Search Our Scientific Publications & Authors

Aging Cell 2019 Apr 22:e12961. Epub 2019 Apr 22.

Department of Neurology, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Cav1.2 is the pore-forming subunit of L-type voltage-gated calcium channel (LTCC) that plays an important role in calcium overload and cell death in Alzheimer's disease. LTCC activity can be regulated by estrogen, a sex steroid hormone that is neuroprotective. Read More

Aging Cell 2019 Apr 15:e12958. Epub 2019 Apr 15.

Achucarro Basque Center for Neuroscience, Leioa, Spain.

Adult neurogenesis persists in the hippocampus of most mammal species during postnatal and adult life, including humans, although it declines markedly with age. The mechanisms driving the age-dependent decline of hippocampal neurogenesis are yet not fully understood. The progressive loss of neural stem cells (NSCs) is a main factor, but the true neurogenic output depends initially on the actual number of activated NSCs in each given time point. Read More

Aging Cell 2019 Apr 11:e12922. Epub 2019 Apr 11.

School of Medicine, Life and Health Sciences Research Institute (ICVS), University of Minho, Braga, Portugal.

α-Synuclein (aSyn) toxicity is associated with cell cycle alterations, activation of DNA damage responses (DDR), and deregulation of autophagy. However, the relationships between these phenomena remain largely unknown. Here, we demonstrate that in a yeast model of aSyn toxicity and aging, aSyn expression induces Ras2-dependent growth signaling, cell cycle re-entry, DDR activation, autophagy, and autophagic degradation of ribonucleotide reductase 1 (Rnr1), a protein required for the activity of ribonucleotide reductase and dNTP synthesis. Read More

Aging Cell 2019 Apr 9:e12952. Epub 2019 Apr 9.

Department of Embryology, Carnegie Institution for Science, Baltimore, Maryland.

Cellular architectural proteins often participate in organ development and maintenance. Although functional decay of some of these proteins during aging is known, the cell-type-specific developmental role and the cause and consequence of their subsequent decay remain to be established especially in mammals. By studying lamins, the nuclear structural proteins, we demonstrate that lamin-B1 functions specifically in the thymic epithelial cells (TECs) for proper thymus organogenesis. Read More

Aging Cell 2019 Apr 5:e12954. Epub 2019 Apr 5.

DAHFMO-Unit of Histology and Medical Embryology, Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.

The decline in skeletal muscle mass and strength occurring in aging, referred as sarcopenia, is the result of many factors including an imbalance between protein synthesis and degradation, changes in metabolic/hormonal status, and in circulating levels of inflammatory mediators. Thus, factors that increase muscle mass and promote anabolic pathways might be of therapeutic benefit to counteract sarcopenia. Among these, the insulin-like growth factor-1 (IGF-1) has been implicated in many anabolic pathways in skeletal muscle. Read More

Aging Cell 2019 Apr 3:e12940. Epub 2019 Apr 3.

Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.

Dysregulation of long noncoding RNAs (lncRNAs) is associated with abnormal development and pathophysiology in the brain. Increasing evidence has indicated that ischemic stroke is becoming the most common cerebral disease in aging populations. The treatment of ischemic stroke is challenging, due in part to ischemia and reperfusion (I/R) injury. Read More

Aging Cell 2019 Apr 2:e12934. Epub 2019 Apr 2.

Division of Orthopaedic Research, Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.

Age-related tendon degeneration (tendinosis) is characterized by a phenotypic change in which tenocytes display characteristics of fibrochondrocytes and mineralized fibrochondrocytes. As tendon degeneration has been noted in vivo in areas of decreased tendon vascularity, we hypothesized that hypoxia is responsible for the development of the tendinosis phenotype, and that these effects are more pronounced in aged tenocytes. Hypoxic (1% O ) culture of aged, tendinotic, and young human tenocytes resulted in a mineralized fibrochondrocyte phenotype in aged tenocytes, and a fibrochondrocyte phenotype in young and tendinotic tenocytes. Read More

Aging Cell 2019 Apr 1:e12944. Epub 2019 Apr 1.

Department of Cellular and Integrative Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Calorie restriction (CR), which lengthens lifespan in many species, is associated with moderate hyperadrenocorticism and attenuated inflammation. Given the anti-inflammatory action of glucocorticoids, we tested the hypothesis that the hyperadrenocorticism of CR contributes to its attenuated inflammatory response. We used a corticotropin-releasing-hormone knockout (CRHKO) mouse, which is glucocorticoid insufficient. Read More

Aging Cell 2019 Mar 29:e12943. Epub 2019 Mar 29.

Division of Thoracic Surgery, Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, California.

Aging leads to skeletal muscle atrophy (i.e., sarcopenia), and muscle fiber loss is a critical component of this process. Read More

Aging Cell 2019 Mar 28:e12948. Epub 2019 Mar 28.

Department of Basic Sciences of Health, Area of Biochemistry and Molecular Biology, Universidad Rey Juan Carlos, Alcorcon-Madrid, Spain.

Age-related increased adiposity is an important contributory factor in the development of insulin resistance (IR) and is associated with metabolic defects. Caloric restriction (CR) is known to induce weight loss and to decrease adiposity while preventing metabolic risk factors. Here, we show that moderate 20% CR delays early deleterious effects of aging on white and brown adipose tissue (WAT and BAT, respectively) function and improves peripheral IR. Read More

Aging Cell 2019 Mar 28:e12945. Epub 2019 Mar 28.

Cardiovascular Research Centre, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK.

Cardiovascular disease is the leading cause of death in individuals over 60 years old. Aging is associated with an increased prevalence of coronary artery disease and a poorer prognosis following acute myocardial infarction (MI). With age, senescent cells accumulate in tissues, including the heart, and contribute to age-related pathologies. Read More

Aging Cell 2019 Mar 28:e12949. Epub 2019 Mar 28.

National Institute on Aging, National Institutes of Health, Baltimore, Maryland.

In mutant mice, reduced levels of Klotho promoted high levels of active vitamin D in the serum. Genetic or dietary manipulations that diminished active vitamin D alleviated aging-related phenotypes caused by Klotho down-regulation. The hypomorphic Klotho [kl/kl] allele that decreases Klotho expression in C3H, BALB/c, 129, and C57BL/6 genetic backgrounds substantially increases 1,25(OH)2D3 levels in the sera of susceptible C3H, BALB/c, and 129, but not C57BL/6 mice. Read More

Aging Cell 2019 Mar 27:e12935. Epub 2019 Mar 27.

Department of Biology, Glenn Labs for the Science of Aging, and Koch Institute, MIT, Cambridge, Massachusetts.

The tissue decline due to aging is associated with the deterioration of adult stem cell function. Here we show the number and proliferative activity of intestinal stem cells (ISCs) but not Paneth cells decline during aging, as does ISC function assessed ex vivo. Levels of SIRT1 and activity of mTORC1 also decline with aging. Read More

Aging Cell 2019 Mar 27:e12946. Epub 2019 Mar 27.

Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK.

Interleukin-1 alpha (IL-1α) is a powerful cytokine that modulates immunity, and requires canonical cleavage by calpain for full activity. Mature IL-1α is produced after inflammasome activation and during cell senescence, but the protease cleaving IL-1α in these contexts is unknown. We show IL-1α is activated by caspase-5 or caspase-11 cleavage at a conserved site. Read More

Aging Cell 2019 Mar 27:e12953. Epub 2019 Mar 27.

Department of Pharmacology, Barshop Institute for Longevity and Aging Studies, Geriatric Research, Education and Clinical Center and Research Service, South Texas Veterans Health Care System, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.

Diets low in methionine extend lifespan of rodents, though through unknown mechanisms. Glycine can mitigate methionine toxicity, and a small prior study has suggested that supplemental glycine could extend lifespan of Fischer 344 rats. We therefore evaluated the effects of an 8% glycine diet on lifespan and pathology of genetically heterogeneous mice in the context of the Interventions Testing Program. Read More

Aging Cell 2019 Mar 25:e12955. Epub 2019 Mar 25.

State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.

Advanced maternal age has been reported to impair oocyte quality; however, the underlying mechanisms remain to be explored. In the present study, we identified the lowered NAD content and decreased expression of NMNAT2 protein in oocytes from old mice. Specific depletion of NMNAT2 in mouse oocytes disturbs the meiotic apparatus assembly and metabolic activity. Read More

Aging Cell 2019 Mar 25:e12947. Epub 2019 Mar 25.

Department of Molecular Biology, Cell Biology and Biochemistry, and Center on the Biology of Aging, Brown University, Providence, Rhode Island.

Mice that express reduced levels of the c-Myc gene (Myc heterozygotes) are long-lived. Myc hypomorphic mice display reduced rates of protein translation and decreased activity of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). Given the prominent effect of mTOR on aging, lower mTORC1 activity could contribute to the exceptional longevity and enhanced healthspan of Myc animals. Read More

Aging Cell 2019 Mar 24:e12951. Epub 2019 Mar 24.

State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.

We tested the hypothesis that 1,25-dihydroxyvitamin D [1α,25(OH) D ] has antiaging effects via upregulating nuclear factor (erythroid-derived 2)-like 2 (Nrf2), reducing reactive oxygen species (ROS), decreasing DNA damage, reducing p16/Rb and p53/p21 signaling, increasing cell proliferation, and reducing cellular senescence and the senescence-associated secretory phenotype (SASP). We demonstrated that 1,25(OH) D -deficient [1α(OH)ase ] mice survived on average for only 3 months. Increased tissue oxidative stress and DNA damage, downregulated Bmi1 and upregulated p16, p53 and p21 expression levels, reduced cell proliferation, and induced cell senescence and the senescence-associated secretory phenotype (SASP) were observed. Read More

Aging Cell 2019 Mar 21:e12927. Epub 2019 Mar 21.

Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.

Rationale: Age-related changes in the intervertebral discs are the predominant contributors to back pain, a common physical and functional impairment experienced by older persons. Cellular senescence, a process wherein cells undergo growth arrest and chronically secrete numerous inflammatory molecules and proteases, has been reported to cause decline in the health and function of multiple tissues with age. Although senescent cells have been reported to increase in intervertebral degeneration (IDD), it is not known whether they are causative in age-related IDD. Read More

Aging Cell 2019 Mar 18:e12932. Epub 2019 Mar 18.

Department of Molecular Neuropathology, Centro de Biología Molecular Severo Ochoa, CSIC/UAM, Madrid, Spain.

In the brain, insulin plays an important role in cognitive processes. During aging, these faculties decline, as does insulin signaling. The mechanism behind this last phenomenon is unclear. Read More

Aging Cell 2019 Mar 18:e12936. Epub 2019 Mar 18.

Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.

Vascular stiffness is a major cause of cardiovascular disease during normal aging and in Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder caused by ubiquitous progerin expression. This mutant form of lamin A causes premature aging associated with cardiovascular alterations that lead to death at an average age of 14.6 years. Read More

Aging Cell 2019 Mar 13:e12928. Epub 2019 Mar 13.

Temasek Life Sciences Laboratory, National University of Singapore, Singapore.

Intron retention (IR) by alternative splicing is a conserved regulatory mechanism that can affect gene expression and protein function during adult development and age-onset diseases. However, it remains unclear whether IR undergoes spatial or temporal changes during different stages of aging or neurodegeneration like Alzheimer's disease (AD). By profiling the transcriptome of Drosophila head cells at different ages, we observed a significant increase in IR events for many genes during aging. Read More

Aging Cell 2019 Apr;18(2):e12917

Aging Cell 2019 Apr;18(2):e12942

Aging Cell 2019 Mar 10:e12931. Epub 2019 Mar 10.

School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, Kings College London, London, UK.

Aging leads to increased cellular senescence and is associated with decreased potency of tissue-specific stem/progenitor cells. Here, we have done an extensive analysis of cardiac progenitor cells (CPCs) isolated from human subjects with cardiovascular disease, aged 32-86 years. In aged subjects (>70 years old), over half of CPCs are senescent (p16 , SA-β-gal, DNA damage γH2AX, telomere length, senescence-associated secretory phenotype [SASP]), unable to replicate, differentiate, regenerate or restore cardiac function following transplantation into the infarcted heart. Read More

Aging Cell 2019 Mar 8:e12938. Epub 2019 Mar 8.

Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado.

Recent reports by Martincorena et al and Yokoyama et al reveal unanticipated dynamics of somatic evolution in the esophageal epithelium, with clonal expansions apparently driven by mutations in Notch1 dominating the epithelium even in middle-aged individuals, far outpacing the prevalence of these mutations in esophageal cancers. We propose a model whereby the promotion of clonal expansions by mutations such as in Notch1 can limit more malignant somatic evolutionary trajectories until old ages. Read More

Aging Cell 2019 Mar 7:e12918. Epub 2019 Mar 7.

Institute of Aging Research, Guangdong Medical University, Dongguan, China.

Aging is a multifactorial process characterized by the progressive deterioration of physiological functions. Among the multiple molecular mechanisms, microRNAs (miRNAs) have increasingly been implicated in the regulation of Aging process. However, the contribution of miRNAs to physiological Aging and the underlying mechanisms remain elusive. Read More

Aging Cell 2019 Mar 7:e12939. Epub 2019 Mar 7.

Departments of Chemical & Biomedical and Medical Engineering, Global Center for Hearing & Speech Research, University of South Florida, Tampa, Florida.

Estradiol (E) is a multitasking hormone that plays a prominent role in the reproductive system, and also contributes to physiological and growth mechanisms throughout the body. Frisina and colleagues have previously demonstrated the beneficial effects of this hormone, with E-treated subjects maintaining low auditory brainstem response (ABR) thresholds relative to control subjects (Proceedings of the National Academy of Sciences of the United States of America, 2006;103:14246; Hearing Research, 2009;252:29). In the present study, we evaluated the functionality of the peripheral and central auditory systems in female CBA/CaJ middle-aged mice during and after long-term hormone replacement therapy (HRT) via electrophysiological and molecular techniques. Read More

Aging Cell 2019 Mar 5:e12941. Epub 2019 Mar 5.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.

Cardiolipin (CL) is a mitochondrial signature phospholipid that is required for membrane structure, respiration, dynamics, and mitophagy. Oxidative damage of CL by reactive oxygen species is implicated in the pathogenesis of Parkinson's disease (PD), but the underlying cause remains elusive. This work investigated the role of ALCAT1, an acyltransferase that catalyzes pathological remodeling of CL in various aging-related diseases, in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine (MPTP). Read More

Aging Cell 2019 Mar 4:e12926. Epub 2019 Mar 4.

Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Biological aging dynamically alters normal immune and cardiac function, favoring the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased instances of cardiac distress. Cardiac failure is the primary reason for hospitalization of the elderly (65+ years). The elderly are also increasingly susceptible to developing chronic bacterial infections due to aging associated immune abnormalities. Read More

Aging Cell 2019 Mar 3:e12933. Epub 2019 Mar 3.

San Raffaele Telethon Institute for Gene Therapy, Milan, Italy.

Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) niche and serve as a reservoir for mature blood cells throughout life. Aging in the BM is characterized by low-grade chronic inflammation that could contribute to the reduced functionality of aged HSPC. Mesenchymal stromal cells (MSC) in the BM support HSPC self-renewal. Read More

Aging Cell 2019 Mar 1:e12874. Epub 2019 Mar 1.

Department of Physiology and Institute for Diabetes, Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

The prevalence of obesity increases with age in humans and in rodents. Age-related obesity is characterized by leptin resistance and associated with heightened risk of metabolic disorders. However, the effect of leptin resistance per se has been difficult to disentangle from other effects of aging. Read More

Aging Cell 2019 Mar 1:e12887. Epub 2019 Mar 1.

Inserm U1144, Paris, France.

Brain lesions in Alzheimer's disease (AD) include amyloid plaques made of Aβ peptides and neurofibrillary tangles composed of hyperphosphorylated tau protein with synaptic and neuronal loss and neuroinflammation. Aβ oligomers can trigger tau phosphorylation and neuronal alterations through activation of neuronal kinases leading to progressive cognitive decline. PKR is a ubiquitous pro-apoptotic serine/threonine kinase, and levels of activated PKR are increased in AD brains and AD CSF. Read More

Aging Cell 2019 Feb 28:e12930. Epub 2019 Feb 28.

Laboratory of Molecular Pathology, Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.

To survive and reproduce, living organisms must evolve numerous mechanisms to re-adjust their physiology when encountering adverse conditions that subject them to severe stress. We found that short-term starvation (STS) stress in young adult male Caenorhabditis elegans can significantly improve their vitality (relative to nonstressed males) when they are aged. In addition, we found that stress-treated aged males maintained reproductive activity equivalent to young males, whereas nonstressed aged males quickly lost reproductive ability. Read More

Aging Cell 2019 Feb 27:e12937. Epub 2019 Feb 27.

Department of Pathology and Laboratory Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania.

Astrocytes participate in numerous aspects of central nervous system (CNS) physiology ranging from ion balance to metabolism, and disruption of their physiological roles can therefore be a contributor to CNS dysfunction and pathology. Cellular senescence, one of the mechanisms of aging, has been proposed as a central component of the age dependency of neurodegenerative disorders. Cumulative evidence supports an integral role of astrocytes in the initiation and progression of neurodegenerative disease and cognitive decline with aging. Read More

Aging Cell 2019 Feb 27:e12849. Epub 2019 Feb 27.

The Buck Institute for Research on Aging, Novato, California.

Aging is associated with a progressive loss of tissue and metabolic homeostasis. This loss can be delayed by single-gene perturbations, increasing lifespan. How such perturbations affect metabolic and proteostatic networks to extend lifespan remains unclear. Read More

Aging Cell 2019 Feb 27:e12919. Epub 2019 Feb 27.

Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, California.

Diabetes mellitus (DM) is one of the most devastating diseases that currently affects the aging population. Recent evidence indicates that DM is a risk factor for many brain disorders, due to its direct effects on cognition. New findings have shown that the microtubule-associated protein tau is pathologically processed in DM; however, it remains unknown whether pathological tau modifications play a central role in the cognitive deficits associated with DM. Read More

Aging Cell 2019 Feb 27:e12929. Epub 2019 Feb 27.

Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Tauopathies are a class of neurodegenerative diseases that are characterized by pathological aggregation of tau protein, which is accompanied by synaptic disorders. However, the role of tau in endocytosis, a fundamental process in synaptic transmission, remains elusive. Here, we report that forced expression of human tau (hTau) in mouse cortical neurons impairs endocytosis by decreasing the level of the GTPase dynamin 1 via disruption of the miR-132-MeCP2 pathway; this process can also be detected in the brains of Alzheimer's patients and hTau mice. Read More

Aging Cell 2019 Feb 23:e12905. Epub 2019 Feb 23.

Barshop Institute for Longevity and Aging Studies, UT Health San Antonio, San Antonio, Texas.

The female survival advantage is a robust characteristic of human longevity. However, underlying mechanisms are not understood, and rodent models exhibiting a female advantage are lacking. Here, we report that the genetically heterogeneous (UM-HET3) mice used by the National Institute on Aging Interventions Testing Program (ITP) are such a model. Read More

Aging Cell 2019 Apr 22;18(2):e12850. Epub 2019 Feb 22.

U995 - Lille Inflammation Research International Center, INSERM, CHU Lille, University of Lille, Lille, France.

Pro-aging effects of endogenous advanced glycation end-products (AGEs) have been reported, and there is increasing interest in the pro-inflammatory and -fibrotic effects of their binding to RAGE (the main AGE receptor). The role of dietary AGEs in aging remains ill-defined, but the predominantly renal accumulation of dietary carboxymethyllysine (CML) suggests the kidneys may be particularly affected. We studied the impact of RAGE invalidation and a CML-enriched diet on renal aging. Read More

Aging Cell 2019 Feb 21:e12924. Epub 2019 Feb 21.

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland.

Mitochondrial dysfunction is implicated in most neurodegenerative diseases, including Alzheimer's disease (AD). We here combined experimental and computational approaches to investigate mitochondrial health and bioenergetic function in neurons from a double transgenic animal model of AD (PS2APP/B6.152H). Read More

Aging Cell 2019 Feb 21:e12907. Epub 2019 Feb 21.

Epidemiology and Biostatistics, Department of Public Health, University of Southern Denmark, Odense, Denmark.

The Y chromosome, a sex chromosome that only exists in males, has been ignored in traditional epigenetic association studies for multiple reasons. However, sex differences in aging-related phenotypes and mortality could suggest a critical role of the sex chromosomes in the aging process. We obtained blood-based DNA methylation data on the Y chromosome for 624 men from four cohorts and performed a chromosome-wide epigenetic association analysis to detect Y-linked CpGs differentially methylated over age and cross-validated the significant CpGs in the four cohorts. Read More

Aging Cell 2019 Feb 20:e12921. Epub 2019 Feb 20.

Department of Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.

Calorie restriction is the only physiological intervention that extends lifespan throughout all kingdoms of life. In the budding yeast Saccharomyces cerevisiae, cytosolic pH (pH ) controls growth and responds to nutrient availability, decreasing upon glucose depletion. We investigated the interactions between glucose availability, pH and the central nutrient signalling cAMP-Protein Kinase A (PKA) pathway. Read More

Aging Cell 2019 Feb 20:e12914. Epub 2019 Feb 20.

Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.

We previously reported that the canonical innate immune receptor toll-like receptor 4 (TLR4) is critical in maintaining lung integrity. However, the molecular mechanisms via which TLR4 mediates its effect remained unclear. In the present study, we identified distinct contributions of lung endothelial cells (Ec) and epithelial cells TLR4 to pulmonary homeostasis using genetic-specific, lung- and cell-targeted in vivo methods. Read More

Aging Cell 2019 Feb 17:e12913. Epub 2019 Feb 17.

Department of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.

Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin-angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers. Read More

Aging Cell 2019 Feb 17:e12923. Epub 2019 Feb 17.

Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas.

Both an increase in osteoclast and a decrease in osteoblast numbers contribute to skeletal aging. Markers of cellular senescence, including expression of the cyclin inhibitor p16, increase with aging in several bone cell populations. The elimination of p16-expressing cells in old mice, using the INK-ATTAC transgene, increases bone mass indicating that senescent cells contribute to skeletal aging. Read More

Aging Cell 2019 Feb 17:e12896. Epub 2019 Feb 17.

National Institute of Biological Sciences, Beijing, China.

The roles and regulatory mechanisms of transcriptome changes during aging are unclear. It has been proposed that the transcriptome suffers decay during aging owing to age-associated down-regulation of transcription factors. In this study, we characterized the role of a transcription factor DAF-16, which is a highly conserved lifespan regulator, in the normal aging process of Caenorhabditis elegans. Read More

Aging Cell 2019 Feb 17:e12906. Epub 2019 Feb 17.

Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, South Korea.

PDZ domain-containing proteins (PDZ proteins) act as scaffolds for protein-protein interactions and are crucial for a variety of signal transduction processes. However, the role of PDZ proteins in organismal lifespan and aging remains poorly understood. Here, we demonstrate that KIN-4, a PDZ domain-containing microtubule-associated serine-threonine (MAST) protein kinase, is a key longevity factor acting through binding PTEN phosphatase in Caenorhabditis elegans. Read More

Aging Cell 2019 Feb 15:e12903. Epub 2019 Feb 15.

Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.

Down syndrome (DS) has been proposed by George Martin as a segmental progeroid syndrome since 1978. In fact, DS persons suffer from several age-associated disorders much earlier than euploid persons. Furthermore, a series of recent studies have found that DS persons display elevated levels of age biomarkers, thus supporting the notion that DS is a progeroid trait. Read More