Research Paper Volume 12, Issue 18 pp 18693—18715

Resemblance and differences in dietary restriction nephroprotective mechanisms in young and old rats

Nadezda V. Andrianova1,2, , Ljubava D. Zorova1,3, , Irina B. Pevzner1,3, , Vasily A. Popkov1,3, , Valery P. Chernikov4, , Denis N. Silachev1,3, , Egor Y. Plotnikov1,3,5, , Dmitry B. Zorov1,3, ,

  • 1 A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119992, Russia
  • 2 Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow 119992, Russia
  • 3 V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow 117997, Russia
  • 4 Research Institute of Human Morphology, Moscow 117418, Russia
  • 5 Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Moscow 119991, Russia

Received: May 19, 2020       Accepted: July 21, 2020       Published: September 24, 2020
How to Cite

Copyright: © 2020 Andrianova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Dietary restriction (DR) is the strategy ameliorating the morbidity of various pathologies, including age-associated diseases. Acute kidney injury (AKI) remains a problem for the elderly with DR being a promising approach for diminishing its consequences. We evaluated the possible nephroprotective potential of short-term DR in young and old rats. DR in young rats resulted in pronounced beneficial effects normalizing lipid metabolism (triglycerides concentration, adiponectin level) activating autophagic-lysosomal system evaluated by LC3II/LC3I ratio, LAMP1, p62/SQSTM1 levels, and LysoTracker Green staining. DR had a remarkable recovering effect on mitochondrial structure and functions including regaining of mitochondrial membrane potential, the elevation of SIRT-3, PGC-1α, Bcl-XL levels and partial restoration of ultrastructure. The beneficial effects of DR resulted in the mitigation of oxidative stress including a decrease in levels of protein carbonylation and lipid peroxidation. Aging led to decreased activity of autophagy, elevated oxidative stress and impaired kidney regenerative capacity. Eventually, in old rats, even 8-week DR was not able to ameliorate AKI, but it caused some rejuvenating effects including elevation of mitochondrial membrane potential and Bcl-XL levels, as well as lowered severity of the oxidative stress. Thus, the age-associated decline of protective signaling demands extended DR to achieve nephroprotective potential in old animals.


AKI: acute kidney injury; AL: ad libitum; Bcl-XL: B-cell lymphoma-extra large; Bcl-XS: B-cell lymphoma-extra short; BUN: blood urea nitrogen; CKD: chronic kidney disease; DCF: 2’:7’-dichlorodihydrofluorescein diacetate; DR: dietary restriction; I/R: ischemia/reperfusion; LAMP1: lysosomal-associated membrane protein 1; LC3: light chain 3; NGAL: neutrophil gelatinase-associated lipocalin; PCNA: proliferating cell nuclear antigen; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; ROS: reactive oxygen species; SCr: serum creatinine; SIRT-3: sirtuin 3; TMRE: tetramethylrhodamine ethyl ester.