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https://www.readbyqxmd.com/read/28802803/metformin-reduces-all-cause-mortality-and-diseases-of-ageing-independent-of-its-effect-on-diabetes-control-a-systematic-review-and-meta-analysis
#1
REVIEW
Jared M Campbell, Susan M Bellman, Matthew D Stephenson, Karolina Lisy
This systematic review investigated whether the insulin sensitiser metformin has a geroprotective effect in humans. Pubmed and Embase were searched along with databases of unpublished studies. Eligible research investigated the effect of metformin on all-cause mortality or diseases of ageing relative to non-diabetic populations or diabetics receiving other therapies with adjustment for disease control achieved. Overall, 260 full-texts were reviewed and 53 met the inclusion criteria. Diabetics taking metformin had significantly lower all-cause mortality than non-diabetics (hazard ratio (HR)=0...
August 9, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28797825/mechanisms-underlying-longevity-a-genetic-switch-model-of-aging
#2
REVIEW
Jeremy M Van Raamsdonk
While the questions of "What causes aging?" and "Why do we age?" and "How can we stop it?" remain unanswered, recent advances in aging research have continued to increase our understanding of the aging process. Until the last couple of decades, aging was viewed as an inevitable process of damage accumulation and not a subject for scientific pursuit. This view changed when it was demonstrated that the aging process is in fact malleable and genetically determined: mutations in single genes can have dramatic effects on longevity...
August 7, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28795262/growth-factor-energy-and-nutrient-sensing-signalling-pathways-in-metabolic-ageing
#3
Lucia Bettedi, Lazaros C Foukas
The field of the biology of ageing has received increasing attention from a biomedical point of view over the past decades. The main reason has been the realisation that increases in human population life expectancy are accompanied by late onset diseases. Indeed, ageing is the most important risk factor for a number of neoplastic, neurodegenerative and metabolic pathologies. Advances in the knowledge of the genetics of ageing, mainly through research in model organisms, have implicated various cellular processes and the respective signalling pathways that regulate them in cellular and organismal ageing...
August 9, 2017: Biogerontology
https://www.readbyqxmd.com/read/28768895/p16-ink4a-and-senescence-associated-%C3%AE-galactosidase-can-be-induced-in-macrophages-as-part-of-a-reversible-response-to-physiological-stimuli
#4
Brandon M Hall, Vitaly Balan, Anatoli S Gleiberman, Evguenia Strom, Peter Krasnov, Lauren P Virtuoso, Elena Rydkina, Slavoljub Vujcic, Karina Balan, Ilya I Gitlin, Katerina I Leonova, Camila R Consiglio, Sandra O Gollnick, Olga B Chernova, Andrei V Gudkov
Constitutive p16(Ink4a) expression, along with senescence-associated β-galactosidase (SAβG), are commonly accepted biomarkers of senescent cells (SCs). Recent reports attributed improvement of the healthspan of aged mice following p16(Ink4a)-positive cell killing to the eradication of accumulated SCs. However, detection of p16(Ink4a)/SAβG-positive macrophages in the adipose tissue of old mice and in the peritoneal cavity of young animals following injection of alginate-encapsulated SCs has raised concerns about the exclusivity of these markers for SCs...
August 2, 2017: Aging
https://www.readbyqxmd.com/read/28751929/the-preconditioning-of-berberine-suppresses-hydrogen-peroxide-induced-premature-senescence-via-regulation-of-sirtuin-1
#5
Xiaofei Zhu, Haodi Yue, Xiaofang Guo, Jingyi Yang, Jingshuo Liu, Jiangtao Liu, Ruijie Wang, Wenjuan Zhu
With a long history of application in Chinese traditional medicine, berberine (BBR) was reported to exhibit healthspan-extending properties in some age-related diseases, such as type 2 diabetes and atherosclerosis. However, the antiaging mechanism of BBR is not completely clear. By means of hydrogen peroxide- (H2O2-) induced premature cellular senescence model, we found that a low-concentration preconditioning of BBR could resist premature senescence in human diploid fibroblasts (HDFs) measured by senescence-associated β-galactosidase (SA-β-gal), accompanied by a decrease in loss of mitochondrial membrane potential and production of intracellular reactive oxygen species (ROS)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28740165/myricetin-improves-endurance-capacity-and-mitochondrial-density-by-activating-sirt1-and-pgc-1%C3%AE
#6
Hoe-Yune Jung, Dongyeop Lee, Hye Guk Ryu, Bo-Hwa Choi, Younghoon Go, Namgyu Lee, Dohyun Lee, Heehwa G Son, Jongsu Jeon, Seong-Hoon Kim, Jong Hyuk Yoon, Seon-Min Park, Seung-Jae V Lee, In-Kyu Lee, Kwan Yong Choi, Sung Ho Ryu, Kazunari Nohara, Seung-Hee Yoo, Zheng Chen, Kyong-Tai Kim
Robust mitochondrial respiration provides energy to support physical performance and physiological well-being, whereas mitochondrial malfunction is associated with various pathologies and reduced longevity. In the current study, we tested whether myricetin, a natural flavonol with diverse biological activities, may impact mitochondrial function and longevity. The mice were orally administered myricetin (50 mg/kg/day) for 3 weeks. Myricetin significantly potentiated aerobic capacity in mice, as evidenced by their increased running time and distance...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728596/implementation-of-longevity-promoting-supplements-and-medications-in-public-health-practice-achievements-challenges-and-future-perspectives
#7
REVIEW
Alexander Vaiserman, Oleh Lushchak
BACKGROUND: Most modern societies undergo rapid population aging. The rise in life expectancy, nevertheless, is not accompanied, to date, by the same increment of healthspan. Efforts to increase healthspan by means of supplements and pharmaceuticals targeting aging-related pathologies are presently in spotlight of a new branch in geriatric medicine, geroscience, postulating that aging could be manipulated in such a way that will in parallel allow delay the onset of all age-associated chronic disorders...
July 20, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28718225/proteostasis-and-ageing-insights-from-long-lived-mutant-mice
#8
William A Sands, Melissa M Page, Colin Selman
The global increase in life expectancy is creating significant medical, social and economic challenges to current and future generations. Consequently, there is a need to identify the fundamental mechanisms underlying the ageing process. This knowledge should help develop realistic interventions capable of combatting age-related disease, and thus improving late-life health and vitality. While several mechanisms have been proposed as conserved lifespan determinants, the loss of proteostasis- where proteostasis is defined here as the maintenance of the proteome- appears highly relevant to both ageing and disease...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28714416/application-of-kinase-inhibitors-for-anti-aging-intervention
#9
Mercedes Cano, Antonio Ayala, Francesco Marotta, Sandro Argüelles
Protein phosphorylation, mediated by protein kinases, has important physiological and pathological implications in our lives . Targeting kinase is one of the most interesting of the emerging topics in the pharmaceutical industry, especially since there is a focus on cancer therapy. Given that kinases may be involved in the aging process the focus will be on using the kinase inhibitor for anti-aging intervention to enhance healthspan and increase longevity. In this review , we will summarize: (i) the impact of the phosphoproteomic approach to elucidate molecular mechanisms of diseases; (ii) importance of the drug discovery approach for targeting kinases; (iii) the dysregulation of Janus kinase (JAK) / signal-transducing adapter molecules (STAT) and p70 ribosomal protein S6 kinase (S6Ks) pathway in aging and the age-related process; (iv) the epidemiological studies available in order to see whether a correlation between JAK/STAT and S6Ks mRNA expression levels exist in cancer and in patient outcome; (v) finally, we will show selected inhibitors of these kinases approved by the US Food and Drug Administration (FDA)...
July 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28698312/approaches-for-extending-human-healthspan-from-antioxidants-to-healthspan-pharmacology
#10
REVIEW
Jan Gruber, Barry Halliwell
Dramatic increases in human lifespan and declining population growth are monumental achievements but these same achievements have also led to many societies today ageing at a faster rate than ever before. Extending healthy lifespan (healthspan) is a key translational challenge in this context. Disease-centric approaches to manage population ageing risk are adding years to life without adding health to these years. The growing consensus that ageing is driven by a limited number of interconnected processes suggests an alternative approach...
July 15, 2017: Essays in Biochemistry
https://www.readbyqxmd.com/read/28667441/lifespan-extending-and-stress-resistance-properties-of-brazilin-from-caesalpinia-sappan-in-caenorhabditis-elegans
#11
Eun Byeol Lee, Ming Ming Xing, Dae Keun Kim
This study contributes to the continual discovery of lifespan-extending compounds from plants, using the Caenorhabditis elegans model system. An ethyl acetate soluble fraction of methanol extract from the heartwood of Caesalpinia sappan showed a significant lifespan-extending activity. Subsequent activity-guided chromatography of the ethyl acetate-soluble fraction led to the isolation of brazilin. Brazilin showed potent 2,2-diphenyl-1-picrylhydrazyl radical scavenging and superoxide anion quenching activities and also revealed a lifespan-extending activity in C...
June 30, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28658611/interventions-to-slow-cardiovascular-aging-dietary-restriction-drugs-and-novel-molecules
#12
REVIEW
Christian Heiss, Ioakim Spyridopoulos, Judith Haendeler
Cardiovascular aging is a highly dynamic process. Despite the fact that cardiovascular function and structure change with age, they can still be modulated even in aged humans. The most prominent approaches to improve age-dependent vascular changes include dietary restriction and pharmacologic agents interacting with signaling pathways implicated in this context. These include inhibition of TOR, glycolysis, and GH/IGF-1, activation of sirtuins, and AMPK, as well as modulators of inflammation, epigenetic pathways, and telomeres...
June 27, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28649426/conserved-and-species-specific-molecular-denominators-in-mammalian-skeletal-muscle-aging
#13
Evi M Mercken, Miriam Capri, Bethany A Carboneau, Maria Conte, Juliana Heidler, Aurelia Santoro, Alejandro Martin-Montalvo, Marta Gonzalez-Freire, Husam Khraiwesh, José A González-Reyes, Ruin Moaddel, Yongqing Zhang, Kevin G Becker, José M Villalba, Julie A Mattison, Ilka Wittig, Claudio Franceschi, Rafael de Cabo
Aging is a complex phenomenon involving functional decline in multiple physiological systems. We undertook a comparative analysis of skeletal muscle from four different species, i.e. mice, rats, rhesus monkeys, and humans, at three different representative stages during their lifespan (young, middle, and old) to identify pathways that modulate function and healthspan. Gene expression profiling and computational analysis revealed that pathway complexity increases from mice to humans, and as mammals age, there is predominantly an upregulation of pathways in all species...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28610949/calorie-restriction-in-rodents-caveats-to-consider
#14
REVIEW
Donald K Ingram, Rafael de Cabo
The calorie restriction paradigm has provided one of the most widely used and most useful tools for investigating mechanisms of aging and longevity. By far, rodent models have been employed most often in these endeavors. Over decades of investigation, claims have been made that the paradigm produces the most robust demonstration that aging is malleable. In the current review of the rodent literature, we present arguments that question the robustness of the paradigm to increase lifespan and healthspan. Specifically, there are several questions to consider as follows: (1) At what age does CR no longer produce benefits? (2) Does CR attenuate cognitive decline? (3) Are there negative effects of CR, including effects on bone health, wound healing, and response to infection? (4) How important is schedule of feeding? (5) How long does CR need to be imposed to be effective? (6) How do genotype and gender influence CR? (7) What role does dietary composition play? Consideration of these questions produce many caveats that should guide future investigations to move the field forward...
June 10, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28585366/advances-in-therapeutic-approaches-to-extend-healthspan-a-perspective-from-the-2-nd-scripps-symposium-on-the-biology-of-aging
#15
Paul D Robbins, Laura J Niedernhofer
The 2(nd) Scripps Florida Symposium on The Biology of Aging entitled 'Advances in Therapeutic Approaches to Extend Healthspan' was held on January 22(nd) -25(th) , 2017 at The Scripps Research Institute in Jupiter, Florida. The meeting highlighted a variety of therapeutic approaches in animal models of aging that either are or soon will be in clinic trials. For example, drugs targeting senescent cells, metformin, rapalogs, NAD precursors, young plasma, mitochondrial-targeted free radical scavengers, stem cells, and stem cell factors all have shown significant preclinical efficacy...
August 2017: Aging Cell
https://www.readbyqxmd.com/read/28575157/sex-differences-in-aging-genomic-instability
#16
Kathleen E Fischer, Nicole C Riddle
Aging is characterized by decreasing physiological integration, reduced function, loss of resilience and increased risk of death. Paradoxically, although women live longer, they suffer greater morbidity particularly late in life. These sex differences in human lifespan and healthspan are consistently observed in all countries and during every era for which reliable data exist. While these differences are ubiquitous in humans, evidence of sex differences in longevity and health for other species is more equivocal...
June 2, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28559281/uridine-monophosphate-synthetase-enables-eukaryotic-de-novo-nad-biosynthesis-from-quinolinic-acid
#17
Melanie R McReynolds, Wenqing Wang, Lauren M Holleran, Wendy Hanna-Rose
NAD(+) biosynthesis is an attractive and promising therapeutic target for influencing health span and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD(+) biosynthetic pathways. Here, we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD(+) biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD(+) biosynthetic pathway...
July 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28556428/identification-of-tissue-specific-transcriptional-markers-of-caloric-restriction-in-the-mouse-and-their-use-to-evaluate-caloric-restriction-mimetics
#18
Jamie L Barger, James M Vann, Nicole L Cray, Thomas D Pugh, Angela Mastaloudis, Shelly N Hester, Steven M Wood, Michael A Newton, Richard Weindruch, Tomas A Prolla
Caloric restriction (CR) without malnutrition has been shown to retard several aspects of the aging process and to extend lifespan in different species. There is strong interest in the identification of CR mimetics (CRMs), compounds that mimic the beneficial effects of CR on lifespan and healthspan without restriction of energy intake. Identification of CRMs in mammals is currently inefficient due to the lack of screening tools. We have performed whole-genome transcriptional profiling of CR in seven mouse strains (C3H/HeJ, CBA/J, DBA/2J, B6C3F1/J, 129S1/SvImJ, C57BL/6J, and BALB/cJ) in white adipose tissue (WAT), gastrocnemius muscle, heart, and brain neocortex...
August 2017: Aging Cell
https://www.readbyqxmd.com/read/28552719/regulation-of-longevity-by-fgf21-interaction-between-energy-metabolism-and-stress-responses
#19
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
Fibroblast growth factor 21 (FGF21) is a hormone-like member of FGF family which controls metabolic multiorgan crosstalk enhancing energy expenditure through glucose and lipid metabolism. In addition, FGF21 acts as a stress hormone induced by endoplasmic reticulum stress and dysfunctions of mitochondria and autophagy in several tissues. FGF21 also controls stress responses and metabolism by modulating the functions of somatotropic axis and hypothalamic-pituitary-adrenal (HPA) pathway. FGF21 is a potent longevity factor coordinating interactions between energy metabolism and stress responses...
August 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28551577/bioactive-growth-hormone-in-older-men-and-women-it-s-relationship-to-immune-markers-and-healthspan
#20
William J Kraemer, Mary J Kennett, Andrea M Mastro, Roger J McCarter, Connie J Rogers, William H DuPont, Shawn D Flanagan, William J Turbitt, Maren S Fragala, Emily M Post, Wesley C Hymer
OBJECTIVE: The consequences of age-related decline in the somatotropic axis of humans are complex and remain largely unresolved. We tested the hypothesis that hGH measurements of plasma by bioassay vs immunoassay from samples obtained from free-living, elderly individuals would reveal a dichotomy in GH activities that are correlated with the functional status of the donors, i.e. their healthspan. DESIGN: Forty-one men and women of advanced age (men: N=16, age, 80...
June 2017: Growth Hormone & IGF Research
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