Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

Calvo‐Rubio, Miguel; Burón, Ma Isabel; López‐Lluch, Guillermo; Navas, Plácido; Cabo, Rafael de; Ramsey, Jon J.; Villalba, José M.; González‐Reyes, José A.

doi:10.1111/acel.12451

Cited by 24 publications

(16 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The age-related changes in the kidney can also be modulated by caloric restriction. In calorie-restricted animals, age-associated structural and functional changes in the kidney were mitigated and animals were resistant to diverse experimental kidney injuries ( Calvo-Rubio et al, 2016 ). In humans, life-long caloric restriction is not feasible, but the beneficial effects of even short-term calorie restriction have been unequivocally demonstrated, including reduced blood pressure, body weight, blood cholesterol, blood glucose, and attenuated atherosclerosis, as well as a decrease in blood urea nitrogen, creatinine, and uric acid ( Walford et al, 2002 ).…”

Section: Therapeutic Strategies For Renal Ageingmentioning

confidence: 99%

The ageing kidney: Molecular mechanisms and clinical implications

Fang

Gong

Haller

et al. 2020

Ageing Research Reviews

109

View full text Add to dashboard Cite

As human life expectancy keeps increasing, ageing populations present a growing challenge for clinical practices. Human ageing is associated with molecular, structural, and functional changes in a variety of organ systems, including the kidney. During the ageing process, the kidney experiences progressive functional decline as well as macroscopic and microscopic histological alterations, which are accentuated by systemic comorbidities like hypertension and diabetes mellitus, or by preexisting or underlying kidney diseases. Although ageing per se does not cause kidney injury, physiologic changes associated with normal ageing processes are likely to impair the reparative capacity of the kidney and thus predispose older people to acute kidney disease, chronic kidney disease and other renal diseases. Mechanistically, cell senescence plays a key role in renal ageing, involving a number of cellular signaling mechanisms, many of which may be harnessed as interventional targets for slowing or even reversing kidney ageing. This review summarizes the clinical characteristics of renal ageing, highlights the latest progresses in deciphering the role of cell senescence in renal ageing, and envisages potential interventional strategies and novel therapeutic targets for preventing or improving renal ageing in the hope of maintaining long-term kidney health and function across the life course.

show abstract

Section: Therapeutic Strategies For Renal Ageingmentioning

confidence: 99%

The ageing kidney: Molecular mechanisms and clinical implications

Fang

Gong

Haller

et al. 2020

Ageing Research Reviews

109

View full text Add to dashboard Cite

show abstract

“…78,80,81 For the kidney, it has been shown that calorie restriction counteracts basically all age-associated changes including glomerulosclerosis, tubular atrophy, and interstitial fibrosis. 9,34,[82][83][84] In addition to examination of its role in calorie restriction, autophagy has been intensively studied in aging and in different disease models in the kidney. 85 It was suggested that because of their longevity, podocytes, as well as tubular cells, might be particularly dependent on autophagy for effective "self-cleaning" from protein aggregates and defective organelles during the lifespan.…”

Section: Structural and Functional Changes Of Kidney Cellsmentioning

confidence: 99%

“…In this review, we have introduced the renal benefits of calorie restriction. 9,34,[82][83][84]131 However, long-term calorie restriction with optimal nutrition is very difficult to achieve and unlikely to become clinically relevant in the near future. Several nutritional factors and small compounds mimicking the calorie restriction effects by regulating nutrient sensing pathways or by inducing autophagy are in different phases of preclinical and clinical testing.…”

Section: Therapeutic Potentialmentioning

confidence: 99%

Molecular mechanisms of renal aging

Schmitt

Melk

2017

Kidney International

175

143

View full text Add to dashboard Cite

Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of acute kidney injury and chronic kidney disease. The aging kidney undergoes complex changes that predispose to renal pathology. The underlying molecular mechanisms could be the target of therapeutic strategies in the future. Here, we summarize recent insight into cellular and molecular processes that have been shown to contribute to the renal aging phenotype.The main clinical finding of renal aging is the decrease in glomerular filtration rate, and its structural correlate is the loss of functioning nephrons. Mechanistically, this has been linked to different processes, such as podocyte hypertrophy, glomerulosclerosis, tubular atrophy, and gradual microvascular rarefaction. Renal functional recovery after an episode of acute kidney injury is significantly worse in elderly patients. This decreased regenerative potential, which is a hallmark of the aging process, may be caused by cellular senescence. Accumulation of senescent cells could explain insufficient repair and functional loss, a view that has been strengthened by recent studies showing that removal of senescent cells results in attenuation of renal aging. Other potential mechanisms are alterations in autophagy as an important component of a disturbed renal stress response and functional differences in the inflammatory system. Promising therapeutic measures to counteract these age-related problems include mimetics of caloric restriction, pharmacologic renin-angiotensin-aldosterone system inhibition, and novel strategies of senotherapy with the goal of reducing the number of senescent cells to decrease aging-related disease in the kidney.

show abstract

“…For example, kidney aging indicators such as glomerular enlargement, podocyte hypertrophy, and mitochondrial abnormality have been delayed or even reversed by CR [ 7 , 8 ]. Similarly, other researchers have shown that CR attenuates most of the analyzed age-related markers in kidney, such as glomerular basement membrane (GBM) thickness, mitochondrial mass in complex proximal tubules and autophagic markers in aged kidney [ 9 ]. Furthermore, CR has been shown to decrease age-associated renal fibrosis and chronic kidney diseases [ 10 ].…”

Section: Introductionmentioning

confidence: 98%

MMP2-A2M interaction increases ECM accumulation in aged rat kidney and its modulation by calorie restriction

et al. 2017

View full text Add to dashboard Cite

Age-associated renal fibrosis is related with renal function decline during aging. Imbalance between accumulation and degradation of extracellular matrix is key feature of fibrosis. In this study, RNA-sequencing (RNA-Seq) results based on next-generation sequencing (NGS) data were analyzed to identify key proteins that change during aging and calorie restriction (CR). Among the changed genes, A2M and MMP2, which are known to interact, exhibited the highest between centrality (BC) and degree values when analyzed by protein–protein interaction (PPI). Both mRNA and protein levels of MMP2 and A2M were increased during aging. Furthermore, the interaction between MMP2 and A2M was verified by immunoprecipitation and immunohistochemistry. MMP2 activity was further measured under the presence or absence of A2M-MMP2 interaction. MMP2 activity, which was increased under the absence of A2M-MMP2 interaction, was significantly decreased under the presence of interactions in aged kidney. We further hypothesized that the interaction between A2M-MMP2 played a role in the inactivation of MMP2 leading to accumulation of ECM including collagen type I and IV. Aged kidney showed highly accumulated MMP2 substrate proteins despite of increased MMP2 protein expression and CR blunted these accumulation. Additional in vivo analysis revealed that the signal transducer and activator of transcription (STAT) 3 transcriptional factor was significantly increased thus increasing A2M expression during aging. STAT3 activating cytokines were also highly increased in aged kidney. In conclusion, the results of the present study indicate that A2M-MMP2 interaction has a role in age-associated renal ECM accumulation and in the suppression such fibrosis by CR.

show abstract

Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice

Cited by 24 publications

References 43 publications

The ageing kidney: Molecular mechanisms and clinical implications

The ageing kidney: Molecular mechanisms and clinical implications

Molecular mechanisms of renal aging

MMP2-A2M interaction increases ECM accumulation in aged rat kidney and its modulation by calorie restriction

Contact Info

Product

Resources

About