that PQQ improves cognitive-related behavioral performance in naturally aged mice and is associated with mitochondrial bioenergetic regulation, and suggest that modulation of a SIRT1\u2013UCP2-associated pathway may contribute to its neuroprotective effects.<\/jats:p>","DOI":"10.3390\/antiox15080921","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:53:26Z","timestamp":1784901206000},"page":"921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyrroloquinoline Quinone Improves Cognitive-Related Behavioral Performance Associated with Enhanced Mitochondrial Bioenergetics in Naturally Aged Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Yun","family":"Yan","sequence":"first","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3339-9225","authenticated-orcid":false,"given":"Di","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7228-8763","authenticated-orcid":false,"given":"Chunxia","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiutang","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoliang","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanhua","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Li","sequence":"additional","affiliation":[{"name":"Shenzhen Maternity and Child Healthcare Hospital, Women and Children\u2019s Medical Center, Southern Medical University, Shenzhen 518000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-8387","authenticated-orcid":false,"given":"Tao","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.4103\/NRR.NRR-D-24-01571","article-title":"Synaptic mitochondria in aging and neurodegenerative diseases: Functional decline and vulnerability","volume":"21","author":"Cicali","year":"2025","journal-title":"Neural Regen. 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