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SIRT3-dependent mitochondrial redox homeostasis protects against age-related tendon degeneration.

Created on 09 Sep 2026

Authors

Yiqiong Nie, Jiefu Zhou, Xueying Zhang, Yang Chen, Tao Zhang, Wei Peng, Linfeng Wang, Shouan Zhu, Hongbin Lu

Published in

Bone & joint research. Volume 15. Issue 9. Pages 1123-1135. Sep 09, 2026. Epub Sep 09, 2026.

Abstract

Mitochondrial redox homeostasis is closely linked to the ageing processes of tendons, whether in normal or pathological conditions. This study employed an innovative approach to examine the role of sirtuin 3 (SIRT3) in mitochondrial dysfunction in the aged murine supraspinatus tendon (ST).
Pathological changes and collagen organization in tendons, along with variations in SIRT3 levels and oxidative stress, were initially assessed in mice of different ages. In vitro experiments were then performed to evaluate the effects of oxidative senescence on tendon cells, including cellular activity, phenotype, and collagen secretion. Finally, we explored the underlying mechanisms via which SIRT3 regulates mitochondrial redox homeostasis.
Histological and immunofluorescence analyses revealed a decline in SIRT3 levels within tenocytes as ageing progressed, accompanied by mitochondrial dysfunction and ageing-related phenotypes. The reduction in SIRT3 with age led to an increase in reactive oxygen species levels in tendon cells. However, enhancing SIRT3 expression in cells under oxidative stress was found to activate the SOD2 and Keap1/Nrf2/HO-1 signalling pathways, effectively reversing cellular senescence.
SIRT3 plays a pivotal role in maintaining mitochondrial redox homeostasis in ST by regulating the mitochondrial antioxidant network to mitigate ageing and oxidative stress in tendon cells. Targeting SIRT3 in ST degeneration may offer a promising therapeutic approach.

PMID:
42710873
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

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