Accelerated Kidney Aging in Diabetes Mellitus

Figure 3

Klotho, Sirt1, and lysosome-dependent autophagy in DN. Under physiological conditions, the antiaging protein klotho and Sirt1 can enhance basal autophagy, protecting the kidney from DN and aging. Under DM conditions, the expression of Klotho and Sirt1 in the kidney is downregulated. Besides, the autophagy is not able to maintain cellular homeostasis and resist renal cell senescence. This overwhelmed suppression in DN accelerates kidney aging. The solid lines with black arrowheads indicate promoting function. The solid lines with black truncated ends stand for inhibiting function. The dotted lines in black show the disturbed and altered regulatory function in the diabetic kidney with aging. The solid line in green represents autophagy from normal to dysfunction. Abbreviations: DDR: DNA damage response; SASP: senescence-associated secretory phenotype; ROS: reactive oxygen species; ATM: ataxia telangiectasia mutated; MAPK: mitogen-activated protein kinase; ERK: extracellular signal-regulated kinase; NF-κB: nuclear factor-kappa B; Nrf2: nuclear factor E2-related factor 2; SIRT1: sirtuin 1; AMPK: adenosine monophosphate–activated protein kinase; mTOR: mammalian target of rapamycin; LC3: microtubule-associated protein 1A/1B–light chain 3; Atg5: autophagy-related 5; Atg7: autophagy-related 7; BCL2: B-cell lymphoma 2; P62: SQSTM1/sequestosome 1; FOXO3a: forkhead box O3a; FOXO4: forkhead box O4; TGF-β: transforming growth factor-β; LMP: lysosomal membrane permeabilization.

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