Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury

Andrianova, Nadezda V.; Jankauskas, Stanislovas S.; Zorova, Ljubava D.; Pevzner, Irina B.; Popkov, Vasily A.; Silachev, D. N.; Plotnikov, Egor Y.; Zorov, Dmitry B.

doi:10.3390/cells7100178

Cited by 19 publications

(13 citation statements)

References 76 publications

(95 reference statements)

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“…Caloric restriction in AKI with rats of different ages suggests that the caloric restriction can significantly increase autophagy activation by increasing LC3-I/LC3-II ratio and improving renal function. The nephroprotection effects gradually decline with the age due to deteriorations of the autophagic system [103]. The mTOR pathway acts as a two-way regulator during starvation and caloric restriction in rat.…”

Section: Autophagy In Chronic Kidney Diseasementioning

confidence: 99%

Autophagy in Chronic Kidney Diseases

Lin

Wang

2019

Cells

122

101

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Autophagy is a cellular recycling process involving self-degradation and reconstruction of damaged organelles and proteins. Current evidence suggests that autophagy is critical in kidney physiology and homeostasis. In clinical studies, autophagy activations and inhibitions are linked to acute kidney injuries, chronic kidney diseases, diabetic nephropathies, and polycystic kidney diseases. Oxidative stress, inflammation, and mitochondrial dysfunction, which are implicated as important mechanisms underlying many kidney diseases, modulate the autophagy activation and inhibition and lead to cellular recycling dysfunction. Abnormal autophagy function can induce loss of podocytes, damage proximal tubular cells, and glomerulosclerosis. After acute kidney injuries, activated autophagy protects tubular cells from apoptosis and enhances cellular regeneration. Patients with chronic kidney diseases have impaired autophagy that cannot be reversed by hemodialysis. Multiple nephrotoxic medications also alter the autophagy signaling, by which the mechanistic insights of the drugs are revealed, thus providing the unique opportunity to manage the nephrotoxicity of these drugs. In this review, we summarize the current concepts of autophagy and its molecular aspects in different kidney cells pathophysiology. We also discuss the current evidence of autophagy in acute kidney injury, chronic kidney disease, toxic effects of drugs, and aging kidneys. In addition, we examine therapeutic possibilities targeting the autophagy system in kidney diseases.

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Section: Autophagy In Chronic Kidney Diseasementioning

confidence: 99%

Autophagy in Chronic Kidney Diseases

Lin

Wang

2019

Cells

122

101

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“…Thus, old rats that received 60% of normal food intake for 2 months showed decreased blood urea nitrogen and serum creatinine levels, reduced renal tubular necrosis, and lower incidence of activated caspase-3 and TUNEL-positive cells in kidneys after cisplatin-induced nephrotoxicity ( Ning et al, 2013a ). 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 , 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 ).…”

Section: Dietary Restriction In Old Animalsmentioning

confidence: 70%

“…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.…”

Section: Possible Mechanisms Of Dietary Restriction Impairment During Agingmentioning

confidence: 99%

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

et al. 2021

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Dietary restriction (DR) is believed to be one of the most promising approaches to extend life span of different animal species and to delay deleterious age-related physiological alterations and diseases. Among others, DR was shown to ameliorate acute kidney injury (AKI) and chronic kidney disease (CKD). However, to date, a comprehensive analysis of the mechanisms of the protective effect of DR specifically in kidney pathologies has not been carried out. The protective properties of DR are mediated by a range of signaling pathways associated with adaptation to reduced nutrient intake. The adaptation is accompanied by a number of metabolic changes, such as autophagy activation, metabolic shifts toward lipid utilization and ketone bodies production, improvement of mitochondria functioning, and decreased oxidative stress. However, some studies indicated that with age, the gain of DR-mediated positive remodeling gradually decreases. This may be an obstacle if we seek to translate the DR approach into a clinic for the treatment of kidney diseases as most patients with AKI and CKD are elderly. It is well known that aging is accompanied by impairments in a huge variety of organs and systems, such as hormonal regulation, stress sensing, autophagy and proteasomal activity, gene expression, and epigenome profile, increased damage to macromolecules and organelles including mitochondria. All these age-associated changes might be the reasons for the reduced protective potential of the DR during aging. We summarized the available mechanisms of DR-mediated nephroprotection and described ways to improve the effectiveness of this approach for an aged kidney.

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“…An urgent problem in translation of IPC into clinical practice is a pronounced drop of IPC efficiency with age. Initially, this phenomenon was demonstrated for heart [3] and brain [8], but lately it was also observed in aging kidney [4,13]. At present, the reasons underlying declination of IPC effectiveness are yet unknown, but several hypothetical mechanisms are advanced.…”

Section: Age-relating Degradation Of Ischemic Tolerancementioning

confidence: 99%

Ischemic Preconditioning of the Kidney

Plotnikov

2021

Bull Exp Biol Med

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The phenomenon of ischemic preconditioning was discovered in 1986 in experiments with the heart, and then it was observed in almost all organs, the kidneys included. This phenomenon is underlain by conditioning of the tissues with short ischemia/reperfusion cycles intended for subsequent exposure to pathological ischemia. Despite the kidneys are not viewed as so vital organs as the brain or the heart, the acute ischemic injury to kidneys is a widespread pathology responsible for the yearly death of almost 2 million patients, while the number of patients with chronic kidney disease is estimated as hundreds of millions or nearly 10% adult population the world over. Currently, it is believed that adaptation of the kidneys to ischemia by preconditioning is the most effective way to prevent the development of acute kidney injury, so deep insight into its molecular mechanisms will be a launch pad for creating the nephroprotective therapy by elevating renal tolerance to oxygen deficiency. This review focuses on the key signaling pathways of kidney ischemic preconditioning, the potential pharmacological mimetics of its key elements, and the limitations of this therapeutic avenue associated with age-related decline of ischemic tolerance of the kidneys.

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Mechanisms of Age-Dependent Loss of Dietary Restriction Protective Effects in Acute Kidney Injury

Cited by 19 publications

References 76 publications

Autophagy in Chronic Kidney Diseases

Autophagy in Chronic Kidney Diseases

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

Ischemic Preconditioning of the Kidney

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