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.

Calorie Restriction and Aging

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-2-SCI-2
Author(s):  
Rafael de Cabo
Keyword(s):  
Oxidative Stress ◽  
Life Span ◽  
Calorie Restriction ◽  
Stress Proteins ◽  
Conflicts Of Interest ◽  
Caloric Intake ◽  
Tissue Growth ◽  
Age Related ◽  
Underlying Mechanisms ◽  
And Oxidative Stress

Abstract Abstract SCI-2 A prominent manifestation of aging is a reduced ability to respond to environmental stressors, including heat and oxidative stress. Reduced stress tolerance and decreased ability to maintain homeostasis are at least partially responsible for the increased morbidity and mortality that occurs with advancing age. The age-related attenuation of stress pathways and increased expression of stress-response genes with aging are examples of the growing body of evidence linking reduced stress responsiveness to aging. In 1935, McCay and colleagues first reported that reducing the caloric intake of rodents could significantly lengthen their mean and maximal life span, slowing down basic aging processes. The effect of calorie restriction (CR) on delaying aging has been replicated in many animal species including nonhuman primates, although in these, potential life span alterations cannot be ascertained for several more years due to their longevity CR causes a reduction in body weight, tissue growth, blood glucose, insulin levels and body temperature. In addition, CR prevents the age-related decline in tolerance to different stressors such as oxidative and heat, and the age-related reduction in expression of protective heat shock and oxidative stress proteins. While CR is the only intervention that has consistently been shown to increase maximum life span and prevent or delay the onset of age-associated pathophysiological changes in laboratory rodents, the underlying mechanisms remain elusive. Using calorie restriction (CR) as their benchmark research tool, gerontologists are making progress in identifying dietary and pharmacologic interventions that may be applicable to retarding aging processes in humans. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Linking Peroxiredoxin and Vacuolar-ATPase Functions in Calorie Restriction-Mediated Life Span Extension

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Mikael Molin ◽  
Ayse Banu Demir
Keyword(s):  
Life Span ◽  
Signaling Pathways ◽  
Calorie Restriction ◽  
Iron Homeostasis ◽  
Vacuolar Atpase ◽  
Beneficial Effects ◽  
Age Related ◽  
Nutrient Signaling ◽  
Physiological Benefits ◽  
Vacuolar Atpases

Calorie restriction (CR) is an intervention extending the life spans of many organisms. The mechanisms underlying CR-dependent retardation of aging are still poorly understood. Despite mechanisms involving conserved nutrient signaling pathways proposed, few target processes that can account for CR-mediated longevity have so far been identified. Recently, both peroxiredoxins and vacuolar-ATPases were reported to control CR-mediated retardation of aging downstream of conserved nutrient signaling pathways. In this review, we focus on peroxiredoxin-mediated stress-defence and vacuolar-ATPase regulated acidification and pinpoint common denominators between the two mechanisms proposed for how CR extends life span. Both the activities of peroxiredoxins and vacuolar-ATPases are stimulated upon CR through reduced activities in conserved nutrient signaling pathways and both seem to stimulate cellular resistance to peroxide-stress. However, whereas vacuolar-ATPases have recently been suggested to control both Ras-cAMP-PKA- and TORC1-mediated nutrient signaling, neither the physiological benefits of a proposed role for peroxiredoxins in H2O2-signaling nor downstream targets regulated are known. Both peroxiredoxins and vacuolar-ATPases do, however, impinge on mitochondrial iron-metabolism and further characterization of their impact on iron homeostasis and peroxide-resistance might therefore increase our understanding of the beneficial effects of CR on aging and age-related diseases.

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 Dietary Interventions to Extend Life Span and Health Span Based on Calorie Restriction

2010 ◽  
Vol 65A (7) ◽  
pp. 695-703 ◽  
Author(s):  
R. K. Minor ◽  
J. S. Allard ◽  
C. M. Younts ◽  
T. M. Ward ◽  
R. de Cabo
Keyword(s):  
Life Span ◽  
Calorie Restriction ◽  
Dietary Interventions ◽  
Health Span ◽  
Extend Life Span

scholarly journals Chondrocyte Aging: The Molecular Determinants and Therapeutic Opportunities

2021 ◽  
Vol 9 ◽  
Author(s):  
Thamil Selvee Ramasamy ◽  
Yong Mei Yee ◽  
Ilyas M. Khan
Keyword(s):  
Molecular Mechanisms ◽  
Articular Chondrocytes ◽  
Functional Decline ◽  
Cellular Aging ◽  
Joint Degeneration ◽  
Complex Interplay ◽  
Regenerative Capacity ◽  
Progressive Decline ◽  
Age Related ◽  
Molecular Determinants

Osteoarthritis (OA) is a joint degenerative disease that is an exceedingly common problem associated with aging. Aging is the principal risk factor for OA, but damage-related physiopathology of articular chondrocytes probably drives the mechanisms of joint degeneration by a progressive decline in the homeostatic and regenerative capacity of cells. Cellular aging is the manifestation of a complex interplay of cellular and molecular pathways underpinned by transcriptional, translational, and epigenetic mechanisms and niche factors, and unraveling this complexity will improve our understanding of underlying molecular changes that affect the ability of the articular cartilage to maintain or regenerate itself. This insight is imperative for developing new cell and drug therapies for OA disease that will target the specific causes of age-related functional decline. This review explores the key age-related changes within articular chondrocytes and discusses the molecular mechanisms that are commonly perturbed as cartilage ages and degenerates. Current efforts and emerging potential therapies in treating OA that are being employed to halt or decelerate the aging processes are also discussed.

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.

Potential Possibilities of Nuclear Medicine Methods in Diagnostics Age Changes of the Cardiovascular System.

2021 ◽  
Vol 66 (5) ◽  
pp. 59-65
Author(s):  
M. Vorontsova ◽  
A. Obrezan ◽  
A. Obrezan
Keyword(s):  
Aging Process ◽  
Molecular Mechanisms ◽  
The Body ◽  
Premature Aging ◽  
Diagnostic Methods ◽  
Age Changes ◽  
Medical Interventions ◽  
Defense Systems ◽  
Age Related ◽  
Daunting Task

In connection with the increase in the average age of the world's population, the problem of preventing premature aging and the treatment of age-related diseases is coming to the fore. The main direction in the implementation of this goal is to influence the key molecular mechanisms of aging in order to suppress pathological processes and activate the defense systems of the cell and the body as a whole. In order to solve this daunting task, it is necessary to have in the arsenal not only various means of intervention in the aging process, but also diagnostic methods that would allow to fully verify these processes and evaluate the effectiveness of medical interventions.

scholarly journals Molecular Mechanisms Underlying Accelerated Aging by Defects in the FGF23-Klotho System

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Makoto Kuro-o
Keyword(s):  
Molecular Mechanisms ◽  
Accelerated Aging ◽  
Basic Research ◽  
Cellular Level ◽  
Premature Aging ◽  
Health Span ◽  
Aging Society ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Premature Aging Syndrome

The basic research of aging has been primarily focused on elucidating mechanisms of aging and longevity that are evolutionarily conserved from yeasts to primates. Such efforts have culminated in the notion that (1) senescence at the cellular level is associated with aging at the organismal level and that (2) calorie restriction and growth suppression decelerate aging. However, these important findings in the basic research have not necessarily been linked to improvement of daily medical practice in the aging society. It has become increasingly important to investigate mechanisms of aging unique to mammals or humans and apply the research fruits for the treatment of major age-related disorders to extend the health span. Seminal studies on the klotho mouse, a mutant exhibiting a premature aging syndrome, have identified phosphate as a proaging factor in mammals. In this review, mechanisms of phosphate-induced premature aging and potential therapeutic targets will be discussed, which may be directly applicable for developing novel strategies for the treatment of chronic kidney disease and its complications.

scholarly journals Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging

Biomolecules ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 882 ◽  
Author(s):  
Rashmi Dahiya ◽  
Taj Mohammad ◽  
Mohamed F. Alajmi ◽  
Md. Tabish Rehman ◽  
Gulam Mustafa Hasan ◽  
...  
Keyword(s):  
Aging Process ◽  
Molecular Mechanisms ◽  
Model Organism ◽  
Cellular Functions ◽  
Aging Research ◽  
Yeast Saccharomyces Cerevisiae ◽  
Age Related ◽  
Evolutionarily Conserved ◽  
Yeast Aging ◽  
Key Pathways

Aging represents a significant biological process having strong associations with cancer, diabetes, and neurodegenerative and cardiovascular disorders, which leads to progressive loss of cellular functions and viability. Astonishingly, age-related disorders share several genetic and molecular mechanisms with the normal aging process. Over the last three decades, budding yeast Saccharomyces cerevisiae has emerged as a powerful yet simple model organism for aging research. Genetic approaches using yeast RLS have led to the identification of hundreds of genes impacting lifespan in higher eukaryotes. Numerous interventions to extend yeast lifespan showed an analogous outcome in multi-cellular eukaryotes like fruit flies, nematodes, rodents, and humans. We collected and analyzed a multitude of observations from published literature and provide the contribution of yeast in the understanding of aging hallmarks most applicable to humans. Here, we discuss key pathways and molecular mechanisms that underpin the evolutionarily conserved aging process and summarize the current understanding and clinical applicability of its trajectories. Gathering critical information on aging biology would pave the way for future investigation targeted at the discovery of aging interventions.

scholarly journals LINKING VISUAL-SOMATOSENSORY INTEGRATION TO COGNITIVE AND MOTOR OUTCOMES IN AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S469-S469
Author(s):  
Jeannette R Mahoney
Keyword(s):  
Aging Process ◽  
Multisensory Processing ◽  
Functional Decline ◽  
Daily Functioning ◽  
Younger Adults ◽  
Gait Performance ◽  
Future Studies ◽  
Age Related ◽  
Motor Outcomes ◽  
Age Related Changes

Abstract Ability to successfully integrate simultaneous information relayed across multiple sensory systems is an integral aspect of daily functioning. Unisensory impairments have been individually linked to slower gait, functional decline, and increased risks for falls in aging. Yet, research investigating age-related changes in multisensory integration (MSI) processes still remains relatively scarce. To date, there has been converging evidence for larger behavioral multisensory effects in older compared to younger adults; however, the question of whether larger effects are actually beneficial remains largely unanswered. Findings from our studies provide support for differential multisensory processing in aging, where decreased magnitude of visual-somatosensory integration was associated with worse balance, increased falls, and slower gait. Furthermore, we established a link between visual-somatosensory integration and cognition in aging. That is, magnitude of visual-somatosensory integration was largest in older adults with normal cognitive functioning, and presence of MCI/dementia significantly decreased magnitude of visual-somatosensory integration which in turn adversely impacted balance and gait performance. While the effect of MSI has been attributed to basic degenerative changes in neuronal architecture during the aging process, this speculative interpretation has yet to be formally tested. Future studies are clearly needed to establish the structural and functional correlates of MSI in aging, specifically visual-somatosensory integration, in order to further establish the link between differential multisensory effects with other important age-related clinical outcomes. Nevertheless, these studies stress the importance of successful MSI in aging, and highlight the need for multisensory based interventions that could potentially ameliorate disability.

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