TAT-Beclin-1 peptide and TFEB activator C1 restore autophagy, protecting aging kidneys from septic AKI.

Aging significantly increases the incidence and severity of sepsis-associated acute kidney injury (SA-AKI), a devastating condition with poorly understood molecular underpinnings in the elderly. While autophagy is recognized as a crucial intrinsic protective mechanism against AKI, its specific role and regulation within aging kidneys remain largely unclear. This knowledge gap hinders the development of targeted therapies for SA-AKI in vulnerable older populations, where current interventions often fall short.

Researchers investigated autophagy activation in aging kidneys during SA-AKI in mice models. In vitro, they treated senescent renal proximal tubular cells with lipopolysaccharide (LPS) to induce damage, then intervened with TAT-Beclin-1 peptide to activate autophagy. They used single-cell sequencing to identify age-related changes in autophagy-associated genes, focusing on TFEB. Further experiments involved TFEB overexpression in senescent cells and in vivo treatment of aging mice with curcumin analog C1 (a TFEB activator) to assess its impact on LPS-induced AKI.