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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...
October 13, 2016: Food and Chemical Toxicology
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
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
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
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
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
Albert Stuart Reece, Mervyn Rees Thomas, Amanda Norman, Gary Kenneth Hulse
Whilst disturbances of female reproductive hormones and function are commonplace in opioid dependence, their pathophysiological interrelationships are not well understood. Hormonal levels in females were compared in 77 opioid dependent patients (ODP) and 148 medical controls (MC) including 205 and 364 repeat studies. Significant changes in FSH, LH, oestradiol, testosterone and SBG were noted including power functions with age. The FSH/LH was lower in ODP (P=0.0150) and the ratio inversion point occurred at 28...
September 20, 2016: Reproductive Toxicology
Alexandra Vaccaro, Serge Birman, André Klarsfeld
Endogenous circadian clocks with ~24-h periodicity are found in most organisms from cyanobacteria to humans. Daylight synchronizes these clocks to solar time. In humans, shift-work and jet lag perturb clock synchronization, and such perturbations, when repeated or chronic, are strongly suspected to be detrimental to healthspan. Here we investigated locomotor aging and longevity in Drosophila melanogaster with genetically or environmentally disrupted clocks. We compared two mutations in period (per, a gene essential for circadian rhythmicity in Drosophila), after introducing them in a common reference genetic background: the arrhythmic per(01), and per(T) which displays robust short 16-h rhythms...
September 14, 2016: Experimental Gerontology
Francesco Bifari, Enzo Nisoli
Substantial evidences have been accumulated to suggest the positive effect of branched-chain amino acid (BCAA) supplementation or BCAA-rich diets on the regulation of body weight, muscle protein synthesis, glucose homeostasis, aging process, and healthspan extension. Despite these beneficial effects, epidemiological studies have shown that altered BCAA plasma concentrations and BCAA metabolism are present in several metabolic disorders, including type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD)...
September 17, 2016: British Journal of Pharmacology
Lorna Mulvey, William A Sands, Karine Salin, Amanda E Carr, Colin Selman
Dietary restriction (DR) extends lifespan and healthspan in many species, but precisely how it elicits its beneficial effects is unclear. We investigated the impact of DR on mitochondrial function within liver and skeletal muscle of female ILSXISS mice that exhibit strain-specific variation in lifespan under 40% DR. Strains TejJ89 (lifespan increased under DR), TejJ48 (lifespan unaffected by DR) and TejJ114 (lifespan decreased under DR) were studied following 10 months of 40% DR (13 months of age). Oxygen consumption rates (OCR) within isolated liver mitochondria were unaffected by DR in TejJ89 and TejJ48, but decreased by DR in TejJ114...
September 2, 2016: Molecular and Cellular Endocrinology
Scott F Leiser, Gholamali Jafari, Melissa Primitivo, George L Sutphin, Jingyi Dong, Alison Leonard, Marissa Fletcher, Matt Kaeberlein
Improving healthspan, defined as the period where organisms live without frailty and/or disease, is a major goal of biomedical research. While healthspan measures in people are relatively easy to identify, developing robust markers of healthspan in model organisms has proven challenging. Studies using the nematode Caenorhabditis elegans have provided vital information on the basic mechanisms of aging; however, worm health is difficult to define, and the impact of interventions that increase lifespan on worm healthspan has been controversial...
August 26, 2016: Age (2005-)
R C Coll, Laj O'Neill, K Schroder
The NLRP3 inflammasome is a key component of the innate immune system that induces pro-inflammatory cytokine production and cell death. Although NLRP3 is activated by many pathogens, it only appears to be critical for host defense for a limited number of specific infections. NLRP3 is however strongly associated with the initiation and pathology of many inflammatory diseases. If NLRP3 function is largely redundant for host defense, but drives a number of inflammatory diseases, this raises the important question of why evolution has elected to maintain NLRP3 function...
2016: Cell Death Discovery
Alessandro Bitto, Takashi K Ito, Victor V Pineda, Nicolas J LeTexier, Heather Z Huang, Elissa Sutlief, Herman Tung, Nicholas Vizzini, Belle Chen, Kaleb Smith, Daniel Meza, Masanao Yajima, Richard P Beyer, Kathleen F Kerr, Daniel J Davis, Catherine H Gillespie, Jessica M Snyder, Piper M Treuting, Matt Kaeberlein
The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine...
2016: ELife
Michael Sagner, Amy McNeil, Pekka Puska, Charles Auffray, Nathan D Price, Leroy Hood, Carl J Lavie, Ze-Guang Han, Zhu Chen, Samir Kumar Brahmachari, Bruce S McEwen, Marcelo B Soares, Rudi Balling, Elissa Epel, Ross Arena
Chronic diseases (i.e., noncommunicable diseases), mainly cardiovascular disease, cancer, respiratory diseases and type-2-diabetes, are now the leading cause of death, disability and diminished quality of life on the planet. Moreover, these diseases are also a major financial burden worldwide, significantly impacting the economy of many countries. Healthcare systems and medicine have progressively improved upon the ability to address infectious diseases and react to adverse health events through both surgical interventions and pharmacology; we have become efficient in delivering reactive care (i...
August 18, 2016: Progress in Cardiovascular Diseases
Jasper Most, Valeria Tosti, Leanne M Redman, Luigi Fontana
Calorie restriction (CR), a nutritional intervention of reduced energy intake but with adequate nutrition, has been shown to extend healthspan and lifespan in rodent and primate models. Accumulating data from observational and randomized clinical trials indicate that CR in humans results in some of the same metabolic and molecular adaptations that have been shown to improve health and retard the accumulation of molecular damage in animal models of longevity. In particular, moderate CR in humans ameliorates multiple metabolic and hormonal factors that are implicated in the pathogenesis of type 2 diabetes, cardiovascular diseases, and cancer, the leading causes of morbidity, disability and mortality...
August 17, 2016: Ageing Research Reviews
James L Kirkland, Michael B Stout, Felipe Sierra
Recently discovered interventions that target fundamental aging mechanisms have been shown to increase life span in mice and other species, and in some cases, these same manipulations have been shown to enhance healthspan and alleviate multiple age-related diseases and conditions. Aging is generally associated with decreases in resilience, the capacity to respond to or recover from clinically relevant stresses such as surgery, infections, or vascular events. We hypothesize that the age-related increase in susceptibility to those diseases and conditions is driven by or associated with the decrease in resilience...
August 16, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Sara Gelino, Jessica T Chang, Caroline Kumsta, Xingyu She, Andrew Davis, Christian Nguyen, Siler Panowski, Malene Hansen
[This corrects the article DOI: 10.1371/journal.pgen.1006135.].
August 2016: PLoS Genetics
Seong Kyu Han, Dongyeop Lee, Heetak Lee, Donghyo Kim, Heehwa G Son, Jae-Seong Yang, Seung-Jae V Lee, Sanguk Kim
Online application for survival analysis (OASIS) has served as a popular and convenient platform for the statistical analysis of various survival data, particularly in the field of aging research. With the recent advances in the fields of aging research that deal with complex survival data, we noticed a need for updates to the current version of OASIS. Here, we report OASIS 2 (, which provides extended statistical tools for survival data and an enhanced user interface. In particular, OASIS 2 enables the statistical comparison of maximal lifespans, which is potentially useful for determining key factors that limit the lifespan of a population...
August 12, 2016: Oncotarget
Alexander M Vaiserman, Oleh V Lushchak, Alexander K Koliada
Life expectancy has grown dramatically in modern times. This increase, however, is not accompanied by the same increase in healthspan. Efforts to extend healthspan through pharmacological agents targeting aging-related pathological changes are now in the spotlight of geroscience, the main idea of which is that delaying of aging is far more effective than preventing the particular chronic disorders. Currently, anti-aging pharmacology is a rapidly developing discipline. It is a preventive field of health care, as opposed to conventional medicine which focuses on treating symptoms rather than root causes of illness...
November 2016: Ageing Research Reviews
Asael Roichman, Yariv Kanfi, Renana Glazz, Shoshana Naiman, Uri Amit, Natalie Landa, Simon Tinman, Ilan Stein, Eli Pikarsky, Jonathan Leor, Haim Y Cohen
The extension in human lifespan in the last century results in a significant increase in incidence of age related diseases. It is therefore crucial to identify key factors that control elderly healthspan. Similar to dietary restriction, mice overexpressing the NAD(+) dependent protein deacylase SIRT6 (MOSES) live longer and have reduced IGF-1 levels. However, it is as yet unknown whether SIRT6 also affects various healthspan parameters. Here, a range of age related phenotypes was evaluated in MOSES mice. In comparison to their wild-type (WT) littermates, old MOSES mice showed amelioration of a variety of age-related disorders, including: improved glucose tolerance, younger hormonal profile, reduced age-related adipose inflammation and increased physical activity...
August 12, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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