Mechanisms of the anti-aging and prolongevity effects of caloric restriction: evidence from studies of genetically modified animals

Hoshino, Shunsuke; Kobayashi, Masaki; Higami, Yoshikazu

doi:10.18632/aging.101557

Cited by 21 publications

(23 citation statements)

References 49 publications

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“…Previous research has reported a link between sirtuins and mitochondrial function and abnormal tau proteins and amyloid. It was confirmed that SIRT1, 3, and 6 are involved in age-related disease and regulation of life span, as well as AD progression ( Hoshino et al, 2018 ). In mice model of AD, accompanied by impaired DNA repair, the precursor of NAD + , nicotinamide riboside (NR), increases SIRT3 and SIRT6 ( Hou et al, 2018 ).…”

Section: Calorie Restriction and Cognitive And Social Determinants Ofmentioning

confidence: 90%

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

et al. 2021

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Over the past decades, the human life span has dramatically increased, and therefore, a steady increase in diseases associated with age (such as Alzheimer’s disease and Parkinson’s disease) is expected. In these neurodegenerative diseases, there is a cognitive decline and memory loss, which accompany increased systemic inflammation, the inflamm-aging, and the insulin resistance. Despite numerous studies of age-related pathologies, data on the contribution of brain insulin resistance and innate immunity components to aging are insufficient. Recently, much research has been focused on the consequences of nutrients and adiposity- and nutrient-related signals in brain aging and cognitive decline. Moreover, given the role of metainflammation in neurodegeneration, lifestyle interventions such as calorie restriction may be an effective way to break the vicious cycle of metainflammation and have a role in social behavior. The various effects of calorie restriction on metainflammation, insulin resistance, and neurodegeneration have been described. Less attention has been paid to the social determinants of aging and the possible mechanism by which calorie restriction might influence social behavior. The purpose of this review is to discuss current knowledge in the interdisciplinary field of geroscience—immunosenescence, inflamm-aging, and metainflammation—which makes a significant contribution to aging. A substantial part of the review is devoted to frontiers in the brain insulin resistance in relation to neuroinflammation. In addition, we summarize new data on potential mechanisms of calorie restriction that influence as a lifestyle intervention on the social brain. This knowledge can be used to initiate successful aging and slow the onset of neurodegenerative diseases.

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Section: Calorie Restriction and Cognitive And Social Determinants Ofmentioning

confidence: 90%

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

et al. 2021

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“…Although there is no system equivalent to GH in lower organisms such as yeast, worms, and flies [120], a number of observations reported for the last two decades strongly support the idea that downregulation of IIS and activation of FOXO transcription factors extend lifespan in these animal models (reviewed in [120,159,162,163]). In fact, of the > 40 genetic mutations that have been reported to extend lifespan in the mouse and the rat models, approximately one third of them are involved in GH and IIS [164]. Because CR reduces GH and IIS [164], it is generally accepted that CR extends lifespan by limiting GH/IIS signaling and subsequently expressing pro-longevity genes by activating FOXO transcription factors [165].…”

Section: Iis-foxo Signalingmentioning

confidence: 99%

“…In fact, of the > 40 genetic mutations that have been reported to extend lifespan in the mouse and the rat models, approximately one third of them are involved in GH and IIS [164]. Because CR reduces GH and IIS [164], it is generally accepted that CR extends lifespan by limiting GH/IIS signaling and subsequently expressing pro-longevity genes by activating FOXO transcription factors [165]. To date, there are mixed results reported for the question of whether the IIS-FOXO signaling cascade is responsible for CR-mediated lifespan extension.…”

Section: Iis-foxo Signalingmentioning

confidence: 99%

Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms

et al. 2020

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Genetic and pharmacological interventions have successfully extended healthspan and lifespan in animals, but their genetic interventions are not appropriate options for human applications and pharmacological intervention needs more solid clinical evidence. Consequently, dietary manipulations are the only practical and probable strategies to promote health and longevity in humans. Caloric restriction (CR), reduction of calorie intake to a level that does not compromise overall health, has been considered as being one of the most promising dietary interventions to extend lifespan in humans. Although it is straightforward, continuous reduction of calorie or food intake is not easy to practice in real lives of humans. Recently, fasting-related interventions such as intermittent fasting (IF) and time-restricted feeding (TRF) have emerged as alternatives of CR. Here, we review the history of CR and fasting-related strategies in animal models, discuss the molecular mechanisms underlying these interventions, and propose future directions that can fill the missing gaps in the current understanding of these dietary interventions. CR and fasting appear to extend lifespan by both partially overlapping common mechanisms such as the target of rapamycin (TOR) pathway and circadian clock, and distinct independent mechanisms that remain to be discovered. We propose that a systems approach combining global transcriptomic, metabolomic, and proteomic analyses followed by genetic perturbation studies targeting multiple candidate pathways will allow us to better understand how CR and fasting interact with each other to promote longevity.

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“…The animals that emerge from dauer undergo rapid catch-up development to achieve reproductive maturity in a few days and eventually die at the usual developmental age in 1-2 weeks. Caloric restriction in vertebrates produces a similar slowing of the biological clock associated with aging [27,86].…”

Section: Hyperpurinergic Hypometabolism and The Biological Clocks Of mentioning

confidence: 99%

Metabolic and Behavioral Features of Acute Hyperpurinergia and the Connection to Autism Spectrum Disorder

Zolkipli‐Cunningham

Naviaux

Nakayama

et al. 2020

Preprint

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Background. Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Methods. Responses were studied in C57BL/6J mice with ASD-like behaviors in the maternal immune activation (MIA) model and controls. Basal metabolic rates, respiratory exchange ratios (RER = VCO2/VO2), and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Results. A 0.5 µmol/g dose of ATP dropped whole body oxygen consumption by 74% ± 6% (mean ± SEM, 5,303 to 1,382 ml/kg/hr, p<0.0001) and rectal temperature by 6.2˚ ± 0.3˚C (p<0.0001) in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. MIA animals were hypersensitive to the metabolic and behavioral responses triggered by eATP and poly(IC). Breathomic and metabolomic analysis revealed changes in folate-methylation-1-carbon, purines, pyrimidines, acyl-carnitines, glycolysis, aromatic and branch-chain amino acids, Krebs cycle, glutathione, urea cycle, phospholipids, sphingolipids, eicosanoids, cholesterol, bile acids, vitamins, and microbiome metabolism similar to children with ASD. Limitations. The responses to ATP were studied in only a single genetic strain of mice (C57BL/6J). Although similar to metabolic results reported in FVB mice and a small clinical trial in children with ASD, the generalizability of these results to larger studies in humans is unknown. The chronic effects of repeated postnatal ATP exposures were not tested. Conclusions. Acute hyperpurinergia produced metabolic and behavioral changes in mice that were similar to those found in children with ASD. These behaviors and metabolic changes were associated with mitochondrial functional changes that were profound but reversible.

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Mechanisms of the anti-aging and prolongevity effects of caloric restriction: evidence from studies of genetically modified animals

Cited by 21 publications

References 49 publications

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

Inflamm-Aging and Brain Insulin Resistance: New Insights and Role of Life-style Strategies on Cognitive and Social Determinants in Aging and Neurodegeneration

Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms

Metabolic and Behavioral Features of Acute Hyperpurinergia and the Connection to Autism Spectrum Disorder

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