Dynamic force sensing by bone delays aging and extends lifespan.

Zhimin Zhang, Zhiqing Cai, Shencai Liu, Yun Chu, Zhengtao Jiang, Wuju Zhang, Yating Pan, Ying Lin, Xiaocui Wei, Jingting Chen, Junnan Huangfu, Bocheng Nan, Yibo Zhou, Le Hu, Wenquan Liang, Zhipeng Zou, Minjun Huang, Sheng Lu, Di Lu, Xiaochun Bai

Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, Guangdong, China; State Key Laboratory of Multi-organ Injury Prevention and Treatment, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, Guangdong, China. · pubmed

Paper

Abstract

Physical activity promotes health primarily by decelerating the aging process. Bone is one of the tissues capable of sensing mechanical force and can adapt to different physical demands. However, its role in whole-body aging is unknown. We found that reduced mechano-sensing in osteocytes, caused by deletion of the mechanosensory channel, Piezo1, accelerated whole-body aging in mice. Dynamic tibial axial loading (DTAL) in mice at 20-24 months of age extended both healthspan and lifespan (9.4%/79.5 days). Furthermore, DTAL reversed bone marrow immunosenescence and induced anti-aging and protective factors while downregulating pro-aging and pro-inflammatory factors. We also identified pigment epithelium-derived factor (PEDF) as a novel mechano-responsive anti-aging factor that is highly associated with healthy aging in humans. Thus, our findings highlighted an essential role for bone mechano-sensing in whole-body aging. This could potentially be manipulated to prevent aging, extend health, and aid those unable to exercise or with decreased mobility.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

Deletion of the mechanosensory channel Piezo1 in osteocytes accelerates whole-body aging, while dynamic tibial loading extends lifespan and healthspan by inducing anti-aging factors like PEDF. This is highly relevant because it identifies a specific, non-exercise-dependent mechanism (bone mechano-sensing) that regulates systemic aging, offering a potential therapeutic target for individuals who cannot exercise.

Author of this paper? Send a correction.