Aging cellJul 21, 2026

Lower Levels of a Cell Cleanup Regulator and Faulty Cell Recycling Linked to Older Kidneys' Vulnerability to Infection-Related Injury

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jul 22, 2026

Abstract

Defective autophagy activation in aging kidneys may increase susceptibility to sepsis-associated acute kidney injury (SA-AKI).

Aging kidneys showed impaired autophagy activation in response to sepsis-associated acute kidney injury in mouse models.
Activation of autophagy using TAT-Beclin-1 peptide reduced apoptosis and inflammation in aged kidney cells exposed to harmful substances.
Single-cell sequencing identified significant age-related changes in genes associated with autophagy in septic acute kidney injury.
Overexpression of the gene TFEB partially restored autophagic activity in aged kidney cells, offering protection against damage.
In vivo treatment with a curcumin analog (C1), which activates TFEB, improved autophagy and reduced injury in aging kidneys.

Simplified

Sepsis-associated acute kidney injury (SA-AKI) is a common and devastating disease that has a significantly higher incidence and greater severity in elderly patients, but the molecular basis underlying SA-AKI in the elderly is largely unknown. Recent studies have proved autophagy as an intrinsic protective mechanism against AKI; however, the role and regulation of autophagy in aging kidneys remain unclear. Here we demonstrate that defective autophagy activation in aging kidneys is a key to their susceptibility to SA-AKI. In our experiments, the ability of autophagy activation was impaired in aging kidneys in response to SA-AKI in mice. In vitro, activation of autophagy with TAT-Beclin-1 peptide mitigated lipopolysaccharide (LPS)-induced apoptosis and inflammation in senescent renal proximal tubular cells. Single-cell sequencing revealed significant age-related alterations in autophagy-associated genes in septic AKI, including TFEB. Overexpression of TFEB could partially restore autophagic activity in senescent renal tubular cells and protect them from LPS-induced damage. Moreover, in vivo treatment with the curcumin analog C1 (a TFEB activator) enhanced autophagic function in aging kidneys and reduced LPS-induced AKI. These results demonstrate the defective autophagy activation in aging kidneys, which contributes to the SA-AKI sensitivity and susceptibility in the elderly, suggesting a therapeutic strategy by enhancing autophagy.

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Lower Levels of a Cell Cleanup Regulator and Faulty Cell Recycling Linked to Older Kidneys' Vulnerability to Infection-Related Injury

Abstract

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