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Transthyretin deposition promotes progression of osteoarthritis
Summary 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, b...
Source: Aging Cell - September 23, 2017 Category: Cytology Authors: Tokio Matsuzaki, Yukio Akasaki, Merissa Olmer, Oscar Alvarez ‐Garcia, Natalia Reixach, Joel N. Buxbaum, Martin K. Lotz Tags: Original Article Source Type: research

Genetic interaction with temperature is an important determinant of nematode longevity
Summary 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. By measuring the lifespans of worms with single ...
Source: Aging Cell - September 22, 2017 Category: Cytology Authors: Hillary Miller, Marissa Fletcher, Melissa Primitivo, Alison Leonard, George L. Sutphin, Nicholas Rintala, Matt Kaeberlein, Scott F. Leiser Tags: Short Take Source Type: research

In a randomized trial in prostate cancer patients, dietary protein restriction modifies markers of leptin and insulin signaling in plasma extracellular vesicles
Summary 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. We studied p...
Source: Aging Cell - September 18, 2017 Category: Cytology Authors: 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 Tags: Short Take Source Type: research

Issue Information
(Source: Aging Cell)
Source: Aging Cell - September 12, 2017 Category: Cytology Tags: Issue Information Source Type: research

Hyperphosphatemia induces senescence in human endothelial cells by increasing endothelin ‐1 production
Summary Hyperphosphatemia is related to some pathologies, affecting vascular cell behavior. This work analyzes whether high concentration of extracellular phosphate induces endothelial senescence through up‐regulation of endothelin‐1 (ET‐1), exploring the mechanisms involved. The phosphate donor β‐glycerophosphate (BGP) in human endothelial cells increased ET‐1 production, endothelin‐converting enzyme‐1 (ECE‐1) protein, and mRNA expression, which depend on the AP‐1 activation through ROS production. In parallel, BGP also induced endothelial senescence by increasing p16 expression and the senescence...
Source: Aging Cell - August 31, 2017 Category: Cytology Authors: Gemma Olmos, Patricia Mart ínez‐Miguel, Elena Alcalde‐Estevez, Diana Medrano, Patricia Sosa, Leocadio Rodríguez‐Mañas, Manuel Naves‐Diaz, Diego Rodríguez‐Puyol, María Piedad Ruiz‐Torres, Susana López‐Ongil Tags: Original Article Source Type: research

Opposing effects on cardiac function by calorie restriction in different ‐aged mice
Summary Calorie restriction (CR) increases average and maximum lifespan and exhibits an apparent beneficial impact on age‐related diseases. Several studies have shown that CR initiated either in middle or old age could improve ischemic tolerance and rejuvenate the aging heart; however, the data are not uniform when initiated in young. The accurate time to initiate CR providing maximum benefits for cardiac remodeling and function during aging remains unclear. Thus, whether a similar degree of CR initiated in mice of different ages could exert a similar effect on myocardial protection was investigated in this study. C57BL/...
Source: Aging Cell - August 11, 2017 Category: Cytology Authors: Yunlu Sheng, Shan Lv, Min Huang, Yifan Lv, Jing Yu, Juan Liu, Tingting Tang, Hanmei Qi, Wenjuan Di, Guoxian Ding Tags: Original Article Source Type: research

In vivo imaging reveals mitophagy independence in the maintenance of axonal mitochondria during normal aging
Summary Mitophagy is thought to be a critical mitochondrial quality control mechanism in neurons and has been extensively studied in neurological disorders such as Parkinson's disease. However, little is known about how mitochondria are maintained in the lengthy neuronal axons in the context of physiological aging. Here, we utilized the unique Drosophila wing nerve model and in vivo imaging to rigorously profile changes in axonal mitochondria during aging. We revealed that mitochondria became fragmented and accumulated in aged axons. However, lack of Pink1 or Parkin did not lead to the accumulation of axonal mitochond...
Source: Aging Cell - August 7, 2017 Category: Cytology Authors: Xu Cao, Haiqiong Wang, Zhao Wang, Qingyao Wang, Shuang Zhang, Yuanping Deng, Yanshan Fang Tags: Original Article Source Type: research

The ω‐3 fatty acid α‐linolenic acid extends Caenorhabditis elegans lifespan via NHR‐49/PPARα and oxidation to oxylipins
Summary The dietary intake of ω‐3 polyunsaturated fatty acids has been linked to a reduction in the incidence of aging‐associated disease including cardiovascular disease and stroke. Additionally, long‐lived Caenorhabditis elegans glp‐1 germ line‐less mutant animals show a number of changes in lipid metabolism including the increased production of the ω‐3 fatty acid, α‐linolenic acid (ALA). Here, we show that the treatment of C. elegans with ALA produces a dose‐dependent increase in lifespan. The increased longevity of the glp‐1 mutant animals is known to be dependent on both the NH...
Source: Aging Cell - August 3, 2017 Category: Cytology Authors: Wenbo Qi, Gloria E. Gutierrez, Xiaoli Gao, Hong Dixon, Joe A. McDonough, Ann M. Marini, Alfred L. Fisher Tags: Original Article Source Type: research

Deficiency of CCAAT/enhancer ‐binding protein homologous protein (CHOP) prevents diet‐induced aortic valve calcification in vivo
Summary 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&minus...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: 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 Tags: Original Article Source Type: research

Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and postmenopausal MZ cotwins discordant for hormonal therapy
Summary 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. We utilized muscle samples from 24 pre‐ and postmenopausal women to establish proteome‐wide p...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Eija K. Laakkonen, Rabah Soliymani, Sira Karvinen, Jaakko Kaprio, Urho M. Kujala, Marc Baumann, Sarianna Sipil ä, Vuokko Kovanen, Maciej Lalowski Tags: Original Article Source Type: research

The acceleration of reproductive aging in Nrg1flox/flox;Cyp19 ‐Cre female mice
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. The heterogeneous cells in ovarian stroma were distinguished as two different types: (i) the LH receptor‐positive endocrine cells and (ii) actin‐rich fibrotic cell...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Takashi Umehara, Tomoko Kawai, Ikko Kawashima, Katsuhiro Tanaka, Satoshi Okuda, Hiroya Kitasaka, JoAnne S. Richards, Masayuki Shimada Tags: Original Article Source Type: research

Can FSH influence longevity?
Summary It was recently reported that the extragonadal actions of follicle‐stimulating hormone (FSH) include regulation of brown and white adipose tissue function and thermogenesis. Based on these findings and on our evidence for reduced FSH levels and enhanced thermogenesis in long‐lived growth hormone (GH)‐deficient mice and GH‐resistant mice, we suggest that FSH may have a role in the control of aging and longevity. We speculate that alterations in FSH secretion may represent one of the mechanisms of trade‐offs between reproduction and aging. (Source: Aging Cell)
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Andrzej Bartke Tags: Commentary Source Type: research

Wide ‐scale comparative analysis of longevity genes and interventions
Summary Hundreds of genes, when manipulated, affect the lifespan of model organisms (yeast, worm, fruit fly, and mouse) and thus can be defined as longevity‐associated genes (LAGs). A major challenge is to determine whether these LAGs are model‐specific or may play a universal role as longevity regulators across diverse taxa. A wide‐scale comparative analysis of the 1805 known LAGs across 205 species revealed that (i) LAG orthologs are substantially overrepresented, from bacteria to mammals, compared to the entire genomes or interactomes, and this was especially noted for essential LAGs; (ii) the effects on lifespan,...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Hagai Yanai, Arie Budovsky, Thomer Barzilay, Robi Tacutu, Vadim E. Fraifeld Tags: Original Article Source Type: research

Sex differences in lifespan extension with acarbose and 17 ‐α estradiol: gonadal hormones underlie male‐specific improvements in glucose tolerance and mTORC2 signaling
Summary Interventions that extend lifespan in mice can show substantial sexual dimorphism. Here, we show that male‐specific lifespan extension with two pharmacological treatments, acarbose (ACA) and 17‐α estradiol (17aE2), is associated, in males only, with increased insulin sensitivity and improved glucose tolerance. Females, which show either smaller (ACA) or no lifespan extension (17aE2), do not derive these metabolic benefits from drug treatment. We find that these male‐specific metabolic improvements are associated with enhanced hepatic mTORC2 signaling, increased Akt activity, and phosphorylation of FOXO1...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Michael Garratt, Brian Bower, Gonzalo G. Garcia, Richard A. Miller Tags: Original Article Source Type: research

In aged primary T cells, mitochondrial stress contributes to telomere attrition measured by a novel imaging flow cytometry assay
Summary The decline of the immune system with age known as immune senescence contributes to inefficient pathogen clearance and is a key risk factor for many aged‐related diseases. However, reversing or halting immune aging requires more knowledge about the cell biology of senescence in immune cells. Telomere shortening, low autophagy and mitochondrial dysfunction have been shown to underpin cell senescence. While autophagy has been found to control mitochondrial damage, no link has been made to telomere attrition. In contrast, mitochondrial stress can contribute to telomere attrition and vice versa. Whereas this link has...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Sharon Lesley Sanderson, Anna Katharina Simon Tags: Original Article Source Type: research

A multimethod computational simulation approach for investigating mitochondrial dynamics and dysfunction in degenerative aging
Summary Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by inclu...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Timothy E. Hoffman, Katherine J. Barnett, Lyle Wallis, William H. Hanneman Tags: Original Article Source Type: research

The valosin ‐containing protein is a novel repressor of cardiomyocyte hypertrophy induced by pressure overload
In conclusion, VCP acts as a novel repressor that is able to prevent cardiomyocyte hypertrophy from pressure overload by modulating the mTORC1 signaling pathway. (Source: Aging Cell)
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Ning Zhou, Ben Ma, Shaunrick Stoll, Tristan T. Hays, Hongyu Qiu Tags: Original Article Source Type: research

Reduced expression of PMCA1 is associated with increased blood pressure with age which is preceded by remodelling of resistance arteries
Summary Hypertension is a well‐established risk factor for adverse cardiovascular events, and older age is a risk factor for the development of hypertension. Genomewide association studies have linked ATP2B1, the gene for the plasma membrane calcium ATPase 1 (PMCA1), to blood pressure (BP) and hypertension. Here, we present the effects of reduction in the expression of PMCA1 on BP and small artery structure and function when combined with advancing age. Heterozygous PMCA1 null mice (PMCA1Ht) were generated and conscious BP was measured at 6 to 18 months of age. Passive and active properties of isolated small mesente...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Robert Little, Min Zi, Sally K. Hammad, Loan Nguyen, Alexandra Njegic, Sathishkumar Kurusamy, Sukhpal Prehar, Angel L. Armesilla, Ludwig Neyses, Clare Austin, Elizabeth J. Cartwright Tags: Original Article Source Type: research

Autophagy in stem cell aging
Summary Aging is responsible for changes in mammalian tissues that result in an imbalance to tissue homeostasis and a decline in the regeneration capacity of organs due to stem cell exhaustion. Autophagy is a constitutive pathway necessary to degrade damaged organelles and protein aggregates. Autophagy is one of the hallmarks of aging, which involves a decline in the number and functionality of stem cells. Recent studies show that stem cells require autophagy to get rid of cellular waste produced during the quiescent stage. In particular, two independent studies in muscle and hematopoietic stem cells demonstrate the releva...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Miren Revuelta, Ander Matheu Tags: Commentary Source Type: research

Dyrk1 inhibition improves Alzheimer's disease ‐like pathology
Summary There is an urgent need for the development of new therapeutic strategies for Alzheimer's disease (AD). The dual‐specificity tyrosine phosphorylation‐regulated kinase‐1A (Dyrk1a) is a protein kinase that phosphorylates the amyloid precursor protein (APP) and tau and thus represents a link between two key proteins involved in AD pathogenesis. Furthermore, Dyrk1a is upregulated in postmortem human brains, and high levels of Dyrk1a are associated with mental retardation. Here, we sought to determine the effects of Dyrk1 inhibition on AD‐like pathology developed by 3xTg‐AD mice, a widely used animal model of ...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Caterina Branca, Darren M. Shaw, Ramona Belfiore, Vijay Gokhale, Arthur Y. Shaw, Christopher Foley, Breland Smith, Christopher Hulme, Travis Dunckley, Bessie Meechoovet, Antonella Caccamo, Salvatore Oddo Tags: Original Article Source Type: research

HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer's disease
In conclusion, our results indicate that HDAC3 negatively regulates spatial memory in APP/PS1 mice and HDAC3 inhibition might represent a potential therapy for the treatment of AD. (Source: Aging Cell)
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Xiaolei Zhu, Sulei Wang, Linjie Yu, Jiali Jin, Xing Ye, Yi Liu, Yun Xu Tags: Original Article Source Type: research

Evidence for reduced neurogenesis in the aging human hippocampus despite stable stem cell markers
Summary Reduced neurogenesis in the aging mammalian hippocampus has been linked to cognitive deficits and increased risk of dementia. We utilized postmortem human hippocampal tissue from 26 subjects aged 18–88 years to investigate changes in expression of six genes representing different stages of neurogenesis across the healthy adult lifespan. Progressive and significant decreases in mRNA levels of the proliferation marker Ki67 (MKI67) and the immature neuronal marker doublecortin (DCX) were found in the healthy human hippocampus over the lifespan. In contrast, expression of genes for the stem cell marker glial...
Source: Aging Cell - August 1, 2017 Category: Cytology Authors: Kathryn J. Mathews, Katherine M. Allen, Danny Boerrigter, Helen Ball, Cynthia Shannon Weickert, Kay L. Double Tags: Short Take Source Type: research

The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore
Summary Excessive production of mitochondrial reactive oxygen species (mROS) is strongly associated with mitochondrial and cellular oxidative damage, aging, and degenerative diseases. However, mROS also induces pathways of protection of mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent studies show that the activation of the mitochondrial permeability transition pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is enhanced in aged animals and humans and in aging‐related degenerative diseases. mPTP opening initiates further production and release of mROS that dama...
Source: Aging Cell - July 31, 2017 Category: Cytology Authors: Hagai Rottenberg, Jan B. Hoek Tags: Review Source Type: research

Mitofusin 1 and optic atrophy 1 shift metabolism to mitochondrial respiration during aging
This study investigated whether changes in metabolism occur during aging of quiescent normal human fibroblasts (NHFs) and the mechanisms that regulate these changes. Bioenergetics measurements were taken in quiescent NHFs from younger (newborn, 3‐day, 5‐month, and 1‐year) and older (58‐, 61‐, 63‐, 68‐, and 70‐year) healthy donors as well as NHFs from the same individual at different ages (29, 36, and 46 years). Results show significant changes in cellular metabolism during aging of quiescent NHFs: Old NHFs exhibit a significant decrease in glycolytic flux and lactate levels, and increase in oxygen cons...
Source: Aging Cell - July 31, 2017 Category: Cytology Authors: Jyung Mean Son, Ehab H. Sarsour, Anurag Kakkerla Balaraju, Jenna Fussell, Amanda L. Kalen, Brett A. Wagner, Garry R. Buettner, Prabhat C. Goswami Tags: Original Article Source Type: research

Combined deficiency of the Cnr1 and Cnr2 receptors protects against age ‐related bone loss by osteoclast inhibition
Summary The endocannabinoid system plays a role in regulating bone mass and bone cell activity and inactivation of the type 1 (Cnr1) or type 2 (Cnr2) cannabinoid receptors influences peak bone mass and age‐related bone loss. As the Cnr1 and Cnr2 receptors have limited homology and are activated by different ligands, we have evaluated the effects of combined deficiency of Cnr1 and 2 receptors (Cnr1/2−/−) on bone development from birth to old age and studied ovariectomy induced bone loss in female mice. The Cnr1/2−/− mice had accelerated bone accrual at birth when compared with wild type littermates...
Source: Aging Cell - July 28, 2017 Category: Cytology Authors: Antonia Sophocleous, Silvia Marino, Dilruba Kabir, Stuart H. Ralston, Aymen I. Idris Tags: Original Article Source Type: research

Serpine 1 induces alveolar type II cell senescence through activating p53 ‐p21‐Rb pathway in fibrotic lung disease
This study reveals a novel function of PAI‐1 in regulation of cell cycle and suggests that elevation of PAI‐1 contributes importantly to ATII cell senescence in fibrotic lung diseases. (Source: Aging Cell)
Source: Aging Cell - July 19, 2017 Category: Cytology Authors: Chunsun Jiang, Gang Liu, Tracy Luckhardt, Veena Antony, Yong Zhou, A. Brent Carter, Victor J. Thannickal, Rui ‐Ming Liu Tags: Original Article Source Type: research

FOXO3 longevity interactome on chromosome 6
Summary FOXO3 has been implicated in longevity in multiple populations. By DNA sequencing in long‐lived individuals, we identified all single nucleotide polymorphisms (SNPs) in FOXO3 and showed 41 were associated with longevity. Thirteen of these had predicted alterations in transcription factor binding sites. Those SNPs appeared to be in physical contact, via RNA polymerase II binding chromatin looping, with sites in the FOXO3 promoter, and likely function together as a cis‐regulatory unit. The SNPs exhibited a high degree of LD in the Asian population, in which they define a specific longevity haplotype that is relat...
Source: Aging Cell - July 19, 2017 Category: Cytology Authors: Timothy A. Donlon, Brian J. Morris, Randi Chen, Kamal H. Masaki, Richard C. Allsopp, D. Craig Willcox, Ayako Elliott, Bradley J. Willcox Tags: Original Article Source Type: research

Nrf2 as a target for prevention of age ‐related and diabetic cataracts by against oxidative stress
Summary Cataract is one of the most important causes of blindness worldwide, with age‐related cataract being the most common one. Agents preventing cataract formation are urgently required. Substantial evidences point out aggravated oxidative stress as a vital factor for cataract formation. Nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2)/Kelch‐like erythroid‐cell‐derived protein with CNC homology (ECH)‐associated protein 1 (Keap1) system is considered as one of the main cellular defense mechanisms against oxidative stresses. This review discusses the role of Nrf2 pathway in the prevention of cataracts and ...
Source: Aging Cell - July 19, 2017 Category: Cytology Authors: Xiu ‐Fen Liu, Ji‐Long Hao, Tian Xie, Tayyab Hamid Malik, Cheng‐Bo Lu, Cong Liu, Chang Shu, Cheng‐Wei Lu, Dan‐Dan Zhou Tags: Review Source Type: research

Translation fidelity coevolves with longevity
Summary Whether errors in protein synthesis play a role in aging has been a subject of intense debate. It has been suggested that rare mistakes in protein synthesis in young organisms may result in errors in the protein synthesis machinery, eventually leading to an increasing cascade of errors as organisms age. Studies that followed generally failed to identify a dramatic increase in translation errors with aging. However, whether translation fidelity plays a role in aging remained an open question. To address this issue, we examined the relationship between translation fidelity and maximum lifespan across 17 rodent specie...
Source: Aging Cell - July 14, 2017 Category: Cytology Authors: Zhonghe Ke, Pramit Mallik, Adam B. Johnson, Facundo Luna, Eviatar Nevo, Zhengdong D. Zhang, Vadim N. Gladyshev, Andrei Seluanov, Vera Gorbunova Tags: Original Article Source Type: research

The emerging role of alternative splicing in senescence and aging
Summary Deregulation of precursor mRNA splicing is associated with many illnesses and has been linked to age‐related chronic diseases. Here we review recent progress documenting how defects in the machinery that performs intron removal and controls splice site selection contribute to cellular senescence and organismal aging. We discuss the functional association linking p53, IGF‐1, SIRT1, and ING‐1 splice variants with senescence and aging, and review a selection of splicing defects occurring in accelerated aging (progeria), vascular aging, and Alzheimer's disease. Overall, it is becoming increasingly clear that chan...
Source: Aging Cell - July 13, 2017 Category: Cytology Authors: Mathieu Desch ênes, Benoit Chabot Tags: Review Source Type: research

(Source: Aging Cell)
Source: Aging Cell - July 12, 2017 Category: Cytology Tags: Announcement Source Type: research

(Source: Aging Cell)
Source: Aging Cell - July 12, 2017 Category: Cytology Tags: Corrigendum Source Type: research

(Source: Aging Cell)
Source: Aging Cell - July 12, 2017 Category: Cytology Tags: Erratum Source Type: research

Issue Information
(Source: Aging Cell)
Source: Aging Cell - July 12, 2017 Category: Cytology Tags: Issue Information Source Type: research

Anti ‐aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application
Summary Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition...
Source: Aging Cell - July 5, 2017 Category: Cytology Authors: Pan Zhao, Bing ‐Dong Sui, Nu Liu, Ya‐Jie Lv, Chen‐Xi Zheng, Yong‐Bo Lu, Wen‐Tao Huang, Cui‐Hong Zhou, Ji Chen, Dan‐Lin Pang, Dong‐Dong Fei, Kun Xuan, Cheng‐Hu Hu, Yan Jin Tags: Original Article Source Type: research

Small RNAs induce the activation of the pro ‐inflammatory TLR7 signaling pathway in aged rat kidney
Summary We have recently reported that TLR‐related genes, including TLR7, are upregulated during aging. However, the role of TLR7 and its endogenous ligand in inflammation related to aging is not well defined. Here, we established that small RNAs trigger age‐related renal inflammation via TLR7 signaling pathway. We first investigated the expression changes of nine different TLRs in kidney of 6‐month‐old young rats and 20‐month‐old aged rats. The results revealed that the expression of TLR7 was the highest among nine TLRs in kidney of old rats compared to the young aged rats. Next, to assess the role of cellular...
Source: Aging Cell - June 30, 2017 Category: Cytology Authors: Eun Kyeong Lee, Ki Wung Chung, Ye Ra Kim, Sugyeong Ha, Sung Dae Kim, Dae Hyun Kim, Kyung Jin Jung, Bonggi Lee, Eunok Im, Byung Pal Yu, Hae Young Chung Tags: Original Article Source Type: research

The SKN ‐1/Nrf2 transcription factor can protect against oxidative stress and increase lifespan in C. elegans by distinct mechanisms
Summary In C. elegans, the skn‐1 gene encodes a transcription factor that resembles mammalian Nrf2 and activates a detoxification response. skn‐1 promotes resistance to oxidative stress (Oxr) and also increases lifespan, and it has been suggested that the former causes the latter, consistent with the theory that oxidative damage causes aging. Here, we report that effects of SKN‐1 on Oxr and longevity can be dissociated. We also establish that skn‐1 expression can be activated by the DAF‐16/FoxO transcription factor, another central regulator of growth, metabolism, and aging. Notably, skn‐1 is required for ...
Source: Aging Cell - June 14, 2017 Category: Cytology Authors: Jennifer M.A. Tullet, James W. Green, Catherine Au, Alexandre Benedetto, Maximillian A. Thompson, Emily Clark, Ann F. Gilliat, Adelaide Young, Kathrin Schmeisser, David Gems Tags: Short Take Source Type: research

Transcriptional coactivator with PDZ ‐binding motif is required to sustain testicular function on aging
Summary Transcriptional coactivator with PDZ‐binding motif (TAZ) directly interacts with transcription factors and regulates their transcriptional activity. Extensive functional studies have shown that TAZ plays critical regulatory roles in stem cell proliferation, differentiation, and survival and also modulates the development of organs such as the lung, kidney, heart, and bone. Despite the importance of TAZ in stem cell maintenance, TAZ function has not yet been evaluated in spermatogenic stem cells of the male reproductive system. Here, we investigated the expression and functions of TAZ in mouse testis. TAZ was expr...
Source: Aging Cell - June 14, 2017 Category: Cytology Authors: Mi Gyeong Jeong, Hyuna Song, Ji Hyun Shin, Hana Jeong, Hyo Kyeong Kim, Eun Sook Hwang Tags: Original Article Source Type: research

Reprogramming progeria fibroblasts re ‐establishes a normal epigenetic landscape
Summary Ideally, disease modeling using patient‐derived induced pluripotent stem cells (iPSCs) enables analysis of disease initiation and progression. This requires any pathological features of the patient cells used for reprogramming to be eliminated during iPSC generation. Hutchinson–Gilford progeria syndrome (HGPS) is a segmental premature aging disorder caused by the accumulation of the truncated form of Lamin A known as Progerin within the nuclear lamina. Cellular hallmarks of HGPS include nuclear blebbing, loss of peripheral heterochromatin, defective epigenetic inheritance, altered gene expression, and senes...
Source: Aging Cell - June 8, 2017 Category: Cytology Authors: Zhaoyi Chen, Wing Y. Chang, Alton Etheridge, Hilmar Strickfaden, Zhigang Jin, Gareth Palidwor, Ji ‐Hoon Cho, Kai Wang, Sarah Y. Kwon, Carole Doré, Angela Raymond, Akitsu Hotta, James Ellis, Rita A. Kandel, F. Jeffrey Dilworth, Theodore J. Perkins, Mich Tags: Original Article Source Type: research

Advances in Therapeutic Approaches to Extend Healthspan: a perspective from the 2nd Scripps Symposium on the Biology of Aging
Summary The 2nd Scripps Florida Symposium on The Biology of Aging entitled ‘Advances in Therapeutic Approaches to Extend Healthspan’ was held on January 22nd–25th, 2017 at The Scripps Research Institute in Jupiter, Florida. The meeting highlighted a variety of therapeutic approaches in animal models of aging that either are or soon will be in clinic trials. For example, drugs targeting senescent cells, metformin, rapalogs, NAD precursors, young plasma, mitochondrial‐targeted free radical scavengers, stem cells, and stem cell factors all have shown significant preclinical efficacy. This perspective, base...
Source: Aging Cell - June 6, 2017 Category: Cytology Authors: Paul D. Robbins, Laura J. Niedernhofer Tags: Commentary Source Type: research

Analysis of individual cells identifies cell ‐to‐cell variability following induction of cellular senescence
Summary Senescent cells play important roles in both physiological and pathological processes, including cancer and aging. In all cases, however, senescent cells comprise only a small fraction of tissues. Senescent phenotypes have been studied largely in relatively homogeneous populations of cultured cells. In vivo, senescent cells are generally identified by a small number of markers, but whether and how these markers vary among individual cells is unknown. We therefore utilized a combination of single‐cell isolation and a nanofluidic PCR platform to determine the contributions of individual cells to the overall ge...
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Christopher D. Wiley, James M. Flynn, Christapher Morrissey, Ronald Lebofsky, Joe Shuga, Xiao Dong, Marc A. Unger, Jan Vijg, Simon Melov, Judith Campisi Tags: Original Article Source Type: research

Cooperation between p21 and Akt is required for p53 ‐dependent cellular senescence
In this study, we have shown that both Akt and p21 are required to induce cellular senescence in response to p53 expression. In a p53‐induced senescence model, we found that Akt activation was essential for inducing a cellular senescence phenotype. Surprisingly, Akt inhibition did not abolish p53‐induced cell cycle arrest, but it suppressed the increase in intracellular reactive oxygen species (ROS) levels. The results of the cell cycle and morphological analysis suggest that p53 induced quiescence, not senescence, following Akt inhibition. Conversely, the inhibition of p21 induction abolished cell cycle arrest but did...
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Young Yeon Kim, Hye Jin Jee, Jee ‐Hyun Um, Young Mi Kim, Sun Sik Bae, Jeanho Yun Tags: Original Article Source Type: research

Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: role of Sirt1 ‐mediated autophagy regulation
In conclusion, our data indicate that Akt2 ablation protects against cardiac aging through restored Foxo1‐related autophagy and mitochondrial integrity. (Source: Aging Cell)
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Jun Ren, Lifang Yang, Li Zhu, Xihui Xu, Asli F. Ceylan, Wei Guo, Jian Yang, Yingmei Zhang Tags: Original Article Source Type: research

Caloric restriction impacts plasma microRNAs in rhesus monkeys
Summary Caloric restriction (CR) is one of the most robust interventions shown to delay aging in diverse species, including rhesus monkeys (Macaca mulatta). Identification of factors involved in CR brings a promise of translatability to human health and aging. Here, we show that CR induced a profound change in abundance of circulating microRNAs (miRNAs) linked to growth and insulin signaling pathway, suggesting that miRNAs are involved in CR's mechanisms of action in primates. Deep sequencing of plasma RNA extracts enriched for short species revealed a total of 243 unique species of miRNAs including 47 novel species. Appro...
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Augusto Schneider, Joseph M. Dhahbi, Hani Atamna, Josef P. Clark, Ricki J. Colman, Rozalyn M. Anderson Tags: Short Take Source Type: research

Epigenetic regulation by G9a/GLP complex ameliorates amyloid ‐beta 1‐42 induced deficits in long‐term plasticity and synaptic tagging/capture in hippocampal pyramidal neurons
Summary Altered epigenetic mechanisms are implicated in the cognitive decline associated with neurodegenerative diseases such as in Alzheimer's disease (AD). AD is the most prevalent form of dementia worldwide; amyloid plaques and neurofibrillary tangles are the histopathological hallmarks of AD. We have recently reported that the inhibition of G9a/GLP complex promotes long‐term potentiation (LTP) and its associative mechanisms such as synaptic tagging and capture (STC). However, the role of this complex in plasticity impairments remains elusive. Here, we investigated the involvement of G9a/GLP complex in alleviating the...
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Mahima Sharma, Tobias Dierkes, Sreedharan Sajikumar Tags: Original Article Source Type: research

The Piwi ‐piRNA pathway: road to immortality
Summary Despite its medical, social, and economic significance, understanding what primarily causes aging, that is, the mechanisms of the aging process, remains a fundamental and fascinating problem in biology. Accumulating evidence indicates that a small RNA‐based gene regulatory machinery, the Piwi‐piRNA pathway, represents a shared feature of nonaging (potentially immortal) biological systems, including the germline, somatic cancer stem cells, and certain ‘lower’ eukaryotic organisms like the planarian flatworm and freshwater hydra. The pathway primarily functions to repress the activity of mobile geneti...
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Ádám Sturm, András Perczel, Zoltán Ivics, Tibor Vellai Tags: Commentary Source Type: research

Methylation of the ribosomal RNA gene promoter is associated with aging and age ‐related decline
Summary The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpG dinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age‐related methylation status of the CpG island falling into the rDNA promoter in 472 blood samples from 20‐ to 105‐year‐old humans and in different tissues (blood, heart, liver, kidney, and testis) of 15 rats 3–96 weeks old. In humans, we did not find a consistently significant correlation between CpG site methylation and chronological age. Furthermore, the methylation l...
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Patrizia D'Aquila, Alberto Montesanto, Maurizio Mandal à, Sabrina Garasto, Vincenzo Mari, Andrea Corsonello, Dina Bellizzi, Giuseppe Passarino Tags: Original Article Source Type: research

Drug repurposing for aging research using model organisms
Summary Many increasingly prevalent diseases share a common risk factor: age. However, little is known about pharmaceutical interventions against aging, despite many genes and pathways shown to be important in the aging process and numerous studies demonstrating that genetic interventions can lead to a healthier aging phenotype. An important challenge is to assess the potential to repurpose existing drugs for initial testing on model organisms, where such experiments are possible. To this end, we present a new approach to rank drug‐like compounds with known mammalian targets according to their likelihood to modulate agin...
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Matthias Ziehm, Satwant Kaur, Dobril K. Ivanov, Pedro J. Ballester, David Marcus, Linda Partridge, Janet M. Thornton Tags: Original Article Source Type: research

TORC1 ‐mediated sensing of chaperone activity alters glucose metabolism and extends lifespan
Summary Protein quality control mechanisms, required for normal cellular functioning, encompass multiple functions related to protein production and maintenance. However, the existence of communication between proteostasis and metabolic networks and its underlying mechanisms remain elusive. Here, we report that enhanced chaperone activity and consequent improved proteostasis are sensed by TORC1 via the activity of Hsp82. Chaperone enrichment decreases the level of Hsp82, which deactivates TORC1 and leads to activation of Snf1/AMPK, regardless of glucose availability. This mechanism culminates in the extension of yeast repl...
Source: Aging Cell - June 1, 2017 Category: Cytology Authors: Matea Peri ć, Anita Lovrić, Ana Šarić, Marina Musa, Peter Bou Dib, Marina Rudan, Andrea Nikolić, Sandra Sobočanec, Ana‐Matea Mikecin, Sven Dennerlein, Ira Milošević, Kristian Vlahoviček, Nuno Raimundo, Anita Kriško Tags: Original Article Source Type: research