Caloric restriction and aging: an update

Masoro, Edward J.

doi:10.1016/s0531-5565(00)00084-x

Cited by 559 publications

(332 citation statements)

References 27 publications

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“…The nature of the mechanisms by which CR affects life span of rodents, or why different strains of laboratory mice and rats respond differently to CR, is presently unknown. It has been variously speculated that attenuation of oxidative stress, modulation of glucose and insulin levels, modulation of energy metabolism responses, effects on body composition, or hormesis is responsible for the anti-aging action of CR (e.g., 14,15). The variation among genotypes in their sensitivity to CR reported herein may serve as an important tool in establishing the specificity of the relationship between these CR effects and the prolongation of life span.…”

Section: Discussionmentioning

confidence: 77%

Genotype and age influence the effect of caloric intake on mortality in mice

Forster

Morris

Sohal³

2003

FASEB j.

210

160

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Long-term caloric restriction (CR) has been repeatedly shown to increase life span and delay the onset of age-associated pathologies in laboratory mice and rats. The purpose of the current study was to determine whether the CR-associated increase in life span occurs in all strains of mice or only in some genotypes and whether the effects of CR and ad libitum (AL) feeding on mortality accrue gradually or are rapidly inducible and reversible. In one experiment, groups of male C57BL/6, DBA/ 2, and B6D2F 1 mice were fed AL or CR (60% of AL) diets beginning at 4 months of age until death. In the companion study, separate groups of mice were maintained chronically on AL or CR regimens until 7, 17, or 22-24 months of age, after which, half of each AL and CR group was switched to the opposite regimen for 11 wk. This procedure yielded four experimental groups for each genotype, namely AL→AL, AL→CR, CR→CR, and CR→AL, designated according to long-term and shortterm caloric regimen, respectively. Long-term CR resulted in increased median and maximum life span in C57BL/6 and B6D2F 1 mice but failed to affect either parameter in the DBA/2 mice. The shift from AL→CR increased mortality in 17-and 24-month-old mice, whereas the shift from CR→AL did not significantly affect mortality of any age group. Such increased risk of mortality following implementation of CR at older ages was evident in all three strains but was most dramatic in DBA/ 2 mice. Results of this study indicate that CR does not have beneficial effects in all strains of mice, and it increases rather than decreases mortality if initiated in advanced age.Keywords caloric restriction; aging; C57BL/6; DBA/2; B6D2F 1 Caloric restriction (CR), compared with ad libitum (AL) feeding, has been shown to increase the life span of laboratory mice and rats (e.g., 1,2-4). For instance, a 40% decrease in total caloric intake, implemented after 3 months of age, has been found to increase the life span of C57BL/6 mice by more than 35% (5), and comparable findings have been made in Fischer 344 rats (4). Because CR produces such robust extensions in both the average and maximum life span, this regimen is widely assumed to provide a model for understanding the fundamental causes of the aging process. Notwithstanding, understanding of the mechanism by which CR retards the progression of age-related alterations has remained elusive even though several hypotheses have been proffered. A fundamental, but as yet, unresolved issue pertaining to the elucidation of the putative mechanism is whether the effects of CR accrue gradually or are they rapidly inducible and reversible upon shifting from AL feeding to the CR regimen and vice versa.Another issue critical to understanding the mechanistic basis of CR effects on aging is whether CR causes life span extension in virtually all animal species or only in some genotypes. The majority of previous studies on the effects of CR have been conducted on relatively few strains of rats and mice in which CR has been well established to result in...

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Section: Discussionmentioning

confidence: 77%

Genotype and age influence the effect of caloric intake on mortality in mice

Forster

Morris

Sohal³

2003

FASEB j.

210

160

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“…Lifelong moderate caloric restriction, ranging from 30%-40% less than ad libitum feeding without malnutrition, attenuates age-associated muscular atrophy (McKiernan et al, 2004) and enhances the life span of rodents and primates (Holloszy, 1997;Masoro, 1995Masoro, , 2000McCarter et al, 1997;Merry, 2002). McKiernan et al (2004) found that lifelong 40% caloric restriction results in a significant decrease in the rate of muscle mass loss, and attenuates age-induced fiber loss.…”

Section: Introductionmentioning

confidence: 99%

Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat

Kim

Kwak

Leeuwenburgh

et al. 2008

Experimental Gerontology

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Muscle atrophy is a highly prevalent condition among older adults, and results from reduced muscle mass and fiber cross-sectional area. Resistive exercise training and moderate (30-40%) caloric restriction may reduce the rate of sarcopenia in animal models. We tested the hypothesis that lifelong, voluntary exercise combined with mild (8%) caloric restriction would attenuate the reduction of muscle fiber cross-sectional area in the rat plantaris. Fischer-344 rats were divided into: young adults (6 mo.) fed ad libitum (YAL); 24 mo. old fed ad libitum (OAL); 24 mo. old on 8% caloric restriction (OCR); lifelong wheel running with 8% CR (OExCR). Plantaris fiber cross-sectional area was significantly lower in OAL than YAL (−27%), but protected in OCR and OExCR, while mass/body mass ratio was preserved in OExCR only. Furthermore, 8% CR and lifelong wheel running attenuated the age-induced increases in extramyocyte space and connective tissue. Citrate synthase activity decreased with age, but was not significantly protected in OCR and OExCR. Total hydroperoxides were higher in OAL than YAL, but were not elevated in OExCR, with no change in MnSOD. IGF-1 levels were lower in OAL (−57%) than YAL, but partially protected in the OExCR group (+51%).

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“…Genome-wide analysis of mouse brain indicates an up-regulation of inflammatory response and oxidative stress genes (Lee et al ., 2000). Caloric restriction, an environmental manipulation that slows the rate of aging (Sohal & Weindruch, 1996;Masoro, 2000) prevents some of the age-related changes in gene expression (Dhahbi et al ., 1999;Lee et al ., 1999Lee et al ., , 2000Kayo et al ., 2001;Pletcher et al ., 2002).…”

Section: Introductionmentioning

confidence: 99%

Spatio‐temporal analysis of gene expression during aging in Drosophila melanogaster

et al. 2002

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SummaryThe relationship between gene expression and the regulation of longevity is poorly understood. Previous studies focusing on microarray or tissue-specific changes in gene expression as a function of age have provided evidence that gene expression is a dynamic process which is regulated, even late in an organism's lifespan. Using the enhancer-trap technique, a systematic analysis of the spatio-temporal regulation of gene expression in tissues of adult Drosophila is presented. As many as 80% of enhancer traps analysed displayed (some form of) transcriptional change with age. In some cases the rate of change in expression was found to correlate with changes in longevity under various conditions, suggesting that they may be indicators of 'physiological age' and therefore valuable markers for dissecting the aging process. Molecular analysis of enhancer traps that showed increased activity with age was performed to identify candidate genes that may be important in the regulation of longevity; we identified changes in reporters associated with immunity, microtubule organization and muscle function.

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Caloric restriction and aging: an update

Cited by 559 publications

References 27 publications

Genotype and age influence the effect of caloric intake on mortality in mice

Genotype and age influence the effect of caloric intake on mortality in mice

Lifelong exercise and mild (8%) caloric restriction attenuate age-induced alterations in plantaris muscle morphology, oxidative stress and IGF-1 in the Fischer-344 rat

Spatio‐temporal analysis of gene expression during aging in Drosophila melanogaster

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