Research Paper Volume 12, Issue 17 pp 16852—16866
Spermidine inhibits neurodegeneration and delays aging via the PINK1-PDR1-dependent mitophagy pathway in C. elegans
- 1 Central Laboratory of The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China
- 2 Department of Toxicology, Zhejiang University School of Medicine, Hangzhou, China
- 3 Wenzhou Center for Disease Control and Prevention, Wenzhou, China
- 4 Department of Clinical Molecular Biology, University of Oslo, Oslo, Norway
- 5 Department of Toxicology, Hangzhou Normal University School of Medicine, Hangzhou, China
Received: April 2, 2020 Accepted: June 15, 2020 Published: September 9, 2020https://doi.org/10.18632/aging.103578
How to Cite
Copyright: © 2020 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Aging is the primary driver of various diseases, including common neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Currently there is no cure for AD and PD, and the development of novel drug candidates is demanding. Spermidine is a small anti-aging molecule with elimination of damaged mitochondria via the process of mitophagy identified as a molecular mechanism of action. Here, we show that spermidine inhibits memory loss in AD worms and improves behavioral performance, e.g., locomotor capacity, in a PD worm model, both via the PINK1-PDR1-dependent mitophagy pathway. Additionally, spermidine delays accelerated aging and improves healthspan in the DNA repair-deficient premature aging Werner syndrome (WS) worm model. While possible intertwined interactions between mitophagy/autophagy induction and DNA repair by spermidine are to be determined, our data support further translation of spermidine as a possible therapeutic intervention for such diseases.