Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver
Summary
Increasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age‐dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina‐associated domains (LADs) using lamin B1 ChIP‐Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1‐associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors. We also show that Foxa2 ...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Holly Whitton, Larry N. Singh, Marissa A. Patrick, Andrew J. Price, Fernando G. Osorio, Carlos L ópez‐Otín, Irina M. Bochkis Tags: ORIGINAL ARTICLE Source Type: research
The companion dog as a model for human aging and mortality
Summary
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 pa...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Jessica M. Hoffman, Kate E. Creevy, Alexander Franks, Dan G. O'Neill, Daniel E. L. Promislow Tags: ORIGINAL ARTICLE Source Type: research
Aging impacts CD103+CD8+ T cell presence and induction by dendritic cells in the genital tract
Summary
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. Endometrial DCs from post...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Marta Rodriguez ‐Garcia, Jared M. Fortier, Fiona D. Barr, Charles R. Wira Tags: ORIGINAL ARTICLE Source Type: research
Amyloid ‐beta 1‐40 is associated with alterations in NG2+ pericyte population ex vivo and in vitro
Summary
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. We further demonstrate, using in vitro studies, an aggregation‐dependent impac...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Nina Schultz, Kristoffer Br ännström, Elin Byman, Simon Moussaud, Henrietta M. Nielsen, , Anders Olofsson, Malin Wennström Tags: ORIGINAL ARTICLE Source Type: research
The SCN9A channel and plasma membrane depolarization promote cellular senescence through Rb pathway
Summary
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. Important...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: 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 Tags: ORIGINAL ARTICLE Source Type: research
Overexpression of PGC ‐1α in aging muscle enhances a subset of young‐like molecular patterns
Summary
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. Age‐related mtDNA deletion levels were not increa...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Sofia Garcia, Nadee Nissanka, Edson A. Mareco, Susana Rossi, Susana Peralta, Francisca Diaz, Richard L. Rotundo, Robson F. Carvalho, Carlos T. Moraes Tags: ORIGINAL ARTICLE Source Type: research
Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2‐isoprostanes: The CALERIE 2 randomized clinical trial
Summary
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. The primary measure of oxidative status...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Dora Il'yasova, Luigi Fontana, Manjushri Bhapkar, Carl F. Pieper, Ivan Spasojevic, Leanne M. Redman, Sai Krupa Das, Kim M. Huffman, William E. Kraus, Tags: ORIGINAL PAPER Source Type: research
Transcriptomics of aged Drosophila motor neurons reveals a matrix metalloproteinase that impairs motor function
Summary
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‐depende...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Jorge Azpurua, Rebekah E. Mahoney, Benjamin A. Eaton Tags: ORIGINAL ARTICLE Source Type: research
Treatment with the mitochondrial ‐targeted antioxidant peptide SS‐31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice
This study was designed to test the hypothesis that attenuation of mitochondrial oxidative stress may exert beneficial effects on neurovascular coupling responses in aging. To test this hypothesis, 24‐month‐old C57BL/6 mice were treated with a cell‐permeable, mitochondria‐targeted antioxidant peptide (SS‐31; 10 mg kg−1 day−1, i.p.) or vehicle for 2 weeks. Neurovascular coupling was assessed by measuring CBF responses (laser speckle contrast imaging) evoked by contralateral whisker stimulation. We found that neurovascular coupling responses were significantly impaired in aged mice. Treatment with SS–31 s...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: 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 Tags: ORIGINAL ARTICLE Source Type: research
High ‐throughput serum proteomics for the identification of protein biomarkers of mortality in older men
Summary
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 i...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: 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, Tags: ORIGINAL ARTICLE Source Type: research
Aging affects the in vivo regenerative potential of human mesoangioblasts
Summary
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...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Alessio Rotini, Ester Mart ínez‐Sarrà, Robin Duelen, Domiziana Costamagna, Ester Sara Di Filippo, Giorgia Giacomazzi, Hanne Grosemans, Stefania Fulle, Maurilio Sampaolesi Tags: ORIGINAL ARTICLE Source Type: research
Emerging roles of extracellular vesicles in cellular senescence and aging
Summary
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. Senescent cells secrete more EphA2 and DNA via EVs, which can promote cancer cell pro...
Source: Aging Cell - February 1, 2018 Category: Cytology Authors: Masaki Takasugi Tags: REVIEW Source Type: research
Ablation of PPAR γ in subcutaneous fat exacerbates age‐associated obesity and metabolic decline
In conclusion, our study uncovers an essential role for PPARγ in maintaining energy expenditure during the aging process and suggests the possibility of targeting PPARγ to counteract age‐associated metabolic dysfunction. (Source: Aging Cell)
Source: Aging Cell - January 31, 2018 Category: Cytology Authors: Lingyan Xu, Xinran Ma, Narendra Kumar Verma, Dongmei Wang, Oksana Gavrilova, Richard L. Proia, Toren Finkel, Elisabetta Mueller Tags: ORIGINAL ARTICLE Source Type: research
Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults
Aging Cell,Volume 17, Issue 2, April 2018. (Source: Aging Cell)
Source: Aging Cell - January 31, 2018 Category: Cytology Source Type: research
Ablation of PPAR γ in subcutaneous fat exacerbates age‐associated obesity and metabolic decline
Aging Cell,Volume 17, Issue 2, April 2018. (Source: Aging Cell)
Source: Aging Cell - January 31, 2018 Category: Cytology Source Type: research
