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 A novel approach to assess the dynamics of extra-chromosomal circular ribosomal DNA in human cells

2014 ◽  
Author(s):  
Joerg R Leheste ◽  
Emily Forbes ◽  
Kristin DiGregorio ◽  
Victoria Katz ◽  
Alyssa Miceli ◽  
...  
Keyword(s):  
Life Span ◽  
Signaling Pathways ◽  
Ribosomal Dna ◽  
Experimental Manipulation ◽  
Human Cells ◽  
Model Organisms ◽  
Age Related ◽  
Novel Approach ◽  
Extend Life Span ◽  
Nutrient Signaling

Several nutrient-signaling pathways that extend life span have been described in model organisms. Thus, parallel and redundant signaling pathways that are similar across species might be subject to experimental manipulation. Here, we develop a PCR-based technique for testing the hypothesis that mitotic accumulation of extra-chromosomal ribosomal DNA circles might also determine life span in human cells. Using resveratrol, a phytochemical that counters age-related signs, we find treatment-dependent subcellular accumulations of extra-chromosomal 5S ribosomal DNA in human cell lines. These data suggest an association between DNA circles and intrinsic aging and demonstrate the utility of a PCR-based technique for studying the accumulation of dysfunctional molecules that promote senescence.

scholarly journals A novel approach to assess the dynamics of extra-chromosomal circular ribosomal DNA in human cells

2014 ◽  
Author(s):  
Joerg R Leheste ◽  
Emily Forbes ◽  
Kristin DiGregorio ◽  
Victoria Katz ◽  
Alyssa Miceli ◽  
...  
Keyword(s):  
Life Span ◽  
Signaling Pathways ◽  
Ribosomal Dna ◽  
Experimental Manipulation ◽  
Human Cells ◽  
Model Organisms ◽  
Age Related ◽  
Novel Approach ◽  
Extend Life Span ◽  
Nutrient Signaling

Several nutrient-signaling pathways that extend life span have been described in model organisms. Thus, parallel and redundant signaling pathways that are similar across species might be subject to experimental manipulation. Here, we develop a PCR-based technique for testing the hypothesis that mitotic accumulation of extra-chromosomal ribosomal DNA circles might also determine life span in human cells. Using resveratrol, a phytochemical that counters age-related signs, we find treatment-dependent subcellular accumulations of extra-chromosomal 5S ribosomal DNA in human cell lines. These data suggest an association between DNA circles and intrinsic aging and demonstrate the utility of a PCR-based technique for studying the accumulation of dysfunctional molecules that promote senescence.

scholarly journals The Gut Microbiota and Healthy Aging: A Mini-Review

Gerontology ◽  
2018 ◽  
Vol 64 (6) ◽  
pp. 513-520 ◽  
Author(s):  
Sangkyu Kim ◽  
S. Michal Jazwinski
Keyword(s):  
Gut Microbiota ◽  
Individual Variation ◽  
Gut Microbiome ◽  
Chronological Age ◽  
Low Grade ◽  
Beneficial Effects ◽  
Gut Dysbiosis ◽  
Age Related ◽  
Host Health ◽  
Nutrient Signaling

The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.

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 Shedding Light on the Effects of Calorie Restriction and Its Mimetics on Skin Biology

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1529 ◽  
Author(s):  
Yeon Ja Choi
Keyword(s):  
Calorie Restriction ◽  
Skin Diseases ◽  
Skin Aging ◽  
Peroxisome Proliferator ◽  
Extrinsic Factors ◽  
Inflammatory Skin Diseases ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
Age Related ◽  
Skin Biology

During the aging process of an organism, the skin gradually loses its structural and functional characteristics. The skin becomes more fragile and vulnerable to damage, which may contribute to age-related diseases and even death. Skin aging is aggravated by the fact that the skin is in direct contact with extrinsic factors, such as ultraviolet irradiation. While calorie restriction (CR) is the most effective intervention to extend the lifespan of organisms and prevent age-related disorders, its effects on cutaneous aging and disorders are poorly understood. This review discusses the effects of CR and its alternative dietary intake on skin biology, with a focus on skin aging. CR structurally and functionally affects most of the skin and has been reported to rescue both age-related and photo-induced changes. The anti-inflammatory, anti-oxidative, stem cell maintenance, and metabolic activities of CR contribute to its beneficial effects on the skin. To the best of the author’s knowledge, the effects of fasting or a specific nutrient-restricted diet on skin aging have not been evaluated; these strategies offer benefits in wound healing and inflammatory skin diseases. In addition, well-known CR mimetics, including resveratrol, metformin, rapamycin, and peroxisome proliferator-activated receptor agonists, show CR-like prevention against skin aging. An overview of the role of CR in skin biology will provide valuable insights that would eventually lead to improvements in skin health.

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 Calorie Restriction: Is AMPK a Key Sensor and Effector?

Physiology ◽  
2011 ◽  
Vol 26 (4) ◽  
pp. 214-224 ◽  
Author(s):  
Carles Cantó ◽  
Johan Auwerx
Keyword(s):  
Protein Kinase ◽  
Life Span ◽  
Calorie Restriction ◽  
Energy Availability ◽  
Beneficial Effects ◽  
Extend Life Span ◽  
Energy Sensor ◽  
External Cues ◽  
Amp Activated Protein Kinase

Dietary restriction can extend life span in most organisms tested to date, suggesting that mechanisms sensing nutrient and energy availability might regulate longevity. The AMP-activated protein kinase (AMPK) has emerged as a key energy sensor with the ability to transcriptionally reprogram the cell and metabolically adapt to external cues. In this review, we will discuss the possible role of AMPK in the beneficial effects of calorie restriction on health and life span.

scholarly journals Phosphoglycolate phosphatase homologs act as glycerol-3-phosphate phosphatase to control stress and healthspan in C. elegans

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Elite Possik ◽  
Clémence Schmitt ◽  
Anfal Al-Mass ◽  
Ying Bai ◽  
Laurence Côté ◽  
...  
Keyword(s):  
Calorie Restriction ◽  
Mammalian Cells ◽  
Healthy Aging ◽  
Model Organism ◽  
Metabolic Stress ◽  
Clinical Importance ◽  
C Elegans ◽  
Beneficial Effects ◽  
Age Related

AbstractMetabolic stress due to nutrient excess and lipid accumulation is at the root of many age-associated disorders and the identification of therapeutic targets that mimic the beneficial effects of calorie restriction has clinical importance. Here, using C. elegans as a model organism, we study the roles of a recently discovered enzyme at the heart of metabolism in mammalian cells, glycerol-3-phosphate phosphatase (G3PP) (gene name Pgp) that hydrolyzes glucose-derived glycerol-3-phosphate to glycerol. We identify three Pgp homologues in C. elegans (pgph) and demonstrate in vivo that their protein products have G3PP activity, essential for glycerol synthesis. We demonstrate that PGPH/G3PP regulates the adaptation to various stresses, in particular hyperosmolarity and glucotoxicity. Enhanced G3PP activity reduces fat accumulation, promotes healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility. Thus, PGP/G3PP can be considered as a target for age-related metabolic disorders.

scholarly journals Lisinopril Preserves Physical Resilience and Extends Life Span in a Genotype-Specific Manner in Drosophila melanogaster

2019 ◽  
Vol 74 (12) ◽  
pp. 1844-1852
Author(s):  
Mariann M Gabrawy ◽  
Sarah Campbell ◽  
Mary Anna Carbone ◽  
Tatiana V Morozova ◽  
Gunjan H Arya ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Drosophila Melanogaster ◽  
Life Span ◽  
Physical Performance ◽  
Ace Inhibitor ◽  
Transcriptome Profiling ◽  
Reference Panel ◽  
Beneficial Effects ◽  
Age Related ◽  
Inhibitor Compounds

Abstract Physical resiliency declines with age and comorbid conditions. In humans, angiotensin-converting enzyme (ACE) has been associated with attenuation of the decline in physical performance with age. ACE-inhibitor compounds, commonly prescribed for hypertension, often have beneficial effects on physical performance however the generality of these effects are unclear. Here, we tested the effects of the ACE-inhibitor Lisinopril on life span, and age-specific speed, endurance, and strength using three genotypes of the Drosophila melanogaster Genetic Reference Panel. We show that age-related decline in physical performance and survivorship varies with genetic background. Lisinopril treatment increased mean life span in all Drosophila Genetic Reference Panel lines, but its effects on life span, speed, endurance, and strength depended on genotype. We show that genotypes with increased physical performance on Lisinopril treatment experienced reduced age-related protein aggregation in muscle. Knockdown of skeletal muscle-specific Ance, the Drosophila ortholog of ACE, abolished the effects of Lisinopril on life span, implying a role for skeletal muscle Ance in survivorship. Using transcriptome profiling, we identified genes involved in stress response that showed expression changes associated with genotype and age-dependent responsiveness to Lisinopril. Our results demonstrate that Ance is involved in physical decline and demonstrate genetic variation in phenotypic responses to an ACE inhibitor.

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