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Aging Cell

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https://www.readbyqxmd.com/read/29457329/the-companion-dog-as-a-model-for-human-aging-and-mortality
#1
Jessica M Hoffman, Kate E Creevy, Alexander Franks, Dan G O'Neill, Daniel E L Promislow
Around the world, human populations have experienced large increases in average lifespan over the last 150 years, and while individuals are living longer, they are spending more years of life with multiple chronic morbidities. Researchers have used numerous laboratory animal models to understand the biological and environmental factors that influence aging, morbidity, and longevity. However, the most commonly studied animal species, laboratory mice and rats, do not experience environmental conditions similar to those to which humans are exposed, nor do we often diagnose them with many of the naturally occurring pathologies seen in humans...
February 19, 2018: Aging Cell
https://www.readbyqxmd.com/read/29455474/aging-impacts-cd103-cd8-t-cell-presence-and-induction-by-dendritic-cells-in-the-genital-tract
#2
Marta Rodriguez-Garcia, Jared M Fortier, Fiona D Barr, Charles R Wira
As women age, susceptibility to systemic and genital infections increases. Tissue-resident memory T cells (TRMs) are CD103+ CD8+ long-lived lymphocytes that provide critical mucosal immune protection. Mucosal dendritic cells (DCs) are known to induce CD103 expression on CD8+ T cells. While CD103+ CD8+ T cells are found throughout the female reproductive tract (FRT), the extent to which aging impacts their presence and induction by DCs remains unknown. Using hysterectomy tissues, we found that endometrial CD103+ CD8+ T cells were increased in postmenopausal compared to premenopausal women...
February 18, 2018: Aging Cell
https://www.readbyqxmd.com/read/29453790/amyloid-beta-1-40-is-associated-with-alterations-in-ng2-pericyte-population-ex-vivo-and-in-vitro
#3
Nina Schultz, Kristoffer Brännström, Elin Byman, Simon Moussaud, Henrietta M Nielsen, Anders Olofsson, Malin Wennström
The population of brain pericytes, a cell type important for vessel stability and blood brain barrier function, has recently been shown altered in patients with Alzheimer's disease (AD). The underlying reason for this alteration is not fully understood, but progressive accumulation of the AD characteristic peptide amyloid-beta (Aβ) has been suggested as a potential culprit. In the current study, we show reduced number of hippocampal NG2+ pericytes and an association between NG2+ pericyte numbers and Aβ1-40 levels in AD patients...
February 17, 2018: Aging Cell
https://www.readbyqxmd.com/read/29446526/the-scn9a-channel-and-plasma-membrane-depolarization-promote-cellular-senescence-through-rb-pathway
#4
Marine Warnier, Jean-Michel Flaman, Christophe Chouabe, Clotilde Wiel, Baptiste Gras, Audrey Griveau, Elena Blanc, Jean-Philippe Foy, Pauline Mathot, Pierre Saintigny, Fabien Van Coppenolle, David Vindrieux, Nadine Martin, David Bernard
Oncogenic signals lead to premature senescence in normal human cells causing a proliferation arrest and the elimination of these defective cells by immune cells. Oncogene-induced senescence (OIS) prevents aberrant cell division and tumor initiation. In order to identify new regulators of OIS, we performed a loss-of-function genetic screen and identified that the loss of SCN9A allowed cells to escape from OIS. The expression of this sodium channel increased in senescent cells during OIS. This upregulation was mediated by NF-κB transcription factors, which are well-known regulators of senescence...
February 15, 2018: Aging Cell
https://www.readbyqxmd.com/read/29427317/overexpression-of-pgc-1%C3%AE-in-aging-muscle-enhances-a-subset-of-young-like-molecular-patterns
#5
Sofia Garcia, Nadee Nissanka, Edson A Mareco, Susana Rossi, Susana Peralta, Francisca Diaz, Richard L Rotundo, Robson F Carvalho, Carlos T Moraes
PGC-1α is a transcriptional co-activator known as the master regulator of mitochondrial biogenesis. Its control of metabolism has been suggested to exert critical influence in the aging process. We have aged mice overexpressing PGC-1α in skeletal muscle to determine whether the transcriptional changes reflected a pattern of expression observed in younger muscle. Analyses of muscle proteins showed that Pax7 and several autophagy markers were increased. In general, the steady-state levels of several muscle proteins resembled that of muscle from young mice...
February 10, 2018: Aging Cell
https://www.readbyqxmd.com/read/29424490/effects-of-2%C3%A2-years-of-caloric-restriction-on-oxidative-status-assessed-by-urinary-f2-isoprostanes-the-calerie-2-randomized-clinical-trial
#6
Dora Il'yasova, Luigi Fontana, Manjushri Bhapkar, Carl F Pieper, Ivan Spasojevic, Leanne M Redman, Sai Krupa Das, Kim M Huffman, William E Kraus
Calorie restriction (CR) without malnutrition slows aging in animal models. Oxidative stress reduction was proposed to mediate CR effects. CR effect on urinary F2-isoprostanes, validated oxidative stress markers, was assessed in CALERIE, a two-year randomized controlled trial. Healthy volunteers (n = 218) were randomized to prescribed 25% CR (n = 143) or ad libitum control (AL, n = 75) stratifying the randomization schedule by site, sex, and BMI. F2-isoprostanes were quantified using LC-MS/MS in morning, fasted urine specimens at baseline, at 12 and 24 months...
February 9, 2018: Aging Cell
https://www.readbyqxmd.com/read/29411505/transcriptomics-of-aged-drosophila-motor-neurons-reveals-a-matrix-metalloproteinase-that-impairs-motor-function
#7
Jorge Azpurua, Rebekah E Mahoney, Benjamin A Eaton
The neuromuscular junction (NMJ) is responsible for transforming nervous system signals into motor behavior and locomotion. In the fruit fly Drosophila melanogaster, an age-dependent decline in motor function occurs, analogous to the decline experienced in mice, humans, and other mammals. The molecular and cellular underpinnings of this decline are still poorly understood. By specifically profiling the transcriptome of Drosophila motor neurons across age using custom microarrays, we found that the expression of the matrix metalloproteinase 1 (dMMP1) gene reproducibly increased in motor neurons in an age-dependent manner...
February 7, 2018: Aging Cell
https://www.readbyqxmd.com/read/29405550/treatment-with-the-mitochondrial-targeted-antioxidant-peptide-ss-31-rescues-neurovascular-coupling-responses-and-cerebrovascular-endothelial-function-and-improves-cognition-in-aged-mice
#8
Stefano Tarantini, Noa M Valcarcel-Ares, Andriy Yabluchanskiy, Gabor A Fulop, Peter Hertelendy, Tripti Gautam, Eszter Farkas, Aleksandra Perz, Peter S Rabinovitch, William E Sonntag, Anna Csiszar, Zoltan Ungvari
Moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling has an essential role in maintenance of healthy cognitive function. In advanced age, increased oxidative stress and cerebromicrovascular endothelial dysfunction impair neurovascular coupling, likely contributing to age-related decline of higher cortical functions. There is increasing evidence showing that mitochondrial oxidative stress plays a critical role in a range of age-related cellular impairments, but its role in neurovascular uncoupling remains unexplored...
February 6, 2018: Aging Cell
https://www.readbyqxmd.com/read/29405587/smurf2-regulates-stability-and-the-autophagic-lysosomal-turnover-of-lamin-a-and-its-disease-associated-form-progerin
#9
Aurora Paola Borroni, Andrea Emanuelli, Pooja Anil Shah, Nataša Ilić, Liat Apel-Sarid, Biagio Paolini, Dhanoop Manikoth Ayyathan, Praveen Koganti, Gal Levy-Cohen, Michael Blank
A-lamins, encoded by the LMNA gene, are major structural components of the nuclear lamina coordinating essential cellular processes. Mutations in the LMNA gene and/or alterations in its expression levels have been linked to a distinct subset of human disorders, collectively known as laminopathies, and to cancer. Mechanisms regulating A-lamins are mostly obscure. Here, we identified E3 ubiquitin ligase Smurf2 as a physiological regulator of lamin A and its disease-associated mutant form progerin (LAΔ50), whose expression underlies the development of Hutchinson-Gilford progeria syndrome (HGPS), a devastating premature aging syndrome...
February 5, 2018: Aging Cell
https://www.readbyqxmd.com/read/29399943/high-throughput-serum-proteomics-for-the-identification-of-protein-biomarkers-of-mortality-in-older-men
#10
Eric S Orwoll, Jack Wiedrick, Jon Jacobs, Erin S Baker, Paul Piehowski, Vladislav Petyuk, Yuqian Gao, Tujin Shi, Richard D Smith, Douglas C Bauer, Steven R Cummings, Carrie M Nielson, Jodi Lapidus
The biological perturbations associated with incident mortality are not well elucidated, and there are limited biomarkers for the prediction of mortality. We used a novel high-throughput proteomics approach to identify serum peptides and proteins associated with 5-year mortality in community-dwelling men age ≥65 years who participated in a longitudinal observational study of musculoskeletal aging (Osteoporotic Fractures in Men: MrOS). In a discovery phase, serum specimens collected at baseline in 2473 men were analyzed using liquid chromatography-ion mobility-mass spectrometry, and incident mortality in the subsequent 5 years was ascertained by tri-annual questionnaire...
February 5, 2018: Aging Cell
https://www.readbyqxmd.com/read/29397579/%C3%AE-motor-neurons-are-spared-from-aging-while-their-synaptic-inputs-degenerate-in-monkeys-and-mice
#11
Nicholas Maxwell, Ryan W Castro, Natalia M Sutherland, Kelli L Vaughan, Mark D Szarowicz, Rafael de Cabo, Julie A Mattison, Gregorio Valdez
Motor function deteriorates with advancing age, increasing the risk of adverse health outcomes. While it is well established that skeletal muscles and neuromuscular junctions (NMJs) degenerate with increasing age, the effect of aging on α-motor neurons and their innervating synaptic inputs remains largely unknown. In this study, we examined the soma of α-motor neurons and innervating synaptic inputs in the spinal cord of aged rhesus monkeys and mice, two species with vastly different lifespans. We found that, in both species, α-motor neurons retain their soma size despite an accumulation of large amounts of cellular waste or lipofuscin...
February 4, 2018: Aging Cell
https://www.readbyqxmd.com/read/29397577/aging-affects-the-in%C3%A2-vivo-regenerative-potential-of-human-mesoangioblasts
#12
Alessio Rotini, Ester Martínez-Sarrà, Robin Duelen, Domiziana Costamagna, Ester Sara Di Filippo, Giorgia Giacomazzi, Hanne Grosemans, Stefania Fulle, Maurilio Sampaolesi
Sarcopenia is the age-related loss of muscle mass, strength, and function. Although the role of human satellite cells (SCs) as adult skeletal muscle stem cells has been deeply investigated, little is known about the impact of aging on muscle interstitial stem cells. Here, we isolated the non-SC CD56- fraction from human muscle biopsies of young and elderly subjects. The elderly interstitial cell population contained a higher number of CD15+ and PDGFRα+ cells when compared to young samples. In addition, we found that the CD56- /ALP+ cells were well represented as a multipotent stem cell population inside the CD56- fraction...
February 4, 2018: Aging Cell
https://www.readbyqxmd.com/read/29392820/emerging-roles-of-extracellular-vesicles-in-cellular-senescence-and-aging
#13
REVIEW
Masaki Takasugi
Cellular senescence is a cellular program that prevents the proliferation of cells at risk of neoplastic transformation. On the other hand, age-related accumulation of senescent cells promotes aging at least partially due to the senescence-associated secretory phenotype, whereby cells secrete high levels of inflammatory cytokines, chemokines, and matrix metalloproteinases. Emerging evidence, however, indicates that extracellular vesicles (EVs) are important mediators of the effects of senescent cells on their microenvironment...
February 1, 2018: Aging Cell
https://www.readbyqxmd.com/read/29383869/metformin-regulates-metabolic-and-nonmetabolic-pathways-in-skeletal-muscle-and-subcutaneous-adipose-tissues-of-older-adults
#14
Ameya S Kulkarni, Erika F Brutsaert, Valentin Anghel, Kehao Zhang, Noah Bloomgarden, Michael Pollak, Jessica C Mar, Meredith Hawkins, Jill P Crandall, Nir Barzilai
Administration of metformin increases healthspan and lifespan in model systems, and evidence from clinical trials and observational studies suggests that metformin delays a variety of age-related morbidities. Although metformin has been shown to modulate multiple biological pathways at the cellular level, these pleiotropic effects of metformin on the biology of human aging have not been studied. We studied ~70-year-old participants (n = 14) in a randomized, double-blind, placebo-controlled, crossover trial in which they were treated with 6 weeks each of metformin and placebo...
January 31, 2018: Aging Cell
https://www.readbyqxmd.com/read/29383825/ablation-of-ppar%C3%AE-in-subcutaneous-fat-exacerbates-age-associated-obesity-and-metabolic-decline
#15
Lingyan Xu, Xinran Ma, Narendra Kumar Verma, Dongmei Wang, Oksana Gavrilova, Richard L Proia, Toren Finkel, Elisabetta Mueller
It is well established that aging is associated with metabolic dysfunction such as increased adiposity and impaired energy dissipation; however, the transcriptional mechanisms regulating energy balance during late life stages have not yet been fully elucidated. Here, we show that ablation of the nuclear receptor PPARγ specifically in inguinal fat tissue in aging mice is associated with increased fat tissue expansion and insulin resistance. These metabolic effects are accompanied by decreased thermogenesis, reduced levels of brown fat genes, and browning of subcutaneous adipose tissue...
January 31, 2018: Aging Cell
https://www.readbyqxmd.com/read/29383832/long-lasting-pathological-consequences-of-overexpression-induced-%C3%AE-synuclein-spreading-in-the-rat-brain
#16
Raffaella Rusconi, Ayse Ulusoy, Helia Aboutalebi, Donato A Di Monte
Increased expression of α-synuclein can initiate its long-distance brain transfer, representing a potential mechanism for pathology spreading in age-related synucleinopathies, such as Parkinson's disease. In this study, the effects of overexpression-induced α-synuclein transfer were assessed over a 1-year period after injection of viral vectors carrying human α-synuclein DNA into the rat vagus nerve. This treatment causes targeted overexpression within neurons in the dorsal medulla oblongata and subsequent diffusion of the exogenous protein toward more rostral brain regions...
January 30, 2018: Aging Cell
https://www.readbyqxmd.com/read/29363258/atf3-represses-pink1-gene-transcription-in-lung-epithelial-cells-to-control-mitochondrial-homeostasis
#17
Marta Bueno, Judith Brands, Lauren Voltz, Kaitlin Fiedler, Brenton Mays, Claudette St Croix, John Sembrat, Rama K Mallampalli, Mauricio Rojas, Ana L Mora
PINK1 (PTEN-induced putative kinase 1) is a key regulator of mitochondrial homeostasis that is relatively depleted in aging lungs and in lung epithelial cells from patients with idiopathic pulmonary fibrosis (IPF), a disease linked with aging. Impaired PINK1 expression and accumulation of damaged mitochondria in lung epithelial cells from fibrotic lungs were associated with the presence of ER stress. Here, we show that ATF3 (activating transcription factor 3), a member of the integrated stress response (ISR), negatively regulates transcription of the PINK1 gene...
January 24, 2018: Aging Cell
https://www.readbyqxmd.com/read/29356348/skeletal-muscle-ex%C3%A2-vivo-mitochondrial-respiration-parallels-decline-in%C3%A2-vivo-oxidative-capacity-cardiorespiratory-fitness-and-muscle-strength-the-baltimore-longitudinal-study-of-aging
#18
Marta Gonzalez-Freire, Paul Scalzo, Jarod D'Agostino, Zenobia A Moore, Alberto Diaz-Ruiz, Elisa Fabbri, Ariel Zane, Brian Chen, Kevin G Becker, Elin Lehrmann, Linda Zukley, Chee W Chia, Toshiko Tanaka, Paul M Coen, Michel Bernier, Rafael de Cabo, Luigi Ferrucci
Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline comes from studies that assessed mitochondrial function indirectly, and the impact of such deterioration with respect to physical function has not been clearly delineated. We hypothesized that mitochondrial respiration in permeabilized human muscle fibers declines with age and correlates with phosphocreatine postexercise recovery rate (kPCr), muscle performance, and aerobic fitness. Mitochondrial respiration was assessed by high-resolution respirometry in saponin-permeabilized fibers from vastus lateralis muscle biopsies of 38 participants from the Baltimore Longitudinal Study of Aging (BLSA; 21 men, age 24-91 years) who also had available measures of peak oxygen consumption (VO2max ) from treadmill tests, gait speed in different tasks, 31 P magnetic resonance spectroscopy, isokinetic knee extension, and grip strength...
January 21, 2018: Aging Cell
https://www.readbyqxmd.com/read/29349889/t-cell-immunoglobulin-and-itim-domain-contributes-to-cd8-t-cell-immunosenescence
#19
Yangzi Song, Beibei Wang, Rui Song, Yu Hao, Di Wang, Yuxin Li, Yu Jiang, Ling Xu, Yaluan Ma, Hong Zheng, Yaxian Kong, Hui Zeng
Aging is associated with immune dysfunction, especially T-cell defects, which result in increased susceptibility to various diseases. Previous studies showed that T cells from aged mice express multiple inhibitory receptors, providing evidence of the relationship between T-cell exhaustion and T-cell senescence. In this study, we showed that T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), a novel co-inhibitory receptor, was upregulated in CD8+ T cells of elderly adults...
January 19, 2018: Aging Cell
https://www.readbyqxmd.com/read/29336105/senescence-chips-for-ultrahigh-throughput-isolation-and-removal-of-senescent-cells
#20
Yuchao Chen, Pan Mao, Antoine M Snijders, Daojing Wang
Cellular senescence plays an important role in organismal aging and age-related diseases. However, it is challenging to isolate low numbers of senescent cells from small volumes of biofluids for downstream analysis. Furthermore, there is no technology that could selectively remove senescent cells in a high-throughput manner. In this work, we developed a novel microfluidic chip platform, termed senescence chip, for ultrahigh-throughput isolation and removal of senescent cells. The core component of our senescence chip is a slanted and tunable 3D micropillar array with a variety of shutters in the vertical direction for rapid cell sieving, taking advantage of the characteristic cell size increase during cellular senescence...
January 16, 2018: Aging Cell
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