Intermittent fasting mitigates kidney fibrosis following ischemia-reperfusion injury by suppressing cellular senescence

Sep 12, 2025Biochemical and biophysical research communications

Intermittent fasting may reduce kidney scarring after blood flow injury by slowing cell aging

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Abstract

Intermittent fasting (IF) significantly reduced renal fibrosis in a murine model of acute kidney injury (AKI).

Mice subjected to ischemia-reperfusion injury (IRI) exhibited pronounced tubulointerstitial fibrosis two months post-surgery.
Fibrosis levels were markedly lower in mice receiving intermittent fasting compared to those that did not.
IF reduced protein expression of p21 and downregulated key senescence markers Cdkn1a and Cdkn2a.
The expression of senescence-associated secretory phenotype (SASP) cytokines was suppressed in the IF group.
IF restored levels of major metabolic regulators linked to energy homeostasis, including SIRT1, phosphorylated AMPK, and PGC-1α.

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Cellular senescence is recognized as a key mechanism contributing to maladaptive renal recovery and the development of fibrosis after acute kidney injury (AKI). Intermittent fasting (IF), a non-pharmacological dietary strategy, influences aging pathways and tissue homeostasis; however, its contribution to kidney fibrosis is still not well characterized. This study aimed to evaluate how IF influences renal fibrosis and cellular senescence using a murine model of AKI resulting from ischemia-reperfusion injury (IRI). Male C57BL/6 mice underwent unilateral IRI, followed by assignment of the IF group to a 5:2 schedule incorporating two 24-h fasts each week for eight weeks. Animals were divided into four groups: sham, IF, IRI, and IF + IRI. Two months after surgery, the IRI group developed pronounced tubulointerstitial fibrosis, while fibrosis was markedly attenuated in the IF + IRI group. Molecular analyses revealed that IF reduced protein expression of p21 and downregulated Cdkn1a and Cdkn2a transcripts, two key senescence markers. Furthermore, IF suppressed the expression of senescence-associated secretory phenotype (SASP) cytokines, including TNF-α, TGF-β, IL-6, IL-1α, and IL-1β. In parallel, IF restored the expression of major metabolic regulators related to energy homeostasis, such as SIRT1, phosphorylated AMPK, and PGC-1α. Collectively, these findings demonstrate that IF confers protection against renal fibrosis after IRI-induced AKI, and suggest that its beneficial effects may be mediated, at least in part, through the inhibition of cellular senescence and the enhancement of metabolic resilience.

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Intermittent fasting mitigates kidney fibrosis following ischemia-reperfusion injury by suppressing cellular senescence

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