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https://www.readbyqxmd.com/read/29340835/repurposed-fda-approved-drugs-targeting-genes-influencing-aging-can-extend-lifespan-and-healthspan-in-rotifers
#1
Terry W Snell, Rachel K Johnston, Amelia B Matthews, Hongyi Zhou, Mu Gao, Jeffrey Skolnick
Pharmaceutical interventions can slow aging in animals, and have advantages because their dose can be tightly regulated and the timing of the intervention can be closely controlled. They also may complement environmental interventions like caloric restriction by acting additively. A fertile source for therapies slowing aging is FDA approved drugs whose safety has been investigated. Because drugs bind to several protein targets, they cause multiple effects, many of which have not been characterized. It is possible that some of the side effects of drugs prescribed for one therapy may have benefits in retarding aging...
January 16, 2018: Biogerontology
https://www.readbyqxmd.com/read/29340834/limited-daily-feeding-and-intermittent-feeding-have-different-effects-on-regional-brain-energy-homeostasis-during-aging
#2
Kosara Smiljanic, Smilja Todorovic, Aleksandra Mladenovic Djordjevic, Tim Vanmierlo, Dieter Lütjohann, Sanja Ivkovic, Selma Kanazir
Albeit aging is an inevitable process, the rate of aging is susceptible to modifications. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay aging and increase healthspan in diverse species. This study aimed to compare the impact of different restricting feeding regimes such as limited daily feeding (LDF, 60% AL) and intermittent feeding (IF) on brain energy homeostasis during aging. The analysis was focused on the key molecules in glucose and cholesterol metabolism in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats...
January 16, 2018: Biogerontology
https://www.readbyqxmd.com/read/29301845/elixir-of-life-thwarting-aging-with-regenerative-reprogramming
#3
REVIEW
Ergin Beyret, Paloma Martinez Redondo, Aida Platero Luengo, Juan Carlos Izpisua Belmonte
All living beings undergo systemic physiological decline after ontogeny, characterized as aging. Modern medicine has increased the life expectancy, yet this has created an aged society that has more predisposition to degenerative disorders. Therefore, novel interventions that aim to extend the healthspan in parallel to the life span are needed. Regeneration ability of living beings maintains their biological integrity and thus is the major leverage against aging. However, mammalian regeneration capacity is low and further declines during aging...
January 5, 2018: Circulation Research
https://www.readbyqxmd.com/read/29277395/circadian-regulation-of-metabolism-and-healthspan-in-drosophila
#4
REVIEW
Jadwiga M Giebultowicz
Circadian clocks generate daily rhythms in gene expression, cellular functions, physiological processes and behavior. The core clock mechanism consists of transcriptional-translational negative feedback loops that turn over with an endogenous circa 24h period. Classical genetic experiments in the fly Drosophila melanogaster played an essential role in identification of clock genes that turned out to be largely conserved between flies and mammals. Like in mammals, circadian clocks in flies generate transcriptional rhythms in a variety of metabolic pathways related to feeding and detoxification...
December 19, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29276113/ayurveda-and-the-science-of-aging
#5
REVIEW
Rammohan V Rao
Since time immemorial, humanity has been concerned with developing and preserving youthful vigor, and extending longevity by stopping or delaying the aging process. By 2030, one in five of the world population will be over 65 years old. Longevity and old age are accompanied with a variety of health challenges and population studies indicate that the elderly will use between three to five times more healthcare services compared to the younger population. Modern medicine has made a great deal of progress in understanding the aging process and in controlling age-associated health issues including heart attacks, strokes, diabetes, cancer, senility, and arthritis...
December 21, 2017: Journal of Ayurveda and Integrative Medicine
https://www.readbyqxmd.com/read/29275161/aging-inflammation-and-the-environment
#6
REVIEW
Arsun Bektas, Shepherd H Schurman, Ranjan Sen, Luigi Ferrucci
The aging process is driven by interrelated mechanisms that lead to the emergence of characteristic phenotypes that include changes in body composition, energy production and utilization imbalance, homeostatic dysregulation, and neurodegeneration and loss of neuroplasticity. Mainstream theories of aging all recognize that the aging phenotypes result from an imbalance between stressors and stress buffering mechanisms and a resultant loss of compensatory reserve leading to accumulation of unrepaired damage. This in turn results in increased disease susceptibility, reduced functional reserve, reduced healing capacity and stress resistance, unstable health and finally failure to thrive...
December 21, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29259189/milder-degenerative-effects-of-carfilzomib-vs-bortezomib-in-the-drosophila-model-a-link-to-clinical-adverse-events
#7
Eleni N Tsakiri, Evangelos Terpos, Eleni-Dimitra Papanagnou, Efstathios Kastritis, Vincent Brieudes, Maria Halabalaki, Tina Bagratuni, Bogdan I Florea, Herman S Overkleeft, Luca Scorrano, Alexios-Leandros Skaltsounis, Meletios A Dimopoulos, Ioannis P Trougakos
Proteasome inhibitors, e.g. Bortezomib (BTZ) and Carfilzomib (CFZ), have demonstrated clinical efficacy against haematological cancers. Interestingly, several adverse effects are less common, compared to BTZ, in patients treated with CFZ. As the molecular details of these observations remain not well understood we assayed the pathophysiological effects of CFZ vs. BTZ in the Drosophila experimental model. Mass Spectrometry analyses showed that neither CFZ nor BTZ are hydrolysed in flies' tissues, while at doses inducing similar inhibition of the rate limiting for protein breakdown chymotrypsin-like (CT-L) proteasomal activity, CFZ treatment resulted in less intense increase of oxidative stress or activation of antioxidant and proteostatic modules...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29214707/movement-decline-across-lifespan-of-caenorhabditis-elegans-mutants-in-the-insulin-insulin-like-signaling-pathway
#8
Breanne L Newell Stamper, James R Cypser, Katerina Kechris, David Alan Kitzenberg, Patricia M Tedesco, Thomas E Johnson
Research in aging biology has identified several pathways that are molecularly conserved across species that extend lifespan when mutated. The insulin/insulin-like signaling (IIS) pathway is one of the most widely studied of these. It has been assumed that extending lifespan also extends healthspan (the period of life with minimal functional loss). However, data supporting this assumption conflict and recent evidence suggest that life extension may, in and of itself, extend the frail period. In this study, we use Caenorhabditis elegans to further probe the link between lifespan and healthspan...
December 7, 2017: Aging Cell
https://www.readbyqxmd.com/read/29184395/does-eating-less-make-you-live-longer-and-better-an-update-on-calorie-restriction
#9
REVIEW
Anna Picca, Vito Pesce, Angela Maria Serena Lezza
The complexity of aging is hard to be captured. However, apart from its tissue-specific features, a structural and functional progressive decline of the whole organism that leads to death, often preceded by a phase of chronic morbidity, characterizes the common process of aging. Therefore, the research goal of scientists in the field moved from the search for strategies able to extend longevity to those ensuring healthy aging associated with a longer lifespan referred to as "healthspan". The aging process is plastic and can be tuned by multiple mechanisms including dietary and genetic interventions...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/29179649/mesenchymal-stem-cells-for-frailty
#10
James Larrick, Andrew R Mendelsohn
Frailty is a medical syndrome associated with advancing age characterized by reduced functional reserve, strength, endurance and susceptibility to infection associated with high morbidity, hospitalization and death. Non-specific interventions to improve the healthspan of affected patients include physical therapy, exercise, improved nutrition, etc. Among the hallmarks of aging, depletion of stem cells with resultant compromise of regeneration and repair of tissues informs a rational stem cell-based replacement strategy...
November 27, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/29167799/the-integrated-stress-response-in-budding-yeast-lifespan-extension
#11
REVIEW
Spike D L Postnikoff, Jay E Johnson, Jessica K Tyler
Aging is a complex, multi-factorial biological process shared by all living organisms. It is manifested by a gradual accumulation of molecular alterations that lead to the decline of normal physiological functions in a time-dependent fashion. The ultimate goal of aging research is to develop therapeutic means to extend human lifespan, while reducing susceptibility to many age-related diseases including cancer, as well as metabolic, cardiovascular and neurodegenerative disorders. However, this first requires elucidation of the causes of aging, which has been greatly facilitated by the use of model organisms...
October 24, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29165314/towards-natural-mimetics-of-metformin-and-rapamycin
#12
Alexander Aliper, Leslie Jellen, Franco Cortese, Artem Artemov, Darla Karpinsky-Semper, Alexey Moskalev, Andrew G Swick, Alex Zhavoronkov
Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals-safer, naturally-occurring compounds-that mimic the anti-aging effects of metformin and rapamycin without adverse effects...
November 15, 2017: Aging
https://www.readbyqxmd.com/read/29141215/octopamine-drives-endurance-exercise-adaptations-in-drosophila
#13
Alyson Sujkowski, Divya Ramesh, Axel Brockmann, Robert Wessells
Endurance exercise is an effective therapeutic intervention with substantial pro-healthspan effects. Male Drosophila respond to a ramped daily program of exercise by inducing conserved physiological responses similar to those seen in mice and humans. Female flies respond to an exercise stimulus but do not experience the adaptive training response seen in males. Here, we use female flies as a model to demonstrate that differences in exercise response are mediated by differences in neuronal activity. The activity of octopaminergic neurons is specifically required to induce the conserved cellular and physiological changes seen following endurance training...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29135455/transcriptome-wide-association-study-of-inflammatory-biologic-age
#14
Honghuang Lin, Kathryn L Lunetta, Qiang Zhao, Jian Rong, Emelia J Benjamin, Michael M Mendelson, Roby Joehanes, Daniel Levy, Martin G Larson, Joanne M Murabito
Chronic low grade inflammation is a fundamental mechanism of aging. We estimated biologic age using nine biomarkers from diverse inflammatory pathways and we hypothesized that genes associated with inflammatory biological age would provide insights into human aging. In Framingham Offspring Study participants at examination 8 (2005 to 2008), we used the Klemera-Doubal method to estimate inflammatory biologic age and we computed the difference (∆Age) between biologic age and chronologic age. Gene expression in whole blood was measured using the Affymetrix Human Exon 1...
November 11, 2017: Aging
https://www.readbyqxmd.com/read/29133780/o-glcnacylation-of-sirt1-enhances-its-deacetylase-activity-and-promotes-cytoprotection-under-stress
#15
Cuifang Han, Yuchao Gu, Hui Shan, Wenyi Mi, Jiahui Sun, Minghui Shi, Xinling Zhang, Xinzhi Lu, Feng Han, Qianhong Gong, Wengong Yu
SIRT1 is the most evolutionarily conserved mammalian sirtuin, and it plays a vital role in the regulation of metabolism, stress responses, genome stability, and ageing. As a stress sensor, SIRT1 deacetylase activity is significantly increased during stresses, but the molecular mechanisms are not yet fully clear. Here, we show that SIRT1 is dynamically modified with O-GlcNAc at Ser 549 in its carboxy-terminal region, which directly increases its deacetylase activity both in vitro and in vivo. The O-GlcNAcylation of SIRT1 is elevated during genotoxic, oxidative, and metabolic stress stimuli in cellular and mouse models, thereby increasing SIRT1 deacetylase activity and protecting cells from stress-induced apoptosis...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29125735/resveratrol-exerts-antioxidant-effects-by-activating-sirt2-to-deacetylate-prx1
#16
Yanchao Pan, Hua Zhang, Yueting Zheng, Juanzuo Zhou, Jing Yuan, Yang Yu, Jiangyun Wang
Resveratrol is a promising chemical agent that treats multiple aging-related diseases and improves healthspan. While reactive oxygen species (ROS) undoubtedly play ubiquitous roles in the aging process and resveratrol has been shown to be an effective antioxidant, the mechanism through which resveratrol acts against oxidative stress remains unknown. Here we show that resveratrol activates Sirt2 to deacetylate Prx1, leading to increased H2O2 reduction activity and decreased cellular H2O2 concentration. Knockdown of Sirt2 or Prx1 by RNA interference abrogates resveratrol's ability to reduce H2O2 level in HepG2 cells...
November 10, 2017: Biochemistry
https://www.readbyqxmd.com/read/29117555/mitochondrial-stress-restores-the-heat-shock-response-and-prevents-proteostasis-collapse-during-aging
#17
Johnathan Labbadia, Renee M Brielmann, Mario F Neto, Yi-Fan Lin, Cole M Haynes, Richard I Morimoto
In Caenorhabditis elegans, the programmed repression of the heat shock response (HSR) accompanies the transition to reproductive maturity, leaving cells vulnerable to environmental stress and protein aggregation with age. To identify the factors driving this event, we performed an unbiased genetic screen for suppressors of stress resistance and identified the mitochondrial electron transport chain (ETC) as a central regulator of the age-related decline of the HSR and cytosolic proteostasis. Mild downregulation of ETC activity, either by genetic modulation or exposure to mitochondria-targeted xenobiotics, maintained the HSR in adulthood by increasing HSF-1 binding and RNA polymerase II recruitment at HSF-1 target genes...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29117554/downregulation-of-the-apelinergic-axis-accelerates-aging-whereas-its-systemic-restoration-improves-the-mammalian-healthspan
#18
Rahul Rai, Asish K Ghosh, Mesut Eren, Alexander R Mackie, Daniel C Levine, So-Youn Kim, Jonathan Cedernaes, Veronica Ramirez, Daniele Procissi, Layton H Smith, Teresa K Woodruff, Joseph Bass, Douglas E Vaughan
Aging drives the occurrence of numerous diseases, including cardiovascular disease (CVD). Recent studies indicate that blood from young mice reduces age-associated pathologies. However, the "anti-aging" factors in juvenile circulation remain poorly identified. Here, we characterize the role of the apelinergic axis in mammalian aging and identify apelin as an anti-aging factor. The expression of apelin (apln) and its receptor (aplnr) exhibits an age-dependent decline in multiple organs. Reduced apln signaling perturbs organismal homeostasis; mice harboring genetic deficiency of aplnr or apln exhibit enhanced cardiovascular, renal, and reproductive aging...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29107505/system-wide-benefits-of-intermeal-fasting-by-autophagy
#19
Nuria Martinez-Lopez, Elena Tarabra, Miriam Toledo, Marina Garcia-Macia, Srabani Sahu, Luisa Coletto, Ana Batista-Gonzalez, Nir Barzilai, Jeffrey E Pessin, Gary J Schwartz, Sander Kersten, Rajat Singh
Autophagy failure is associated with metabolic insufficiency. Although caloric restriction (CR) extends healthspan, its adherence in humans is poor. We established an isocaloric twice-a-day (ITAD) feeding model wherein ITAD-fed mice consume the same food amount as ad libitum controls but at two short windows early and late in the diurnal cycle. We hypothesized that ITAD feeding will provide two intervals of intermeal fasting per circadian period and induce autophagy. We show that ITAD feeding modifies circadian autophagy and glucose/lipid metabolism that correlate with feeding-driven changes in circulating insulin...
October 24, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29106993/the-role-of-cellular-senescence-in-aging-through-the-prism-of-koch-like-criteria
#20
REVIEW
Hagai Yanai, Vadim E Fraifeld
Since Hayflick's discovery of cellular senescence (CS), a great volume of knowledge in the field has been accumulated and intensively discussed. Here, we attempted to organize the evidence "for" and "against" the hypothesized causal role of CS in aging. For that purpose, we utilized robust Koch-like logical criteria, based on the assumption that some quantitative relationships between the accumulation of senescent cells and aging rate should exist. If so, it could be expected that (i) the "CS load" would be greater in the premature aging phenotype and lesser in longevity phenotype; (ii) CS would promote age-related diseases, and (iii) the interventions that modulate the levels of senescent cells should also modulate health/lifespan...
October 26, 2017: Ageing Research Reviews
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