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

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1194 ◽  
Author(s):  
Dae-Sung Hwangbo ◽  
Hye-Yeon Lee ◽  
Leen Suleiman Abozaid ◽  
Kyung-Jin Min
Keyword(s):  
Molecular Mechanisms ◽  
Systems Approach ◽  
Model Organisms ◽  
Pharmacological Intervention ◽  
Calorie Intake ◽  
Intermittent Fasting ◽  
Dietary Interventions ◽  
Pharmacological Interventions ◽  
History Of ◽  
Genetic Interventions

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.

scholarly journals Longevity: epigenetic and biomolecular aspects

2015 ◽  
Vol 6 (2) ◽  
pp. 105-117 ◽  
Author(s):  
Giusi Taormina ◽  
Mario G. Mirisola
Keyword(s):  
Simple Model ◽  
Molecular Mechanisms ◽  
Model Organisms ◽  
Intermittent Fasting ◽  
Epigenetic Mechanisms ◽  
Long Term Effects ◽  
Dietary Interventions ◽  
Aging Theories

AbstractMany aging theories and their related molecular mechanisms have been proposed. Simple model organisms such as yeasts, worms, fruit flies and others have massively contributed to their clarification, and many genes and pathways have been associated with longevity regulation. Among them, insulin/IGF-1 plays a key and evolutionary conserved role. Interestingly, dietary interventions can modulate this pathway. Calorie restriction (CR), intermittent fasting, and protein and amino acid restriction prolong the lifespan of mammals by IGF-1 regulation. However, some recent findings support the hypothesis that the long-term effects of diet also involve epigenetic mechanisms. In this review, we describe the best characterized aging pathways and highlight the role of epigenetics in diet-mediated longevity.

scholarly journals Managing the Oocyte Meiotic Arrest—Lessons from Frogs and Jellyfish

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1150 ◽  
Author(s):  
Catherine Jessus ◽  
Catriona Munro ◽  
Evelyn Houliston
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polar Body ◽  
Model Organisms ◽  
Oocyte Growth ◽  
M Phase ◽  
History Of ◽  
Enormous Variation ◽  
Polar Body Formation ◽  
Reliable Mechanism

During oocyte development, meiosis arrests in prophase of the first division for a remarkably prolonged period firstly during oocyte growth, and then when awaiting the appropriate hormonal signals for egg release. This prophase arrest is finally unlocked when locally produced maturation initiation hormones (MIHs) trigger entry into M-phase. Here, we assess the current knowledge of the successive cellular and molecular mechanisms responsible for keeping meiotic progression on hold. We focus on two model organisms, the amphibian Xenopus laevis, and the hydrozoan jellyfish Clytia hemisphaerica. Conserved mechanisms govern the initial meiotic programme of the oocyte prior to oocyte growth and also, much later, the onset of mitotic divisions, via activation of two key kinase systems: Cdk1-Cyclin B/Gwl (MPF) for M-phase activation and Mos-MAPkinase to orchestrate polar body formation and cytostatic (CSF) arrest. In contrast, maintenance of the prophase state of the fully-grown oocyte is assured by highly specific mechanisms, reflecting enormous variation between species in MIHs, MIH receptors and their immediate downstream signalling response. Convergence of multiple signalling pathway components to promote MPF activation in some oocytes, including Xenopus, is likely a heritage of the complex evolutionary history of spawning regulation, but also helps ensure a robust and reliable mechanism for gamete production.

scholarly journals The landscape of longevity across phylogeny

2020 ◽  
Author(s):  
Dmitriy I. Podolskiy ◽  
Andrei Avanesov ◽  
Alexander Tyshkovskiy ◽  
Emily Porter ◽  
Michael Petrascheck ◽  
...  
Keyword(s):  
Fiber Bundle ◽  
Distribution Functions ◽  
Model Organisms ◽  
Dietary Interventions ◽  
Pharmacological Interventions ◽  
Survival Curves ◽  
Distinct Structure ◽  
Age Dependent ◽  
Lifespan Distribution ◽  
Dependent Mortality

AbstractLifespan of model organisms can be extended by genetic, dietary and pharmacological interventions, but these effects may be negated by other factors. To understand robustness of longevity interventions within and across species, we analyzed age-dependent mortality of yeast, fruit flies, nematodes and mice subjected to thousands of genetic, pharmacological or dietary interventions, and applied the principles learned to other organisms. Across phylogeny, the accessible space of lifespan distribution functions, the “landscape of longevity”, has a distinct structure of a fiber bundle, with individual fibers given by Strehler-Mildvan degeneracy manifolds. Within species, most interventions perturb parameters of survival curves along particular degeneracy manifolds. Transitions across manifolds are difficult to achieve, but they may lead to robust lifespan-modulating effects. Analyses of intraspecific degeneracy manifolds revealed soft bounds on achievable longevity. For humans, this bound is ∼138 years.

scholarly journals Combined intermittent fasting and ERK inhibition enhance the anti-tumor effects of chemotherapy via the GSK3β-SIRT7 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaolong Tang ◽  
Guo Li ◽  
Lei Shi ◽  
Fengting Su ◽  
Minxian Qian ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Glycogen Synthase ◽  
E3 Ligase ◽  
Glucose Deprivation ◽  
Mek Inhibitor ◽  
Intermittent Fasting ◽  
Cancer Therapies ◽  
Dietary Interventions ◽  
The Face ◽  
Subsequent Activation

AbstractDietary interventions such as intermittent fasting (IF) have emerged as an attractive strategy for cancer therapies; therefore, understanding the underlying molecular mechanisms is pivotal. Here, we find SIRT7 decline markedly attenuates the anti-tumor effect of IF. Mechanistically, AMP-activated protein kinase (AMPK) phosphorylating SIRT7 at T263 triggers further phosphorylation at T255/S259 by glycogen synthase kinase 3β (GSK3β), which stabilizes SIRT7 by decoupling E3 ligase UBR5. SIRT7 hyperphosphorylation achieves anti-tumor activity by disrupting the SKP2-SCF E3 ligase, thus preventing SKP2-mediated K63-linked AKT polyubiquitination and subsequent activation. In contrast, GSK3β-SIRT7 axis is inhibited by EGF/ERK2 signaling, with ERK2 inactivating GSK3β, thus accelerating SIRT7 degradation. Unfavorably, glucose deprivation or chemotherapy hijacks the GSK3β-SIRT7 axis via ERK2, thus activating AKT and ensuring survival. Notably, Trametinib, an FDA-approved MEK inhibitor, enhances the efficacy of combination therapy with doxorubicin and IF. Overall, we have revealed the GSK3β-SIRT7 axis that must be fine-tuned in the face of the energetic and oncogenic stresses in malignancy.

scholarly journals Metabolic Regulation of Stem Cells in Aging

2021 ◽  
Author(s):  
Andrea Keller ◽  
Tyus Temple ◽  
Behnam Sayanjali ◽  
Maria M. Mihaylova
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Dietary Restriction ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
The Body ◽  
Model Organisms ◽  
Dietary Interventions

AbstractPurpose of ReviewFrom invertebrates to vertebrates, the ability to sense nutrient availability is critical for survival. Complex organisms have evolved numerous signaling pathways to sense nutrients and dietary fluctuations, which influence many cellular processes. Although both overabundance and extreme depletion of nutrients can lead to deleterious effects, dietary restriction without malnutrition can increase lifespan and promote overall health in many model organisms. In this review, we focus on age-dependent changes in stem cell metabolism and dietary interventions used to modulate stem cell function in aging.Recent FindingsOver the last half-century, seminal studies have illustrated that dietary restriction confers beneficial effects on longevity in many model organisms. Many researchers have now turned to dissecting the molecular mechanisms by which these diets affect aging at the cellular level. One subpopulation of cells of particular interest are adult stem cells, the most regenerative cells of the body. It is generally accepted that the regenerative capacity of stem cells declines with age, and while the metabolic requirements of each vary across tissues, the ability of dietary interventions to influence stem cell function is striking.SummaryIn this review, we will focus primarily on how metabolism plays a role in adult stem cell homeostasis with respect to aging, with particular emphasis on intestinal stem cells while also touching on hematopoietic, skeletal muscle, and neural stem cells. We will also discuss key metabolic signaling pathways influenced by both dietary restriction and the aging process, and will examine their role in improving tissue homeostasis and lifespan. Understanding the mechanisms behind the metabolic needs of stem cells will help bridge the divide between a basic science interpretation of stem cell function and a whole-organism view of nutrition, thereby providing insight into potential dietary or therapeutic interventions.

A Dynamic Systems Approach to Personality

2001 ◽  
Vol 6 (3) ◽  
pp. 172-176 ◽  
Author(s):  
Lawrence A. Pervin
Keyword(s):  
Dynamic Systems ◽  
Systems Approach ◽  
Biological Processes ◽  
Recent Advances ◽  
Dynamic View ◽  
The Future ◽  
History Of

David Magnusson has been the most articulate spokesperson for a holistic, systems approach to personality. This paper considers three concepts relevant to a dynamic systems approach to personality: dynamics, systems, and levels. Some of the history of a dynamic view is traced, leading to an emphasis on the need for stressing the interplay among goals. Concepts such as multidetermination, equipotentiality, and equifinality are shown to be important aspects of a systems approach. Finally, attention is drawn to the question of levels of description, analysis, and explanation in a theory of personality. The importance of the issue is emphasized in relation to recent advances in our understanding of biological processes. Integrating such advances into a theory of personality while avoiding the danger of reductionism is a challenge for the future.

Effects of Diets on Adipose Tissue

2019 ◽  
Vol 26 (19) ◽  
pp. 3593-3612
Author(s):  
Silvia Ezquerro ◽  
Amaia Rodríguez ◽  
Piero Portincasa ◽  
Gema Frühbeck
Keyword(s):  
Adipose Tissue ◽  
Food Preferences ◽  
Overweight And Obesity ◽  
Economic Consequences ◽  
Present Review ◽  
Calorie Intake ◽  
Dietary Interventions ◽  
Major Health Problem ◽  
Global Epidemic ◽  
Excess Adiposity

Background: Obesity is a major health problem that has become a global epidemic. Overweight and obesity are commonly associated with the development of several pathologies, such as insulin resistance, cardiovascular diseases, sleep apnea and several types of cancer, which can lead to further morbidity and mortality. An increased abdominal adiposity renders overweight and obese individuals more prone to metabolic and cardiovascular problems. Objective: This Review aims to describe the dietary strategies to deal with excess adiposity given the medical, social and economic consequences of obesity. Methods: One hundred and eighty-five papers were included in the present Review. Results: Excess adiposity leads to several changes in the biology, morphology and function of the adipose tissue, such as adipocyte hypertrophy and hyperplasia, adipose tissue inflammation and fibrosis and an impaired secretion of adipokines, contributing to the onset of obesity- related comorbidities. The first approach for obesity management and prevention is the implementation of a diet combined with physical activity. The present review summarizes the compelling evidence showing body composition changes, impact on cardiometabolism and potential adverse effects of very-low calorie, low- and high-carbohydrate, high-protein or low-fat diets. The use of macronutrients during the preprandial and postprandial state has been also reviewed to better understand the metabolic changes induced by different dietary interventions. Conclusion: Dietary changes should be individualised, tailored to food preferences and allow for flexible approaches to reducing calorie intake in order to increase the motivation and compliance of overweight and obese patients.

Novel Pharmacotherapeutics for Stress-Related Disorders

2019 ◽  
pp. 642-672
Author(s):  
Jamie E. Mondello ◽  
Jenny E. Pak ◽  
Dennis F. Lovelock ◽  
Terrence Deak
Keyword(s):  
Mental Health Problems ◽  
Drug Efficacy ◽  
Careful Consideration ◽  
Pharmacological Intervention ◽  
Pharmacological Interventions ◽  
Diverse Range ◽  
Disease States ◽  
Efficacy Trials ◽  
Participant Selection ◽  
The Relationship

Most mental health problems associated with psychological distress originate with activation of centrally regulated stress pathways, yet a diverse range of central nervous system and somatic disease states can be influenced by exposure to severe or unrelenting stress. The goal of this chapter is to provide a conceptual framework to guide the development of pharmacological intervention strategies. We propose that careful consideration of the relationship between the timing of stressful life experiences, pharmacological intervention, and the ultimate expression of disease symptomatology is critical for the development of pharmacological interventions to treat stress-related disorders. We review a range of physiological systems that are known to be activated by stress, offering potentially new targets for drug development efforts, and argue that participant selection is a key predictor of drug efficacy trials. In doing so, we point toward inflammatory signaling pathways as a potential final common mediator of multiple stress-related disease states.

scholarly journals The Senescence-Associated Secretory Phenotype (SASP) in the Challenging Future of Cancer Therapy and Age-Related Diseases

Biology ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 485
Author(s):  
Lorenzo Cuollo ◽  
Fabrizio Antonangeli ◽  
Angela Santoni ◽  
Alessandra Soriani
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Therapeutic Strategies ◽  
Senescent Cell ◽  
Pharmacological Intervention ◽  
Tissue Microenvironment ◽  
Age Related ◽  
Secretory Phenotype ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Cellular senescence represents a robust tumor-protecting mechanism that halts the proliferation of stressed or premalignant cells. However, this state of stable proliferative arrest is accompanied by the Senescence-Associated Secretory Phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment and contributes to age-related conditions, including, paradoxically, cancer. Novel therapeutic strategies aim at eliminating senescent cells with the use of senolytics or abolishing the SASP without killing the senescent cell with the use of the so-called “senomorphics”. In addition, recent works demonstrate the possibility of modifying the composition of the secretome by genetic or pharmacological intervention. The purpose is not to renounce the potent immunostimulatory nature of SASP, but rather learning to modulate it for combating cancer and other age-related diseases. This review describes the main molecular mechanisms regulating the SASP and reports the evidence of the feasibility of abrogating or modulating the SASP, discussing the possible implications of both strategies.

scholarly journals Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner

GeroScience ◽  
2021 ◽  
Author(s):  
Yoko O. Henderson ◽  
Nazmin Bithi ◽  
Christopher Link ◽  
Jie Yang ◽  
Rebecca Schugar ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Dietary Intervention ◽  
Caloric Intake ◽  
Production Capacity ◽  
Late Life ◽  
Model Organisms ◽  
Intermittent Fasting ◽  
Sexually Dimorphic ◽  
Average Life Expectancy ◽  
Multiple Components

AbstractGlobal average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan. However, DR is not widely implemented in the clinic due to patient compliance and its lack of mechanistic underpinnings. Thus, the present study tested the effects of a somewhat more clinically applicable and adoptable DR regimen, every-other-day (EOD) intermittent fasting, on frailty in 20-month-old male and female C57BL/6 mice. Frailty was determined by a series of metabolic, musculoskeletal, and cognitive tasks performed prior to and toward the end of the 2.5-month dietary intervention. Late-life EOD fasting attenuated overall energy intake, hypothalamic inflammatory gene expression, and frailty in males. However, it failed to reduce overall caloric intake and had a little positive effect in females. Given that the selected benefits of DR are dependent on augmented production of the gasotransmitter hydrogen sulfide (H2S) and that renal H2S production declines with age, we tested the effects of EOD fasting on renal H2S production capacity and its connection to frailty in males. EOD fasting boosted renal H2S production, which positively correlated with improvements in multiple components of frailty tasks. Therefore, late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the effects of late-life EOD fasting on frailty.

Sign in / Sign up

Export Citation Format

Share Document