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https://www.readbyqxmd.com/read/28340339/targeted-apoptosis-of-senescent-cells-restores-tissue-homeostasis-in-response-to-chemotoxicity-and-aging
#1
Marjolein P Baar, Renata M C Brandt, Diana A Putavet, Julian D D Klein, Kasper W J Derks, Benjamin R M Bourgeois, Sarah Stryeck, Yvonne Rijksen, Hester van Willigenburg, Danny A Feijtel, Ingrid van der Pluijm, Jeroen Essers, Wiggert A van Cappellen, Wilfred F van IJcken, Adriaan B Houtsmuller, Joris Pothof, Ron W F de Bruin, Tobias Madl, Jan H J Hoeijmakers, Judith Campisi, Peter L J de Keizer
The accumulation of irreparable cellular damage restricts healthspan after acute stress or natural aging. Senescent cells are thought to impair tissue function, and their genetic clearance can delay features of aging. Identifying how senescent cells avoid apoptosis allows for the prospective design of anti-senescence compounds to address whether homeostasis can also be restored. Here, we identify FOXO4 as a pivot in senescent cell viability. We designed a FOXO4 peptide that perturbs the FOXO4 interaction with p53...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28325885/physiological-frailty-index-pfi-quantitative-in-life-estimate-of-individual-biological-age-in-mice
#2
Marina P Antoch, Michelle Wrobel, Karen K Kuropatwinski, Ilya Gitlin, Katerina I Leonova, Ilia Toshkov, Anatoli S Gleiberman, Alan D Hutson, Olga B Chernova, Andrei V Gudkov
The development of healthspan-extending pharmaceuticals requires quantitative estimation of age-related progressive physiological decline. In humans, individual health status can be quantitatively assessed by means of a frailty index (FI), a parameter which reflects the scale of accumulation of age-related deficits. However, adaptation of this methodology to animal models is a challenging task since it includes multiple subjective parameters. Here we report a development of a quantitative non-invasive procedure to estimate biological age of an individual animal by creating physiological frailty index (PFI)...
March 19, 2017: Aging
https://www.readbyqxmd.com/read/28314502/nutrient-sensing-and-the-oxidative-stress-response
#3
REVIEW
Hanzhi Luo, Hou-Hsien Chiang, Makensie Louw, Albert Susanto, Danica Chen
The simplicity and effectiveness of calorie restriction (CR) in lifespan and healthspan extension have fascinated generations searching for the Fountain of Youth. CR reduces levels of oxidative stress and damage, which have been postulated in the free radical theory of aging as a major cause of aging and diseases of aging. This reduction has long been viewed as a result of passive slowing of metabolism. Recent advances in nutrient sensing have provided molecular insights into the oxidative stress response and suggest that CR triggers an active defense program involving a cascade of molecular regulators to reduce oxidative stress...
March 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28299635/geroscience-and-the-trans-nih-geroscience-interest-group-gsig
#4
EDITORIAL
Felipe Sierra, Ron Kohanski
Age is by far the major risk factor for most chronic diseases. This has been common knowledge since time immemorial. Aging encompasses the biological changes most often seen as declines of function and increasing burden of disease. The close linkage of these two has led people to believe that aging, like age, is immutable. It is only recently that research into the basic molecular and cellular mechanisms of aging has led to potential interventions that increase lifespan and appear to increase healthspan, as well...
February 2017: Geroscience
https://www.readbyqxmd.com/read/28280523/resveratrol-attenuates-copper-induced-senescence-by-improving-cellular-proteostasis
#5
Liliana Matos, Alexandra Monteiro Gouveia, Henrique Almeida
Copper sulfate-induced premature senescence (CuSO4-SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28258519/sirtuins-a-promising-target-in-slowing-down-the-ageing-process
#6
REVIEW
Wioleta Grabowska, Ewa Sikora, Anna Bielak-Zmijewska
Ageing is a plastic process and can be successfully modulated by some biomedical approaches or pharmaceutics. In this manner it is possible to delay or even prevent some age-related pathologies. There are some defined interventions, which give promising results in animal models or even in human studies, resulting in lifespan elongation or healthspan improvement. One of the most promising targets for anti-ageing approaches are proteins belonging to the sirtuin family. Sirtuins were originally discovered as transcription repressors in yeast, however, nowadays they are known to occur in bacteria and eukaryotes (including mammals)...
March 3, 2017: Biogerontology
https://www.readbyqxmd.com/read/28253986/mitochondrial-targeted-catalase-extended-longevity-and-the-roles-in-various-disease-models
#7
D-F Dai, Y-A Chiao, G M Martin, D J Marcinek, N Basisty, E K Quarles, P S Rabinovitch
The free-radical theory of aging was proposed more than 50 years ago. As one of the most popular mechanisms explaining the aging process, it has been extensively studied in several model organisms. However, the results remain controversial. The mitochondrial version of free-radical theory of aging proposes that mitochondria are both the primary sources of reactive oxygen species (ROS) and the primary targets of ROS-induced damage. One critical ROS is hydrogen peroxide, which is naturally degraded by catalase in peroxisomes or glutathione peroxidase within mitochondria...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28251407/jujube-ziziphus-jujuba-mill-fruit-feeding-extends-lifespan-and-increases-tolerance-to-environmental-stresses-by-regulating-aging-associated-gene-expression-in-drosophila
#8
Saurav Ghimire, Man Su Kim
Jujube (Ziziphus Jujuba Mill.) fruit has been utilized as an adjunct to alleviate medical symptoms including, but not limited to, anorexia, fatigue, anxiety and mild diarrhea for centuries. Despite a growing body of literature revealing jujube fruit's health promoting properties such as anti-cancer, anti-inflammation and anti-oxidant effects (shown with cell-based in vitro platforms), there is a paucity of studies systemically examining its impact on whole organisms or throughout the entire course of life utilizing in vivo model systems...
March 1, 2017: Biogerontology
https://www.readbyqxmd.com/read/28208582/nutrients-in-energy-and-one-carbon-metabolism-learning-from-metformin-users
#9
REVIEW
Fedra Luciano-Mateo, Anna Hernández-Aguilera, Noemi Cabre, Jordi Camps, Salvador Fernández-Arroyo, Jose Lopez-Miranda, Javier A Menendez, Jorge Joven
Metabolic vulnerability is associated with age-related diseases and concomitant co-morbidities, which include obesity, diabetes, atherosclerosis and cancer. Most of the health problems we face today come from excessive intake of nutrients and drugs mimicking dietary effects and dietary restriction are the most successful manipulations targeting age-related pathways. Phenotypic heterogeneity and individual response to metabolic stressors are closely related food intake. Understanding the complexity of the relationship between dietary provision and metabolic consequences in the long term might provide clinical strategies to improve healthspan...
February 10, 2017: Nutrients
https://www.readbyqxmd.com/read/28203479/metformin-impairs-spatial-memory-and-visual-acuity-in-old-male-mice
#10
Nopporn Thangthaeng, Margaret Rutledge, Jessica M Wong, Philip H Vann, Michael J Forster, Nathalie Sumien
Metformin is an oral anti-diabetic used as first-line therapy for type 2 diabetes. Because benefits of metformin extend beyond diabetes to other age-related pathology, and because its effect on gene expression profiles resembles that of caloric restriction, metformin has a potential as an anti-aging intervention and may soon be assessed as an intervention to extend healthspan. However, beneficial actions of metformin in the central nervous system have not been clearly established. The current study examined the effect of chronic oral metformin treatment on motor and cognitive function when initiated in young, middle-aged, or old male mice...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28202600/neoteny-prolongation-of-youth-from-naked-mole-rats-to-naked-apes-humans
#11
REVIEW
Vladimir P Skulachev, Susanne Holtze, Mikhail Y Vyssokikh, Lora E Bakeeva, Maxim V Skulachev, Alexander V Markov, Thomas B Hildebrandt, Viktor A Sadovnichii
It has been suggested that highly social mammals, such as naked mole rats and humans, are long-lived due to neoteny (the prolongation of youth). In both species, aging cannot operate as a mechanism facilitating natural selection because the pressure of this selection is strongly reduced due to 1) a specific social structure where only the "queen" and her "husband(s)" are involved in reproduction (naked mole rats) or 2) substituting fast technological progress for slow biological evolution (humans). Lists of numerous traits of youth that do not disappear with age in naked mole rats and humans are presented and discussed...
April 2017: Physiological Reviews
https://www.readbyqxmd.com/read/28198412/a-screening-strategy-for-the-discovery-of-drugs-that-reduce-c-ebp%C3%AE-lip-translation-with-potential-calorie-restriction-mimetic-properties
#12
Mohamad A Zaini, Christine Müller, Tobias Ackermann, Jeanette Reinshagen, Gertrud Kortman, Ole Pless, Cornelis F Calkhoven
An important part of the beneficial effects of calorie restriction (CR) on healthspan and lifespan is mediated through regulation of protein synthesis that is under control of the mechanistic target of rapamycin complex 1 (mTORC1). As one of its activities, mTORC1 stimulates translation into the metabolic transcription factor CCAAT/Enhancer Binding Protein β (C/EBPβ) isoform Liver-specific Inhibitory Protein (LIP). Regulation of LIP expression strictly depends on a translation re-initiation event that requires a conserved cis-regulatory upstream open reading frame (uORF) in the C/EBPβ-mRNA...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28158260/effects-of-calorie-restriction-on-the-lifespan-and-healthspan-of-polg-mitochondrial-mutator-mice
#13
Shinichi Someya, Gregory C Kujoth, Mi-Jung Kim, Timothy A Hacker, Marc Vermulst, Richard Weindruch, Tomas A Prolla
Mitochondrial DNA (mtDNA) mutations are thought to have a causative role in age-related pathologies. We have shown previously that mitochondrial mutator mice (PolgD257A/D257A), harboring a proofreading-deficient version of the mtDNA polymerase gamma (POLG), accumulate mtDNA mutations in multiple tissues and display several features of accelerated aging. Calorie restriction (CR) is known to delay the onset of age-related diseases and to extend the lifespan of a variety of species, including rodents. In the current study we investigated the effects of CR on the lifespan and healthspan of mitochondrial mutator mice...
2017: PloS One
https://www.readbyqxmd.com/read/28126607/healthy-living-the-universal-and-timeless-medicine-for-healthspan
#14
EDITORIAL
Ross Arena, Amy McNeil, Michael Sagner, Carl J Lavie
No abstract text is available yet for this article.
January 23, 2017: Progress in Cardiovascular Diseases
https://www.readbyqxmd.com/read/28108330/pleiotropic-responses-to-methionine-restriction
#15
Gene P Ables, Jay E 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
#16
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
#17
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...
April 2017: Aging Cell
https://www.readbyqxmd.com/read/28035340/targeting-glucose-metabolism-for-healthy-aging
#18
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
#19
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
#20
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
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