Suppression of apoptosis by calorie restriction in aged kidney

Lee, Ji Hyeon; Jung, Kyung Jin; Kim, Jung Won; Kim, Hyon Jeen; Yu, Byung Pal; Chung, Hae Young

doi:10.1016/j.exger.2004.06.015

Cited by 63 publications

(49 citation statements)

References 51 publications

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“…Although our study lasted only 3 months, we observed trends in the glomeruli and renal tubules ofM-aged rats fed EAA similar to those obtained with CR (24). In particular, we detected reduced glomerular tufts in the M-aged group that were restored after EAA supplementation to the form in younger rats.…”

Section: Discussionsupporting

confidence: 52%

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Supplementation with Essential Amino Acids in Middle Age Maintains the Health of Rat Kidney

Corsetti

Stacchiotti

D’Antona

et al. 2010

Int J Immunopathol Pharmacol

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Chronic kidney diseases are a social and economic problem, and diet has long been recognized as a fundamental modulator of kidney health in human and experimental models. Age-dependent alterations in mitochondrial function playa crucial role in the development of diseases of aging, and mitochondrial disorders have been observed in experimental models of kidney failure. Recently, the beneficial dietary effect of a specific mixture of essential amino acids (EAA) has been studied in elderly subjects, but no data were collected from the kidney. The aim of this study was to assess whether daily supplementation of the diet with EAA at the beginning of senescence could preserve renal health. We used middle-aged (I8-month-old) male Wistar rats fed a standard diet and water ad libitum (M-aged group) or a diet with added EAA (1.5 g/kg per day) dissolved in drinking water for 3 months (M-aged+EAA group). Young (2-month-old) rats fed a standard diet for 3 months were used as controls. Mitochondrial morphology and markers for collagen, cyt-c-oxidase, HSP60, GRP75, eNOS, iNOS, Bax, Bel2 and VEGF were analyzed in glomeruli and tubules. EAA supplementation limited fibrosis and increased the capillary tuft area in the glomeruli of M-aged rats. VEGF and eNOS were enhanced in glomeruli and the peritubular space with the EAA-supplemented diet. Mitochondrial cyt-c oxidase, Bel2, and chaperones increased in the distal tubules of the EAA group to levels similar to those observed in the young group. Mitochondrial area and density after EAA intake did not differ from young groups. The results suggest that prolonged EAA intake could represent a strategy for maintaining the healthy status of the kidney in M-aged animals.Chronic kidney diseases (CKD) and their progression to end-stage renal disease (ESRD) are considerable social and economic problems in all industrialized countries. Each year in Italy, more than 18,000 patients are diagnosed as having CKD (1). The incidence of CKD is strictly linked to age: in patients over 75 years it was almost 7 times that in patients aged 20-39 years and more the twice that in patients aged 40-59 years (2). Therefore, interventions that may prevent the development of CKD in middle age are very important for public health.Reactive oxygen species (ROS) and nitrogen species are responsible for human aging

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Section: Discussionsupporting

confidence: 52%

“…The expression of the antiapoptotic Bel2 family members Bel-2, and proapoptotic molecule Bax in M-aged rats fed EAA are in agreement with those reported by Lee et at. (24) after CR. It has been suggested that the benefit of CR may partly derive from decreased mitochondrial ROS production and oxidative damage (33).…”

Section: Discussionmentioning

confidence: 99%

Supplementation with Essential Amino Acids in Middle Age Maintains the Health of Rat Kidney

Corsetti

Stacchiotti

D’Antona

et al. 2010

Int J Immunopathol Pharmacol

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“…Importantly, CR attenuated the increased susceptibility of aged rats to renal injury in vitro, suggesting that the increased susceptibility is preventable. The effect of CR on aging nephropathy may be related to decreased protein intake, anti-oxidative action (48), suppression of renal tubular apoptosis (18), and decreased inflammatory infiltration (38) in aged animals. However, other data suggest that the development of glomerulosclerosis, which is attenuated by CR, does not influence the increased susceptibility to ischemia in the rat kidney (33).…”

Section: Discussionmentioning

confidence: 99%

Increased susceptibility of aging kidney to ischemic injury: identification of candidate genes changed during aging, but corrected by caloric restriction

Chen¹,

Bridenbaugh²,

Akintola³

et al. 2007

American Journal of Physiology-Renal Physiology

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Aging is associated with an increased incidence and severity of acute renal failure. However, the molecular mechanism underlying the increased susceptibility to injury remains undefined. These experiments were designed to investigate the influence of age on the response of the kidney to ischemic injury and to identify candidate genes that may mediate this response. Renal slices prepared from young (5 mo), aged ad libitum (aged-AL; 24 mo), and aged caloric-restricted (aged-CR; 24 mo) male Fischer 344 rats were subjected to ischemic stress (100% N2) for 0 -60 min. As assessed by biochemical and histological evaluation, slices from aged-AL rats were more susceptible to injury than young counterparts. Importantly, caloric restriction attenuated the increased susceptibility to injury. In an attempt to identify the molecular pathway(s) underlying this response, microarray analysis was performed on tissue harvested from the same animals used for the viability experiments. RNA was isolated and the corresponding cDNA was hybridized to CodeLink Rat Whole Genome Bioarray slides. Subsequent gene expression analysis was performed using GeneSpring software. Using two-sample t-tests and a twofold cut-off, the expression of 92 genes was changed during aging and attenuated by caloric restriction, including claudin-7, kidney injury molecule-1 (Kim-1), and matrix metalloproteinase-7 (MMP-7). Claudin-7 gene expression peaked at 18 mo; however, increased protein expression in certain tubular epithelial cells was seen at 24 mo. Kim-1 gene expression was not elevated at 8 or 12 mo but was at 18 and 24 mo. However, changes in Kim-1 protein expression were only seen at 24 mo and corresponded to increased urinary levels. Importantly, these changes were attenuated by caloric restriction. MMP-7 gene expression was decreased at 8 mo, but an age-dependent increase was seen at 24 mo. Increased MMP-7 protein expression in tubular epithelial cells at 24 mo was correlated with the gene expression pattern. In summary, we identified genes changed by aging and changes attenuated by caloric restriction. This will facilitate investigation into the molecular mechanism mediating the age-related increase in susceptibility to injury. ischemia; microarray analysis ISCHEMIA IS A LEADING cause of acute renal failure (ARF), which develops in ϳ4 -7% of hospitalized patients each year (20).Common conditions leading to ischemia include cardiovascular disease, stroke, dehydration, and surgery, all of which place the elderly population at risk for ischemic ARF. Although the mortality rates for ARF are decreasing, the rates still range from 20 to 35% (45, 47). Importantly, Xue et al. (47) established age as a risk factor for ARF. This is in agreement with previous studies that have associated age with a higher risk for ARF (25,29,30). Pascual et al. (26) suggested that the incidence of ARF is 3.5 times higher in patients over 70 and the aged patients had a higher mortality rate. However, little is known about the molecular mechanism(s) that underlie the age-depen...

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“…4 The impact of chronically reduced food intake has been shown to depend solely on the reduction of caloric intake, rather than intake of specific dietary nutrients. 5-7, but see 8 Several studies have indicated that the impact on lifespan occurs because CR attenuates the onset of many age-related diseases, particularly cancer, [9][10][11][12][13][14][15][16] but see 17 and generally reduces the expression of markers of agerelated decline in function. Hence, the effect on lifespan is a consequence of a true reduction in the rate of aging.…”

Section: Introductionmentioning

confidence: 99%

Hunger Does Not Diminish Over Time in Mice Under Protracted Caloric Restriction

Hambly¹,

Mercer²,

Speakman

2007

Rejuvenation Research

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Caloric restriction (CR) is the only nongenetic manipulation known to reliably prolong life-span. Modeling suggests that humans would need to restrict their intake for many years to reap any lifespan benefits. The feasibility of such prolonged restriction may hinge on whether hunger diminishes with the time period spent restricted. We used the magnitude of hyperphagia on release from restriction as a bioassay of hunger in restricted mice. During restriction, mice develop a characteristic pattern of neuropeptide signals in the arcuate nucleus that reflect their hunger. This pattern is normalized after the postrestriction hyperphagia, validating hyperphagia as an indicator of the hunger during restriction. Mice were food restricted (80% of ad lib.) for 50 days. They initially lost weight, but then became weight stable and were maintained in CR at this lower level of energy balance for between 0 and 50 days and were then fed ad lib. for 50 days. When released onto ad lib. food, the magnitude of the hyperphagic response was independent of the prior length of CR. Hyperphagia ended when body mass was normalized. Hunger therefore did not diminish even when they were restricted for 100 days, equivalent to about 11 years in humans. The pattern of hyperphagic response suggested that signals coding body mass drive hunger during restriction, and because body mass under restriction remains depressed, this suggests that hunger would never disappear, making restriction to prolong lifespan in humans difficult to accomplish.

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Suppression of apoptosis by calorie restriction in aged kidney

Cited by 63 publications

References 51 publications

Supplementation with Essential Amino Acids in Middle Age Maintains the Health of Rat Kidney

Supplementation with Essential Amino Acids in Middle Age Maintains the Health of Rat Kidney

Increased susceptibility of aging kidney to ischemic injury: identification of candidate genes changed during aging, but corrected by caloric restriction

Hunger Does Not Diminish Over Time in Mice Under Protracted Caloric Restriction

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