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https://www.readbyqxmd.com/read/28108330/pleiotropic-responses-to-methionine-restriction
#1
Gene Ables, Jay Johnson
Methionine restriction (MR) extends lifespan across different species. The main responses of rodent models to MR are well-documented in adipose tissue (AT) and liver, which have reduced mass and improved insulin sensitivity, respectively. Recently, molecular mechanisms that improve healthspan have been identified in both organs during MR. In fat, MR induced a futile lipid cycle concomitant with beige AT accumulation, producing elevated energy expenditure. In liver, MR upregulated fibroblast growth factor 21 and improved glucose metabolism in aged mice and in response to a high-fat diet...
January 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28049008/the-gut-microbiota-of-centenarians-signatures-of-longevity-in-the-gut-microbiota-profile
#2
REVIEW
Biagi Elena, Simone Rampelli, Silvia Turroni, Sara Quercia, Marco Candela, Patrizia Brigidi
The changing physiology and lifestyle of elderly people affect the gut microbiota composition, the changes of which can, in turn, affect the health maintenance of the ageing host. In a co-evolutionary vision of the relationship between gut microbiota and ageing as an adaptive process of the human superorganism, long-living individuals who get to "successfully" age might be the ones whose microbiota manages to continuously re-establish a mutualistic relationship with the host, adapting to the progressive endogenous and environmental changes...
December 31, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28035757/papp-a-a-promising-therapeutic-target-for-healthy-longevity
#3
REVIEW
Cheryl A Conover, Claus Oxvig
Pregnancy-associated plasma protein-A (PAPP-A) is a proteolytic enzyme that was discovered to increase local insulin-like growth factor (IGF) availability for receptor activation through cleavage of inhibitory IGF binding proteins (IGFBPs). Reduced IGF signaling has been associated with increased lifespan and healthspan. Therefore, inhibition of PAPP-A represents a novel approach to indirectly decrease the availability of bioactive IGF. Here, we will review data in support of PAPP-A as a therapeutic target to promote healthy longevity...
December 29, 2016: Aging Cell
https://www.readbyqxmd.com/read/28035340/targeting-glucose-metabolism-for-healthy-aging
#4
REVIEW
Rachel A Brewer, Victoria K Gibbs, Daniel L Smith
Advancing age is the greatest single risk factor for numerous chronic diseases. Thus, the ability to target the aging process can facilitate improved healthspan and potentially lifespan. Lack of adequate glucoregulatory control remains a recurrent theme accompanying aging and chronic disease, while numerous longevity interventions result in maintenance of glucoregulatory control. In this review, we propose targeting glucose metabolism to enhance regulatory control as a means to ameliorate the aging process...
October 27, 2016: Nutr Healthy Aging
https://www.readbyqxmd.com/read/28034832/proteasome-activation-enhances-stemness-and-lifespan-of-human-mesenchymal-stem-cells
#5
Marianna Kapetanou, Niki Chondrogianni, Spyros Petrakis, George Koliakos, Efstathios S Gonos
The age-associated decline of adult stem cell function contributes to the physiological failure of homeostasis during aging. The proteasome plays a key role in the maintenance of proteostasis and its failure is associated with various biological phenomena including senescence and aging. Although stem cell biology has attracted intense attention, the role of proteasome in stemness and its age-dependent deterioration remains largely unclear. By employing both Wharton's-Jelly- and Adipose-derived human adult mesenchymal stem cells (hMSCs), we reveal a significant age-related decline in proteasome content and peptidase activities, accompanied by alterations of proteasomal complexes...
December 27, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27986499/targeting-chromatin-aging-the-epigenetic-impact-of-longevity-associated-interventions
#6
Adam E Field, Peter D Adams
A rapidly growing body of evidence has shown that chromatin undergoes radical alterations as an organism ages, but how these changes relate to aging itself is an open question. It is likely that these processes contribute to genomic instability and loss of transcriptional fidelity, which in turn drives deleterious age-related phenotypes. Interventions associated with increased healthspan and longevity such as reduced insulin/IGF signalling (IIS), inhibition of mTOR and energy depletion resulting in SIRT1/AMPK activation, all have beneficial effects which ameliorate multiple facets of age-associated decline...
December 13, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27935214/stabilized-sulforaphane-for-clinical-use-phytochemical-delivery-efficiency
#7
Jed W Fahey, Kristina L Wade, Scott L Wehage, W David Holtzclaw, Hua Liu, Paul Talalay, Edward Fuchs, Katherine K Stephenson
SCOPE: The isothiocyanate sulforaphane (SF) from broccoli, is one of the most potent known inducers of the cytoprotective phase 2 response. Its role in a host of biochemical pathways make it a major component of plant-based protective strategies for enhancing healthspan. Many nutritional supplements are now marketed that purport to contain SF, which in plants exists as a stable precursor, a thioglucoside hydroxysulfate. However, SF in pure form must be stabilized for use in supplements...
December 9, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27921031/amniotic-epithelial-cells-a-new-tool-to-combat-aging-and-age-related-diseases
#8
Clara Di Germanio, Michel Bernier, Rafael de Cabo, Barbara Barboni
The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27884780/regulation-of-metabolic-health-and-aging-by-nutrient-sensitive-signaling-pathways
#9
Nicole E Cummings, Dudley W Lamming
All organisms need to be capable of adapting to changes in the availability and composition of nutrients. Over 75 years ago, researchers discovered that a calorie restricted (CR) diet could significantly extend the lifespan of rats, and since then a CR diet has been shown to increase lifespan and healthspan in model organisms ranging from yeast to non-human primates. In this review, we discuss the effects of a CR diet on metabolism and healthspan, and highlight emerging evidence that suggests that dietary composition - the precise macronutrients that compose the diet - may be just as important as caloric content...
November 22, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27881168/loss-of-porin-function-in-dopaminergic-neurons-of-drosophila-is-suppressed-by-buffy
#10
P Githure M'Angale, Brian E Staveley
BACKGROUND: Mitochondrial porin, also known as the voltage-dependent anion channel (VDAC), is a multi-functional channel protein that shuttles metabolites between the mitochondria and the cytosol and implicated in cellular life and death decisions. The inhibition of porin under the control of neuronal Ddc-Gal4 result in short lifespan and in an age-dependent loss in locomotor function, phenotypes that are strongly associated with Drosophila models of Parkinson disease. METHODS: Loss of porin function was achieved through exploitation of RNA interference while derivative lines were generated by homologous recombination and tested by PCR...
November 24, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27828773/implementation-of-the-ymca-diabetes-prevention-program-throughout-an-integrated-health-system-a-translational-study
#11
Ron Adams, Christopher J Hebert, Linda Mcvey, Roger Williams
CONTEXT: HealthSpan Physicians (HSP), an integrated medical system in Northeast Ohio, partnered with the Young Men's Christian Association (YMCA) of Greater Cleveland to implement a referral system for the evidence-based Diabetes Prevention Program (DPP) throughout HSP. The YMCA of USA employs a cost-effective, customized version of the original DPP in which coaches take the place of in-house clinical staff. Efficacy of the YMCA DPP was shown earlier in the DEPLOY Study. OBJECTIVE: To improve outcomes of metrics used in the DEPLOY Study...
2016: Permanente Journal
https://www.readbyqxmd.com/read/27808406/declining-performance-of-master-athletes-silhouettes-of-the-trajectory-of-healthy-human-ageing
#12
Norman R Lazarus, Stephen D R Harridge
Analysis of world record performances by master athletes suggests an essentially linear decline with age until around the eighth decade after which performance decline accelerates. Because these records are obtained from highly trained individuals they can be viewed as being reflective of the diminution of integrative physiological prowess that occurs solely as a result of ageing, unaffected by the confounding effects of inactivity. It can also be argued that these performance profiles mirror and provide an insight into the trajectory of the physiology of the human ageing process...
November 3, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27790247/pleiotropic-meta-analyses-of-longitudinal-studies-discover-novel-genetic-variants-associated-with-age-related-diseases
#13
Liang He, Yelena Kernogitski, Irina Kulminskaya, Yury Loika, Konstantin G Arbeev, Elena Loiko, Olivia Bagley, Matt Duan, Arseniy Yashkin, Svetlana V Ukraintseva, Mikhail Kovtun, Anatoliy I Yashin, Alexander M Kulminski
Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27777382/prenatal-hyperbaric-normoxia-treatment-improves-healthspan-and-regulates-chitin-metabolic-genes-in-drosophila-melanogaster
#14
Suyeun Yu, Eunil Lee, Bodokhsuren Tsogbadrakh, Gwang-Ic Son, Mari Kim
Aging is a universal, irreversible process accompanied by physiological declines that culminate in death. Rapid progress in gerontology research has revealed that aging can be slowed through mild stress-induced hormesis. We previously reported that hyperbaric normoxia (HN, 2 atm absolute pressure with 10% O2) induces a cytoprotective response in vitro by regulating fibronectin. In the present study, we investigated the hormetic effects of prenatal HN exposure on Drosophila healthspan related to molecular defense mechanisms...
October 24, 2016: Aging
https://www.readbyqxmd.com/read/27746329/in%C3%A2-vivo-and-in%C3%A2-vitro-evaluation-for-nutraceutical-purposes-of%C3%A2-capsaicin-%C3%A2-capsanthin-lutein-and-four-pepper-varieties
#15
Zahira Fernández-Bedmar, Angeles Alonso-Moraga
: The purpose of this study is to determine the nutraceutic potential of different Capsicum sp, capsaicin, capsanthin and lutein and provide data in order to clarify the conflicting results obtained for capsaicin by different authors. To achieve these objectives, in vivo (geno/antigenotoxicity and lifespan assays in the animal model Drosophila) and in vitro (cytotoxicity and DNA-fragmentation assays in HL60 promyelocytic cell line) assays were carried out. Results showed that i) none of the tested substances were genotoxic except green hot pepper and capsaicin at the highest tested concentration (5 mg/mL and 11...
December 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27732836/nad-replenishment-improves-lifespan-and-healthspan-in-ataxia-telangiectasia-models-via-mitophagy-and-dna-repair
#16
Evandro Fei Fang, Henok Kassahun, Deborah L Croteau, Morten Scheibye-Knudsen, Krisztina Marosi, Huiming Lu, Raghavendra A Shamanna, Sumana Kalyanasundaram, Ravi Chand Bollineni, Mark A Wilson, Wendy B Iser, Bradley N Wollman, Marya Morevati, Jun Li, Jesse S Kerr, Qiping Lu, Tyler B Waltz, Jane Tian, David A Sinclair, Mark P Mattson, Hilde Nilsen, Vilhelm A Bohr
Ataxia telangiectasia (A-T) is a rare autosomal recessive disease characterized by progressive neurodegeneration and cerebellar ataxia. A-T is causally linked to defects in ATM, a master regulator of the response to and repair of DNA double-strand breaks. The molecular basis of cerebellar atrophy and neurodegeneration in A-T patients is unclear. Here we report and examine the significance of increased PARylation, low NAD(+), and mitochondrial dysfunction in ATM-deficient neurons, mice, and worms. Treatments that replenish intracellular NAD(+) reduce the severity of A-T neuropathology, normalize neuromuscular function, delay memory loss, and extend lifespan in both animal models...
October 11, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27721062/molecular-pathology-endpoints-useful-for-aging-studies
#17
L J Niedernhofer, J L Kirkland, W Ladiges
The first clinical trial aimed at targeting fundamental processes of aging will soon be launched (TAME: Targeting Aging with Metformin). In its wake is a robust pipeline of therapeutic interventions that have been demonstrated to extend lifespan or healthspan of preclinical models, including rapalogs, antioxidants, anti-inflammatory agents, and senolytics. This ensures that if the TAME trial is successful, numerous additional clinical trials are apt to follow. But a significant impediment to these trials remains the question of what endpoints should be measured? The design of the TAME trial very cleverly skirts around this based on the fact that there are decades of data on metformin in humans, providing unequaled clarity of what endpoints are most likely to yield a positive outcome...
October 6, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27705904/a-cross-sectional-study-of-male-and-female-c57bl-6nia-mice-suggests-lifespan-and-healthspan-are-not-necessarily-correlated
#18
Kathleen E Fischer, Jessica M Hoffman, Lauren B Sloane, Jonathan A L Gelfond, Vanessa Y Soto, Arlan G Richardson, Steven N Austad
Lifespan provides a discrete metric that is intuitively appealing and the assumption has been that healthspan is extended concomitant with lifespan. Medicine has been more successful at extending life than preserving health during aging. Interventions that extend lifespan in model organisms do not always result in a corresponding increase in healthspan, suggesting that lifespan and healthspan may be uncoupled. To understand how interventions that extend life affect healthspan, we need measures that distinguish between young and old animals...
October 2, 2016: Aging
https://www.readbyqxmd.com/read/27683205/uncoupling-associations-of-risk-alleles-with-endophenotypes-and-phenotypes-insights-from-the-apob-locus-and-heart-related-traits
#19
Alexander M Kulminski, Yelena Kernogitski, Irina Culminskaya, Yury Loika, Konstantin G Arbeev, Olivia Bagley, Matt Duan, Liubov Arbeeva, Svetlana V Ukraintseva, Deqing Wu, Eric Stallard, Anatoliy I Yashin
Traditionally, genomewide association studies (GWAS) have emphasized the benefits of large samples in the analyses of age-related traits rather than their specific properties. We adopted a realistic concept of genetic susceptibility to inherently heterogeneous, age-related traits driven by the elusive role of evolution in their properties. We analyzed in detail the associations of rs693 and rs562338 polymorphisms representing the Apolipoprotein B locus with endophenotypes (total cholesterol [TC] and high-density lipoprotein cholesterol) and phenotypes (myocardial infarction [MI] and survival) in four large-scale studies, which include 20 748 individuals with 2357 MI events...
September 28, 2016: Aging Cell
https://www.readbyqxmd.com/read/27671971/effect-of-glycation-inhibitors-on-aging-and-age-related-diseases
#20
REVIEW
Izabela Sadowska-Bartosz, Grzegorz Bartosz
Vast evidence supports the view that glycation of proteins is one of the main factors contributing to aging and is an important element of etiopathology of age-related diseases, especially type 2 diabetes mellitus, cataract and neurodegenerative diseases. Counteracting glycation can therefore be a means of increasing both the lifespan and healthspan. In this review, accumulation of glycation products during aging is presented, pathophysiological effects of glycation are discussed and ways of attenuation of the effects of glycation are described, concentrating on prevention of glycation...
September 23, 2016: Mechanisms of Ageing and Development
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