Pyrroloquinoline Quinone Improves Cognitive-Related Behavioral Performance Associated with Enhanced Mitochondrial Bioenergetics in Naturally Aged Mice.

Overview

Authors: Yun Yan¹, Di Deng¹, Chunxia Tan¹, Qi Lu¹, Jiutang Sun¹, Shaoliang Wu¹, Zhanhua Jiang¹, Yibo Li², Tao Lu¹

School of Life Sciences, Beijing University of Chinese Medicine, Beijing 102488, China; (Y.Y.); (D.D.); (C.T.); (Q.L.); (J.S.); (S.W.); (Z.J.)
Shenzhen Maternity and Child Healthcare Hospital, Women and Children’s Medical Center, Southern Medical University, Shenzhen 518000, China

Institutions: Beijing University of Chinese Medicine (China); Shenzhen Maternity and Child Healthcare Hospital (China); Southern Medical University (China)

Journal: Antioxidants (Basel, Switzerland), volume 15, issue 8, article 921

Dates: received 20 May 2026; accepted 17 July 2026; published online 24 July 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.3390/antiox15080921 · PMID 42650185 · PMCID PMC13509254 · OpenAlex W7170327135

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: mouse (organism), cellular / molecular (subfield)

Methods: Statistics, Preprocessing

Keywords: pyrroloquinoline quinone, natural aging, cognitive decline, mitochondria function, oxidative stress

Topic: Microbial metabolism and enzyme function (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: National Natural Science Foundation of China (82574621); Beijing University of Chinese Medicine (90020371720023)

Citations: not cited yet (Europe PMC); 47 references in the paper

Abstract

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–UCP2-associated pathway may contribute to its neuroprotective effects.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

Datasets cited

geo:GSE338219, at NCBI GEO; found in “Data Availability Statement”

Data Availability Statement

The RNA sequencing data generated in this study have been deposited in the Gene Expression Omnibus (GEO) database under accession number GSE338219 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE338219). Other data supporting the findings of this study are included in the article and Supplementary Materials.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 2, 28 September 2026

Funding: added National Natural Science Foundation of China: 82574621; Beijing University of Chinese Medicine: 90020371720023

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 5 keywords, 47 references.

Cite

This paper

Yan, Y., Deng, D., Tan, C., Lu, Q., Sun, J., Wu, S., Jiang, Z., Li, Y., & Lu, T. (2026). Pyrroloquinoline Quinone Improves Cognitive-Related Behavioral Performance Associated with Enhanced Mitochondrial Bioenergetics in Naturally Aged Mice. Antioxidants (Basel, Switzerland), 15(8), 921. https://doi.org/10.3390/antiox15080921

BibTeX

@article{yan2026pyrroloquinoline, author = {Yan, Yun and Deng, Di and Tan, Chunxia and Lu, Qi and Sun, Jiutang and Wu, Shaoliang and Jiang, Zhanhua and Li, Yibo and Lu, Tao}, title = {{Pyrroloquinoline Quinone Improves Cognitive-Related Behavioral Performance Associated with Enhanced Mitochondrial Bioenergetics in Naturally Aged Mice}}, journal = {Antioxidants (Basel, Switzerland)}, year = {2026}, month = jul, volume = {15}, number = {8}, pages = {921}, publisher = {Multidisciplinary Digital Publishing Institute (MDPI)}, issn = {2076-3921}, doi = {10.3390/antiox15080921}, url = {https://doi.org/10.3390/antiox15080921}, pmid = {42650185}, pmcid = {PMC13509254} }

RIS

TY - JOUR AU - Yan, Yun AU - Deng, Di AU - Tan, Chunxia AU - Lu, Qi AU - Sun, Jiutang AU - Wu, Shaoliang AU - Jiang, Zhanhua AU - Li, Yibo AU - Lu, Tao TI - Pyrroloquinoline Quinone Improves Cognitive-Related Behavioral Performance Associated with Enhanced Mitochondrial Bioenergetics in Naturally Aged Mice T2 - Antioxidants (Basel, Switzerland) J2 - Antioxidants (Basel) PY - 2026 DA - 2026/07/24 VL - 15 IS - 8 SP - 921 SN - 2076-3921 PB - Multidisciplinary Digital Publishing Institute (MDPI) DO - 10.3390/antiox15080921 UR - https://doi.org/10.3390/antiox15080921 LA - en ER -

CSL-JSON

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