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Aging Cell

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https://www.readbyqxmd.com/read/29024417/human-cd8-emra-t-cells-display-a-senescence-associated-secretory-phenotype-regulated-by-p38-mapk
#1
Lauren A Callender, Elizabeth C Carroll, Robert W J Beal, Emma S Chambers, Sussan Nourshargh, Arne N Akbar, Sian M Henson
Cellular senescence is accompanied by a senescence-associated secretory phenotype (SASP). We show here that primary human senescent CD8(+) T cells also display a SASP comprising chemokines, cytokines and extracellular matrix remodelling proteases that are unique to this subset and contribute to age-associated inflammation. We found the CD8(+) CD45RA(+) CD27(-) EMRA subset to be the most heterogeneous, with a population aligning with the naïve T cells and another with a closer association to the effector memory subset...
October 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/29024407/ghrelin-deletion-protects-against-age-associated-hepatic-steatosis-by-downregulating-the-c-ebp%C3%AE-p300-dgat1-pathway
#2
Bobby Guillory, Nicole Jawanmardi, Polina Iakova, Barbara Anderson, Pu Zang, Nikolai A Timchenko, Jose M Garcia
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. NAFLD usually begins as low-grade hepatic steatosis which further progresses in an age-dependent manner to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma in some patients. Ghrelin is a hormone known to promote adiposity in rodents and humans, but its potential role in hepatic steatosis is unknown. We hypothesized that genetic ghrelin deletion will protect against the development of age-related hepatic steatosis...
October 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/29024336/interplay-of-pathogenic-forms-of-human-tau-with-different-autophagic-pathways
#3
Benjamin Caballero, Yipeng Wang, Antonio Diaz, Inmaculada Tasset, Yves Robert Juste, Eva-Maria Mandelkow, Eckhard Mandelkow, Ana Maria Cuervo
Loss of neuronal proteostasis, a common feature of the aging brain, is accelerated in neurodegenerative disorders, including different types of tauopathies. Aberrant turnover of tau, a microtubule-stabilizing protein, contributes to its accumulation and subsequent toxicity in tauopathy patients' brains. A direct toxic effect of pathogenic forms of tau on the proteolytic systems that normally contribute to their turnover has been proposed. In this study, we analyzed the contribution of three different types of autophagy, macroautophagy, chaperone-mediated autophagy, and endosomal microautophagy to the degradation of tau protein variants and tau mutations associated with this age-related disease...
October 12, 2017: Aging Cell
https://www.readbyqxmd.com/read/29024389/in-vivo-properties-of-the-disaggregase-function-of-j-proteins-and-hsc70-in-caenorhabditis-elegans-stress-and-aging
#4
Janine Kirstein, Kristin Arnsburg, Annika Scior, Anna Szlachcic, D Lys Guilbride, Richard I Morimoto, Bernd Bukau, Nadinath B Nillegoda
Protein aggregation is enhanced upon exposure to various stress conditions and aging, which suggests that the quality control machinery regulating protein homeostasis could exhibit varied capacities in different stages of organismal lifespan. Recently, an efficient metazoan disaggregase activity was identified in vitro, which requires the Hsp70 chaperone and Hsp110 nucleotide exchange factor, together with single or cooperating J-protein co-chaperones of classes A and B. Here, we describe how the orthologous Hsp70s and J-protein of Caenorhabditis elegans work together to resolve protein aggregates both in vivo and in vitro to benefit organismal health...
October 10, 2017: Aging Cell
https://www.readbyqxmd.com/read/28994181/age-associated-dysregulation-of-protein-metabolism-in-the-mammalian-oocyte
#5
Francesca E Duncan, Susmita Jasti, Ariel Paulson, John M Kelsh, Barbara Fegley, Jennifer L Gerton
Reproductive aging is characterized by a marked decline in oocyte quality that contributes to infertility, miscarriages, and birth defects. This decline is multifactorial, and the underlying mechanisms are under active investigation. Here, we performed RNA-Seq on individual growing follicles from reproductively young and old mice to identify age-dependent functions in oocytes. This unbiased approach revealed genes involved in cellular processes known to change with age, including mitochondrial function and meiotic chromosome segregation, but also uncovered previously unappreciated categories of genes related to proteostasis and organelles required for protein metabolism...
October 10, 2017: Aging Cell
https://www.readbyqxmd.com/read/28994177/sirtuins-at-the-crossroads-of-stemness-aging-and-cancer
#6
REVIEW
Carol O'Callaghan, Athanassios Vassilopoulos
Sirtuins are stress-responsive proteins that direct various post-translational modifications (PTMs) and as a result, are considered to be master regulators of several cellular processes. They are known to both extend lifespan and regulate spontaneous tumor development. As both aging and cancer are associated with altered stem cell function, the possibility that the involvement of sirtuins in these events is mediated by their roles in stem cells is worthy of investigation. Research to date suggests that the individual sirtuin family members can differentially regulate embryonic, hematopoietic as well as other adult stem cells in a tissue- and cell type-specific context...
October 10, 2017: Aging Cell
https://www.readbyqxmd.com/read/28984064/loss-of-sirt2-leads-to-axonal-degeneration-and-locomotor-disability-associated-with-redox-and-energy-imbalance
#7
Stéphane Fourcade, Laia Morató, Janani Parameswaran, Montserrat Ruiz, Tatiana Ruiz-Cortés, Mariona Jové, Alba Naudí, Paloma Martínez-Redondo, Mara Dierssen, Isidre Ferrer, Francesc Villarroya, Reinald Pamplona, Alejandro Vaquero, Manel Portero-Otín, Aurora Pujol
Sirtuin 2 (SIRT2) is a member of a family of NAD(+) -dependent histone deacetylases (HDAC) that play diverse roles in cellular metabolism and especially for aging process. SIRT2 is located in the nucleus, cytoplasm, and mitochondria, is highly expressed in the central nervous system (CNS), and has been reported to regulate a variety of processes including oxidative stress, genome integrity, and myelination. However, little is known about the role of SIRT2 in the nervous system specifically during aging. Here, we show that middle-aged, 13-month-old mice lacking SIRT2 exhibit locomotor dysfunction due to axonal degeneration, which was not present in young SIRT2 mice...
October 5, 2017: Aging Cell
https://www.readbyqxmd.com/read/28975698/dopamine-d4-receptor-activation-restores-ca1-ltp-in-hippocampal-slices-from-aged-mice
#8
Fangli Guo, Jianhua Zhao, Dandan Zhao, Jiangang Wang, Xiaofang Wang, Zhiwei Feng, Martin Vreugdenhil, Chengbiao Lu
Normal aging is characterized with a decline in hippocampal memory functions that is associated with changes in long-term potentiation (LTP) of the CA3-to-CA1 synapse. Age-related deficit of the dopaminergic system may contribute to impairment of CA1 LTP. Here we assessed how the modulation of CA1 LTP by dopamine is affected by aging and how it is dependent on the Ca(2+) source. In slices from adult mice, the initial slope of the field potential showed strong LTP, but in slices from aged mice LTP was impaired...
October 3, 2017: Aging Cell
https://www.readbyqxmd.com/read/28971552/tor-mediated-regulation-of-metabolism-in-aging
#9
REVIEW
Henri Antikainen, Monica Driscoll, Gal Haspel, Radek Dobrowolski
Cellular metabolism is regulated by the mTOR kinase, a key component of the molecular nutrient sensor pathway that plays a central role in cellular survival and aging. The mTOR pathway promotes protein and lipid synthesis and inhibits autophagy, a process known for its contribution to longevity in several model organisms. The nutrient-sensing pathway is regulated at the lysosomal membrane by a number of proteins for which deficiency triggers widespread aging phenotypes in tested animal models. In response to environmental cues, this recently discovered lysosomal nutrient-sensing complex regulates autophagy transcriptionally through conserved factors, such as the transcription factors TFEB and FOXO, associated with lifespan extension...
October 2, 2017: Aging Cell
https://www.readbyqxmd.com/read/28967703/mir-155-induces-ros-generation-through-downregulation-of-antioxidation-related-genes-in-mesenchymal-stem-cells
#10
Yuta Onodera, Takeshi Teramura, Toshiyuki Takehara, Kayoko Obora, Tatsufumi Mori, Kanji Fukuda
Inflammation-induced reactive oxygen species (ROS) are implicated in cellular dysfunction and an important trigger for aging- or disease-related tissue degeneration. Inflammation-induced ROS in stem cells lead to deterioration of their properties, altering tissue renewal or regeneration. Pathological ROS generation can be induced by multiple steps, and dysfunction of antioxidant systems is a major cause. The identification of the central molecule mediating the above-mentioned processes would pave the way for the development of novel therapeutics for aging, aging-related diseases, or stem cell therapies...
October 2, 2017: Aging Cell
https://www.readbyqxmd.com/read/28963741/micrornas-mir-184-and-let-7-alter-drosophila-metabolism-and-longevity
#11
Christi M Gendron, Scott D Pletcher
MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression associated with many complex biological processes. By comparing miRNA expression between long-lived cohorts of Drosophila melanogaster that were fed a low-nutrient diet with normal-lived control animals fed a high-nutrient diet, we identified miR-184, let-7, miR-125, and miR-100 as candidate miRNAs involved in modulating aging. We found that ubiquitous, adult-specific overexpression of these individual miRNAs led to significant changes in fat metabolism and/or lifespan...
September 29, 2017: Aging Cell
https://www.readbyqxmd.com/read/28961383/caloric-restriction-stabilizes-body-weight-and-accelerates-behavioral-recovery-in-aged-rats-after-focal-ischemia
#12
Ovidiu Ciobanu, Raluca Elena Sandu, Adrian Tudor Balseanu, Alexandra Zavaleanu, Andrei Gresita, Eugen Bogdan Petcu, Adriana Uzoni, Aurel Popa-Wagner
Obesity and hyperinsulinemia are risk factors for stroke. We tested the hypothesis that caloric restriction, which reduces the incidence of age-related obesity and metabolic syndrome, may represent an efficient and cost-effective strategy for preventing stroke and its devastating consequences. To this end, we placed aged, obese Sprague-Dawley aged rats on a calorie-restricted diet for 8 weeks prior to the experimental infarction. Stroke in this animal model caused a progressive decrease in weight that reached a minimum at day 6 for the young rats, and at day 10 for the aged, ad libitum-fed rats...
September 29, 2017: Aging Cell
https://www.readbyqxmd.com/read/28948711/sexually-divergent-dna-methylation-patterns-with-hippocampal-aging
#13
Dustin R Masser, Niran Hadad, Hunter L Porter, Colleen A Mangold, Archana Unnikrishnan, Matthew M Ford, Cory B Giles, Constantin Georgescu, Mikhail G Dozmorov, Jonathan D Wren, Arlan Richardson, David R Stanford, Willard M Freeman
DNA methylation is a central regulator of genome function, and altered methylation patterns are indicative of biological aging and mortality. Age-related cellular, biochemical, and molecular changes in the hippocampus lead to cognitive impairments and greater vulnerability to neurodegenerative disease that varies between the sexes. The role of hippocampal epigenomic changes with aging in these processes is unknown as no genome-wide analyses of age-related methylation changes have considered the factor of sex in a controlled animal model...
September 25, 2017: Aging Cell
https://www.readbyqxmd.com/read/28944611/gene-therapy-with-the-trf1-telomere-gene-rescues-decreased-trf1-levels-with-aging-and-prolongs-mouse-health-span
#14
Aksinya Derevyanko, Kurt Whittemore, Ralph P Schneider, Verónica Jiménez, Fàtima Bosch, Maria A Blasco
The shelterin complex protects telomeres by preventing them from being degraded and recognized as double-strand DNA breaks. TRF1 is an essential component of shelterin, with important roles in telomere protection and telomere replication. We previously showed that TRF1 deficiency in the context of different mouse tissues leads to loss of tissue homeostasis owing to impaired stem cell function. Here, we show that TRF1 levels decrease during organismal aging both in mice and in humans. We further show that increasing TRF1 expression in both adult (1-year-old) and old (2-year-old) mice using gene therapy can delay age-associated pathologies...
September 24, 2017: Aging Cell
https://www.readbyqxmd.com/read/28941045/transthyretin-deposition-promotes-progression-of-osteoarthritis
#15
Tokio Matsuzaki, Yukio Akasaki, Merissa Olmer, Oscar Alvarez-Garcia, Natalia Reixach, Joel N Buxbaum, Martin K Lotz
Deposition of amyloid is a common aging-associated phenomenon in several aging-related diseases. Osteoarthritis (OA) is the most prevalent joint disease, and aging is its major risk factor. Transthyretin (TTR) is an amyloidogenic protein that is deposited in aging and OA-affected human cartilage and promotes inflammatory and catabolic responses in cultured chondrocytes. Here, we investigated the role of TTR in vivo using transgenic mice overexpressing wild-type human TTR (hTTR-TG). Although TTR protein was detected in cartilage in hTTR-TG mice, the TTR transgene was highly overexpressed in liver, but not in chondrocytes...
September 22, 2017: Aging Cell
https://www.readbyqxmd.com/read/28940623/genetic-interaction-with-temperature-is-an-important-determinant-of-nematode-longevity
#16
Hillary Miller, Marissa Fletcher, Melissa Primitivo, Alison Leonard, George L Sutphin, Nicholas Rintala, Matt Kaeberlein, Scott F Leiser
As in other poikilotherms, longevity in C. elegans varies inversely with temperature; worms are longer-lived at lower temperatures. While this observation may seem intuitive based on thermodynamics, the molecular and genetic basis for this phenomenon is not well understood. Several recent reports have argued that lifespan changes across temperatures are genetically controlled by temperature-specific gene regulation. Here, we provide data that both corroborate those studies and suggest that temperature-specific longevity is more the rule than the exception...
September 21, 2017: Aging Cell
https://www.readbyqxmd.com/read/28921841/in-a-randomized-trial-in-prostate-cancer-patients-dietary-protein-restriction-modifies-markers-of-leptin-and-insulin-signaling-in-plasma-extracellular-vesicles
#17
Erez Eitan, Valeria Tosti, Caitlin N Suire, Edda Cava, Sean Berkowitz, Beatrice Bertozzi, Sophia M Raefsky, Nicola Veronese, Ryan Spangler, Francesco Spelta, Maja Mustapic, Dimitrios Kapogiannis, Mark P Mattson, Luigi Fontana
Obesity, metabolic syndrome, and hyperleptinemia are associated with aging and age-associated diseases including prostate cancer. One experimental approach to inhibit tumor growth is to reduce dietary protein intake and hence levels of circulating amino acids. Dietary protein restriction (PR) increases insulin sensitivity and suppresses prostate cancer cell tumor growth in animal models, providing a rationale for clinical trials. We sought to demonstrate that biomarkers derived from plasma extracellular vesicles (EVs) reflect systemic leptin and insulin signaling and respond to dietary interventions...
September 17, 2017: Aging Cell
https://www.readbyqxmd.com/read/28891115/deficiency-of-ccaat-enhancer-binding-protein-homologous-protein-chop-prevents-diet-induced-aortic-valve-calcification-in%C3%A2-vivo
#18
Zhejun Cai, Baoqing Liu, Jia Wei, Zurong Fu, Yidong Wang, Yaping Wang, Jian Shen, Liangliang Jia, Shengan Su, Xiaoya Wang, Xiaoping Lin, Han Chen, Fei Li, Jian'an Wang, Meixiang Xiang
Aortic valve (AoV) calcification is common in aged populations. Its subsequent aortic stenosis has been linked with increased morbidity, but still has no effective pharmacological intervention. Our previous data show endoplasmic reticulum (ER) stress is involved in AoV calcification. Here, we investigated whether deficiency of ER stress downstream effector CCAAT/enhancer-binding protein homology protein (CHOP) may prevent development of AoV calcification. AoV calcification was evaluated in Apoe(-/-) mice (n = 10) or in mice with dual deficiencies of ApoE and CHOP (Apoe(-/-) CHOP(-/-) , n = 10) fed with Western diet for 24 weeks...
September 10, 2017: Aging Cell
https://www.readbyqxmd.com/read/28884514/estrogenic-regulation-of-skeletal-muscle-proteome-a-study-of-premenopausal-women-and-postmenopausal-mz-cotwins-discordant-for-hormonal-therapy
#19
Eija K Laakkonen, Rabah Soliymani, Sira Karvinen, Jaakko Kaprio, Urho M Kujala, Marc Baumann, Sarianna Sipilä, Vuokko Kovanen, Maciej Lalowski
Female middle age is characterized by a decline in skeletal muscle mass and performance, predisposing women to sarcopenia, functional limitations, and metabolic dysfunction as they age. Menopausal loss of ovarian function leading to low circulating level of 17β-estradiol has been suggested as a contributing factor to aging-related muscle deterioration. However, the underlying molecular mechanisms remain largely unknown and thus far androgens have been considered as a major anabolic hormone for skeletal muscle...
September 7, 2017: Aging Cell
https://www.readbyqxmd.com/read/28857490/the-acceleration-of-reproductive-aging-in-nrg1-flox-flox-cyp19-cre-female-mice
#20
Takashi Umehara, Tomoko Kawai, Ikko Kawashima, Katsuhiro Tanaka, Satoshi Okuda, Hiroya Kitasaka, JoAnne S Richards, Masayuki Shimada
Irregular menstrual cycles, reduced responses to exogenous hormonal treatments, and altered endocrine profiles (high FSH/high LH/low AMH) are observed in women with increasing age before menopause. In this study, because the granulosa cell-specific Nrg1 knockout mice (gcNrg1KO) presented ovarian and endocrine phenotypes similar to older women, we sought to understand the mechanisms of ovarian aging and to develop a new strategy for improving fertility in older women prior to menopause. In the ovary of 6-month-old gcNrg1KO mice, follicular development was blocked in bilayer secondary follicles and heterogeneous cells accumulated in ovarian stroma...
August 31, 2017: Aging Cell
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