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

Abstract

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-X L 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.

Age-Related Changes in Bone-Marrow Mesenchymal Stem Cells

“…Thus, it is not easy to attribute the ultrastructure of mitochondria to their quality, but we can assume that the predominant condensed state of the mitochondrial matrix in cells taken from young animals may correspond to a more active turnover of ATP, which leads to a higher activity of ATP synthase associated with active proliferative capacity. Earlier, we underwent the analysis of mitochondrial ultrastructure in tubular renal cells, confirming the partial rejuvenating effect of diet restriction [ 38 ]. While the mitochondria in MSC taken from young animals had a condensed configuration, in cells from old rats, the configuration shifted to a more orthodox state, which we interpreted as a transition to a state of mitochondria with lower membrane potential.…”

“…Within these frames, reducing energy expenditure in its practical form, expressed as caloric restrictions, can potentially lead to a longer existence of the biological system, and at least slow down the aging process [ 54 ]. To some extent, the lower energy yield observed in this study in pMSC, due to the change in contribution of the glycolytic pathway to the total metabolism, is able to provide both adaptive healthy properties [ 38 ] and a longer life [ 55 ]. Ultimately, presumably acquired anti-senescence mechanisms in stem cells may provide the speed of aging at a rather low level, which requires further detailed investigation.…”

Dietary Restriction for Kidney Protection: Decline in Nephroprotective Mechanisms During Aging

“…However, we showed in the renal model of I/R, that in old rats DR for 1 or 2 months was not as effective as in young and did not reduce AKI measured by the level of serum creatinine and urea, as well as NGAL level in urine (Andrianova et al, 2018(Andrianova et al, , 2020. The loss of DR effectiveness during aging is more likely to have a gradual pattern since in 12-month-old rats DR still demonstrated some nephroprotective effect, but to a lesser extent than in young animals (Andrianova et al, 2020).…”

“…Most fruitful experimental studies of various DR protocols have been conducted in young animals (Singh and Krishan, 2019), while a few studies of DR protection in renal injury have shown a decline in beneficial effects with age (Andrianova et al, 2018(Andrianova et al, , 2020. This raises the question of implementation of DR in clinical practice since elderly people predominate among patients with AKI, so additional studies are needed to improve the effectiveness of DR for the aged kidney.…”

“…Subsequently, the protective effects of DR in ischemic AKI have been shown in a number of studies. We compared different DR protocols (25 and 35% DR for 4 weeks and 100% DR for 3 days) and found that 35% DR provided the maximum protective effect against I/R injury ( Andrianova et al, 2020 ). Later, it was shown that reduced food intake for 6 weeks regardless of time or fat affords protection of young mice against renal I/R ( Reynolds et al, 2019 ).…”