Accelerated Kidney Aging in Diabetes Mellitus.

Area of Science:

• Nephrology
• Gerontology
• Endocrinology

Background:

• Kidney structure and function decline with age, a process accelerated in diabetes mellitus (DM).
• Diabetic kidney aging involves stresses like advanced glycation end products (AGEs), hypertension, oxidative stress, and inflammation.
• Hallmarks include cellular senescence markers and a pro-inflammatory secretory phenotype.

Purpose of the Study:

• To review the mechanisms of accelerated kidney aging in diabetes.
• To discuss the role of cellular senescence, autophagy, and key proteins (Klotho, Sirt1) in diabetic nephropathy (DN).
• To explore potential therapeutic interventions for aging-related DN.

Main Methods:

• Literature review of studies on kidney aging, diabetes, cellular senescence, and autophagy.
• Analysis of the interplay between AGEs, oxidative stress, inflammation, and cellular aging pathways in diabetic kidneys.
• Evaluation of current and potential therapeutic strategies for DN.

Main Results:

• Accelerated kidney aging in DM is linked to cellular senescence, telomere shortening, and a specific secretory phenotype.
• Lysosome-dependent autophagy and antiaging proteins Klotho and Sirt1 are crucial, with autophagy acting as a convergent pathway.
• Metformin and SGLT2 inhibitors show promise for their antiaging effects beyond glucose control.

Conclusions:

• The autophagy-lysosome system is a central mechanism in diabetic kidney aging.
• Targeting Klotho, Sirt1, and autophagy pathways offers potential for novel DN therapies.
• Further research is needed on the long-term benefits of interventions like diet and specific drugs.