Abstract
With aging, the kidney undergoes inexorable and progressive changes in structural and functional performance. These aging-related alterations are more obvious and serious in diabetes mellitus (DM). Renal accelerated aging under DM conditions is associated with multiple stresses such as accumulation of advanced glycation end products (AGEs), hypertension, oxidative stress, and inflammation. The main hallmarks of cellular senescence in diabetic kidneys include cyclin-dependent kinase inhibitors, telomere shortening, and diabetic nephropathy-associated secretory phenotype. Lysosome-dependent autophagy and antiaging proteins Klotho and Sirt1 play a fundamental role in the accelerated aging of kidneys in DM, among which the autophagy-lysosome system is the convergent mechanism of the multiple antiaging pathways involved in renal aging under DM conditions. Metformin and the inhibitor of sodium–glucose cotransporter 2 are recommended due to their antiaging effects independent of antihyperglycemia, besides angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Additionally, diet intervention including low protein and low AGEs with antioxidants are suggested for patients with diabetic nephropathy (DN). However, their long-term benefits still need further study. Exploring the interactive relationships among antiaging protein Klotho, Sirt1, and autophagy-lysosome system may provide insight into better satisfying the urgent medical needs of elderly patients with aging-related DN.
Highlights
The increasing global morbidity of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has provoked research efforts to overcome the growing prevalence of diabetic nephropathy (DN), which has been a global catastrophe due to limited efficacy with existing therapies and serious financial burden [1,2,3]
Short-term caloric restriction was demonstrated to play a protective role against renal senescence via increasing autophagic activity and reducing oxidative stress [155], which may be related to the modulation of AMPK/mammalian target of rapamycin (mTOR) signaling [156], attenuating inflammatory process via downregulation of NF-κB [157], as well as the suppression of apoptosis [158]
These results imply that traditional Chinese medicine (TCM) appear to have potential advantages to protect renal function against kidney aging in DM in the future
Summary
The increasing global morbidity of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has provoked research efforts to overcome the growing prevalence of diabetic nephropathy (DN), which has been a global catastrophe due to limited efficacy with existing therapies and serious financial burden [1,2,3]. Both T2DM and CKD are aging-related diseases. Feasible histopathological patterns of individuals often imply the presence of other pathogenic factors, such as aging-related nephropathy, resulting in the complicated and difficult diagnosis and treatment of type 2 DN [8]. Under the double risk factors of high glucose and aging, it is hypothesized that renal aging plays a vital role in the development of DN. We will discuss current knowledge on renal aging-related mechanisms and potential therapeutic targets of DN
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