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Calorie Restriction Provides Kidney Ischemic Tolerance in Senescence-Accelerated OXYS Rats
Nadezda V Andrianova1, Ljubava D Zorova1,2, Irina B Pevzner1,2
1Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Abstract:
Kidney diseases belong to a group of pathologies, which are most common among elderly people. With age, even outwardly healthy organisms start to exhibit some age-related changes in the renal tissue, which reduce the filtration function of kidneys and increase the susceptibility to injury. The therapy of acute kidney injury (AKI) is aggravated by the absence of targeted pharmacotherapies thus yielding high mortality of patients with AKI. In this study, we analyzed the protective effects of calorie restriction (CR) against ischemic AKI in senescence-accelerated OXYS rats. We observed that CR afforded OXYS rats with significant nephroprotection. To uncover molecular mechanisms of CR beneficial effects, we assessed the levels of anti- and proapoptotic proteins of the Bcl-2 family, COX IV, GAPDH, and mitochondrial deacetylase SIRT-3, as well as alterations in total protein acetylation and carbonylation, mitochondrial dynamics (OPA1, Fis1, Drp1) and kidney regeneration pathways (PCNA, GDF11). The activation of autophagy and mitophagy was analyzed by LC3 II/LC3 I ratio, beclin-1, PINK-1, and total mitochondrial protein ubiquitination. Among all considered protective pathways, the improvement of mitochondrial functioning may be suggested as one of the possible mechanisms for beneficial effects of CR.
Insights
Calorie restriction (CR) protects against acute kidney injury (AKI) in aging rats. This study suggests improved mitochondrial function is a key mechanism behind CR
Area of Science:
- Gerontology
- Nephrology
- Molecular Biology
Background:
- Kidney diseases are prevalent in elderly individuals, with age-related renal tissue changes reducing filtration and increasing injury susceptibility.
- Acute kidney injury (AKI) therapy is challenged by a lack of targeted treatments, leading to high patient mortality.
- Senescence-accelerated OXYS rats model age-related kidney decline and AKI susceptibility.
Purpose of the Study:
- To investigate the protective effects of calorie restriction (CR) against ischemic AKI in a rat model of accelerated aging.
- To elucidate the molecular mechanisms underlying the nephroprotective benefits of CR.
- To assess CR's impact on mitochondrial function, apoptosis, autophagy, and kidney regeneration pathways.
Main Methods:
- Senescence-accelerated OXYS rats were subjected to ischemic AKI, with some receiving calorie restriction (CR).
- Analysis of Bcl-2 family proteins, COX IV, GAPDH, SIRT-3, protein acetylation/carbonylation, and mitochondrial dynamics (OPA1, Fis1, Drp1).
- Evaluation of kidney regeneration markers (PCNA, GDF11) and autophagy/mitophagy markers (LC3 II/LC3 I, beclin-1, PINK-1, mitochondrial ubiquitination).
Main Results:
- Calorie restriction (CR) demonstrated significant nephroprotection in OXYS rats subjected to ischemic AKI.
- CR modulated the levels of anti- and proapoptotic proteins and affected protein acetylation and carbonylation.
- Evidence suggests CR enhances mitochondrial function, indicated by changes in mitochondrial dynamics and deacetylase activity.
Conclusions:
- Calorie restriction (CR) confers significant protection against ischemic acute kidney injury (AKI) in a model of accelerated aging.
- The beneficial effects of CR in AKI appear to involve the modulation of apoptotic pathways, protein modifications, and enhanced mitochondrial function.
- Improved mitochondrial functioning is proposed as a primary mechanism mediating the nephroprotective effects of CR in aging kidneys.
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