Molecular Mechanisms of Longevity Regulation and Calorie Restriction

2006 ◽  
pp. 207-218
Author(s):  
Su-Ju Lin
Keyword(s):  
Calorie Restriction ◽  
Molecular Mechanisms

Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention

2007 ◽  
Vol 32 (5) ◽  
pp. 954-966 ◽  
Author(s):  
Christy S. Carter ◽  
Tim Hofer ◽  
Arnold Y. Seo ◽  
Christian Leeuwenburgh
Keyword(s):  
Life Span ◽  
Calorie Restriction ◽  
Aging Process ◽  
Molecular Mechanisms ◽  
Geriatric Medicine ◽  
Functional Decline ◽  
Intervention Strategies ◽  
Health Span ◽  
Structural Deterioration ◽  
Age Related

The aging process results in a gradual and progressive structural deterioration of biomolecular and cellular compartments and is associated with many pathological conditions, including cardiovascular disease, stroke, Alzheimer’s disease, osteoporosis, sarcopenia, and liver dysfunction. Concomitantly, each of these conditions is associated with progressive functional decline, loss of independence, and ultimately disability. Because disabled individuals require care in outpatient or home care settings, and in light of the social, emotional, and fiscal burden associated with caring for an ever-increasing elderly population, research in geriatric medicine has recently focused on the biological mechanisms that are involved in the progression towards functional decline and disability to better design treatment and intervention strategies. Although not completely understood, the mechanisms underlying the aging process may partly involve inflammatory processes, oxidative damage, mitochondrial dysfunction, and apoptotic tissue degeneration. These hypotheses are based on epidemiological evidence and data from animal models of aging, as well as interventional studies. Findings from these studies have identified possible strategies to decrease the incidence of age-related diseases and delay the aging process. For example, lifelong exercise is known to extend mean life-span, whereas calorie restriction (CR) increases both mean and maximum life-span in a variety of species. Optimal application of these intervention strategies in the elderly may positively affect health-related outcomes and possibly longevity. Therefore, the scope of this article is to (i) provide an interpretation of various theories of aging from a “health-span” perspective; (ii) describe interventional testing in animals (CR and exercise); and (iii) provide a translational interpretation of these data.

scholarly journals Intrauterine calorie restriction affects placental DNA methylation and gene expression

2013 ◽  
Vol 45 (14) ◽  
pp. 565-576 ◽  
Author(s):  
Pao-Yang Chen ◽  
Amit Ganguly ◽  
Liudmilla Rubbi ◽  
Luz D. Orozco ◽  
Marco Morselli ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Chronic Diseases ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Specific Effects ◽  
Differentially Methylated Genes ◽  
Critical Organ ◽  
Successive Generations

Maternal nutrient restriction causes the development of adult onset chronic diseases in the intrauterine growth restricted (IUGR) fetus. Investigations in mice have shown that either protein or calorie restriction during pregnancy leads to glucose intolerance, increased fat mass, and hypercholesterolemia in adult male offspring. Some of these phenotypes are shown to persist in successive generations. The molecular mechanisms underlying IUGR remain unclear. The placenta is a critical organ for mediating changes in the environment and the development of embryos. To shed light on molecular mechanisms that might affect placental responses to differing environments we examined placentas from mice that had been exposed to different diets. We measured gene expression and whole genome DNA methylation in both male and female placentas of mice exposed to either caloric restriction or ad libitum diets. We observed several differentially expressed pathways associated with IUGR phenotypes and, most importantly, a significant decrease in the overall methylation between these groups as well as sex-specific effects that are more pronounced in males. In addition, a set of significantly differentially methylated genes that are enriched for known imprinted genes were identified, suggesting that imprinted loci may be particularly susceptible to diet effects. Lastly, we identified several differentially methylated microRNAs that target genes associated with immunological, metabolic, gastrointestinal, cardiovascular, and neurological chronic diseases, as well as genes responsible for transplacental nutrient transfer and fetal development.

scholarly journals Does Calorie Restriction Modulate Inflammaging via FoxO Transcription Factors?

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1959
Author(s):  
Sang-Eun Kim ◽  
Ryoichi Mori ◽  
Isao Shimokawa
Keyword(s):  
Transcription Factors ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Functional Decline ◽  
Cell Lineage ◽  
Myeloid Cell ◽  
The Body ◽  
Pyrin Domain ◽  
Foxo Transcription Factors

Calorie restriction (CR) has been shown to extend lifespan and retard aging-related functional decline in animals. Previously, we found that the anti-neoplastic and lifespan-extending effects of CR in mice are regulated by forkhead box O transcription factors (FoxO1 and FoxO3), located downstream of growth hormone (GH)–insulin-like growth factor (IGF)-1 signaling, in an isoform-specific manner. Inflammaging is a term coined to represent that persistent low-level of inflammation underlies the progression of aging and related diseases. Attenuation of inflammaging in the body may underlie the effects of CR. Recent studies have also identified cellular senescence and activation of the nucleotide-binding domain, leucine-rich-containing family, pyrin-domain-containing-3 (NLRP3) inflammasome as causative factors of inflammaging. In this paper, we reviewed the current knowledge of the molecular mechanisms linking the effects of CR with the formation of inflammasomes, particularly focusing on possible relations with FoxO3. Inflammation in the brain that affects adult neurogenesis and lifespan was also reviewed as evidence of inflammaging. A recent progress of microRNA research was described as regulatory circuits of initiation and propagation of inflammaging. Finally, we briefly introduced our preliminary results obtained from the mouse models, in which Foxo1 and Foxo3 genes were conditionally knocked out in the myeloid cell lineage.

scholarly journals Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels

2011 ◽  
Vol 2011 ◽  
pp. 1-16 ◽  
Author(s):  
Bin Li ◽  
Craig Skinner ◽  
Pablo R. Castello ◽  
Michiko Kato ◽  
Erin Easlon ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Calorie Restriction ◽  
Mitochondrial Respiration ◽  
Molecular Mechanisms ◽  
Mitochondrial Respiratory Chain ◽  
Yeast Cells ◽  
Mitochondrial Activity ◽  
No Production ◽  
Hypoxic Conditions ◽  
Yeast Mutants

Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and studySaccharomyces cerevisiaemutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. CR-increased NO is largely dependent on mitochondrial electron transport and cytochrome c oxidase (COX). Although COX normally produces NO under hypoxic conditions, CR-treated yeast cells are able to produce NO under normoxic conditions. Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan.

scholarly journals Intragenic repeat expansions control yeast chronological aging

2019 ◽  
Author(s):  
Benjamin P Barré ◽  
Johan Hallin ◽  
Jia-Xing Yue ◽  
Karl Persson ◽  
Ekaterina Mikhalev ◽  
...  
Keyword(s):  
Life Span ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Tandem Repeats ◽  
Repeat Expansion ◽  
Yeast Cells ◽  
Chronological Aging ◽  
Cellular Life ◽  
Chronological Life Span ◽  
Repeat Expansions

ABSTRACTAging varies among individuals due to both genetics and environment but the underlying molecular mechanisms remain largely unknown. Using a highly recombinedSaccharomyces cerevisiaepopulation, we found 30 distinct Quantitative Trait Loci (QTLs) that control chronological life span (CLS) in calorie rich and calorie restricted environments, and under rapamycin exposure. Calorie restriction and rapamycin extended life span in virtually all genotypes, but through different genetic variants. We tracked the two major QTLs to massive expansions of intragenic tandem repeats in the cell wall glycoproteinsFLO11andHPF1, which caused a dramatic life span shortening. Life span impairment by N-terminalHPF1repeat expansion was partially buffered by rapamycin but not by calorie restriction. TheHPF1repeat expansion shifted yeast cells from a sedentary to a buoyant state, thereby increasing their exposure to surrounding oxygen. The higher oxygenation perturbed methionine, lipid, and purine metabolism, which likely explains the life span shortening. We conclude that fast evolving intragenic repeat expansions can fundamentally change the relationship between cells and their environment with profound effects on cellular life style and longevity.

scholarly journals Improved insulin sensitivity by calorie restriction is associated with reduction of ERK and p70S6K activities in the liver of obese Zucker rats

2009 ◽  
Vol 203 (3) ◽  
pp. 337-347 ◽  
Author(s):  
Yanbin Zheng ◽  
Wenshuo Zhang ◽  
Elisha Pendleton ◽  
Sanhua Leng ◽  
Jiong Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Kinase Assay ◽  
Zucker Rats ◽  
Obese Rats ◽  
Irs Proteins ◽  
Threonine Kinases

Calorie restriction (CR) improves obesity-related insulin resistance through undefined molecular mechanisms. Insulin receptor substrate (IRS)-1 serine/threonine kinases have been proposed to modulate insulin sensitivity through phosphorylation of IRS proteins. The aim of this study is to test the hypothesis that changes in the activity of IRS1 serine/threonine kinases may underlie the molecular mechanism of CR in improving insulin sensitivity. Obese and lean Zucker rats were subjected to 40% CR or allowed to feed ad libitum (AL) for 20 weeks; body weight and insulin sensitivity were monitored throughout this period. The activity of IRS1 serine/threonine kinases – including JNK, ERK, MTOR/p70S6K (RPS6KB1 as listed in the MGI Database), glycogen synthase kinase 3β (GSK3B), AMPK (PRKAA1 as listed in the MGI Database), and protein kinase Cθ (PRKCQ) in liver tissue extracts was measured by an in vitro kinase assay using various glutathione-S-transferase (GST)–IRS1 fragments as substrates, while phosphorylation of IRS1 and serine kinases was determined by western blotting using phosphospecific antibodies. CR in obese rats significantly reduced body weight and increased insulin sensitivity compared to AL controls. Serine kinase activity toward IRS1S612 (corresponding to S616 in human IRS1) and IRS1S632/635 (corresponding to S636/639 in human IRS1) was increased in obese rats compared to lean littermates, and was markedly decreased following CR. Concomitantly, obesity increased and CR decreased the activity of hepatic ERK and p70S6K against IRS1. The close association between the activity of hepatic ERK and p70S6K with insulin resistance suggests an important role for ERK and p70S6K in the development of insulin resistance, presumably via phosphorylation of IRS proteins.

Identification of immune-related genes in thymus of breast cancer mouse model exposed to different calorie restriction

2019 ◽  
Vol 44 (5) ◽  
pp. 635-645
Author(s):  
Zehra Omeroglu Ulu ◽  
Salih Ulu ◽  
Soner Dogan ◽  
Bilge Guvenc Tuna ◽  
Nehir Ozdemir Ozgenturk
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Calorie Restriction ◽  
Molecular Mechanisms ◽  
Transcriptional Profiling ◽  
Rna Seq ◽  
Expression Levels ◽  
Thymus Tissue ◽  
Different Types ◽  
Immune Related Genes

Abstract Introduction In the present study, RNA sequencing-mediated transcriptome analysis was performed in order to elucidate the molecular mechanisms of the immune response for different types of calorie restriction (CR) application using MMTV-TGF-α breast cancer mouse model. Methods Animals were applied to three different dietary regiments; ad libitum (AL), chronic calorie restriction (CCR) and intermittent calorie restriction (ICR). Using thymus tissues, 6091 differentially expressed genes (DEGs) were identified in three dietary groups. After clustering of total of 6091 DEGs using Gene Ontology (GO) categories, a total of 400 genes were identified to be involved in immune system process (GO:0002376) GO categories. KEGG pathway and gene co-expression network analysis of these immune-related DEGs were done using String database. The results were confirmed with measuring mRNA expression levels of four selected immune-related DEGs genes (Casp3, Thy1, IL-16 and CD4) using quantitative real-time PCR (qPCR). Results The expression levels of immune-related genes were different in three RNA-seq data. Conclusion The results provide useful information to investigate the immune-related transcriptional profiling in thymus tissue of breast cancer mouse model applied to two different types of CR and to identify the specific functional immune related genes in response to CR during cancer development.

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