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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

Aging Cell 2019 Feb 15:e12916. Epub 2019 Feb 15.

Department of Biological Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Naked mole-rats (NMRs) are mouse-sized mammals that exhibit an exceptionally long lifespan (>30 vs. <4 years for mice), and resist aging-related pathologies such as cardiovascular and pulmonary diseases, cancer, and neurodegeneration. However, the mechanisms underlying this exceptional longevity and disease resistance remain poorly understood. Read More

Aging Cell 2019 Feb 14:e12912. Epub 2019 Feb 14.

Department of Pathology, Case Western Reserve University, Cleveland, Ohio.

Abnormal mitochondrial dynamics contributes to mitochondrial dysfunction in Alzheimer's disease (AD), yet the underlying mechanism remains elusive. In the current study, we reported that DLP1, the key mitochondrial fission GTPase, is a substrate of calpain which produced specific N-terminal DLP1 cleavage fragments. In addition, various AD-related insults such as exposure to glutamate, soluble amyloid-β oligomers, or reagents inducing tau hyperphosphorylation (i. Read More

Aging Cell 2019 Feb 11:e12925. Epub 2019 Feb 11.

Groupe de recherche PRIMUS, Department of Family Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada.

Two major goals in the current biology of aging are to identify general mechanisms underlying the aging process and to explain species differences in aging. Recent research in humans suggests that one important driver of aging is dysregulation, the progressive loss of homeostasis in complex biological networks. Yet, there is a lack of comparative data for this hypothesis, and we do not know whether dysregulation is widely associated with aging or how well signals of homeostasis are conserved. Read More

Aging Cell 2019 Feb 11:e12888. Epub 2019 Feb 11.

Department of Brain and Cognitive Sciences, Ewha Womans University, Seoul, Korea.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by Aβ-induced pathology and progressive cognitive decline. The incidence of AD is growing globally, yet a prompt and effective remedy is not available. Aging is the greatest risk factor for AD. Read More

Aging Cell 2019 Feb 10:e12920. Epub 2019 Feb 10.

Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan.

Pharmacological treatments can extend mouse lifespan, but lifespan effects often differ between sexes. 17-α estradiol (17aE2), a less feminizing structural isomer of 17-β estradiol, produces lifespan extension only in male mice, suggesting a sexually dimorphic mechanism of lifespan regulation. We tested whether these anti-aging effects extend to anatomical and functional aging-important in late-life health-and whether gonadally derived hormones control aging responses to 17aE2 in either sex. Read More

Aging Cell 2019 Feb 8:e12853. Epub 2019 Feb 8.

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

Caenorhabditis elegans is an exceptionally valuable model for aging research because of many advantages, including its genetic tractability, short lifespan, and clear age-dependent physiological changes. Aged C. elegans display a decline in their anatomical and functional features, including tissue integrity, motility, learning and memory, and immunity. Read More

Aging Cell 2019 Feb 4:e12915. Epub 2019 Feb 4.

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

The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Read More

Aging Cell 2019 Feb 2:e12897. Epub 2019 Feb 2.

Division of Hematology/Oncology, Department of Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio.

The age of tissues and cells can be accurately estimated by DNA methylation analysis. The multitissue DNA methylation (DNAm) age predictor combines the DNAm levels of 353 CpG dinucleotides to arrive at an age estimate referred to as DNAm age. Recent studies based on short-term observations showed that the DNAm age of reconstituted blood following allogeneic hematopoietic stem cell transplantation (HSCT) reflects the age of the donor. Read More

Aging Cell 2019 Feb 1:e12911. Epub 2019 Feb 1.

European Research Institute for the Biology of Ageing, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Cellular senescence is a state of permanent cell cycle arrest activated in response to damaging stimuli. Many hallmarks associated with senescent cells are measured by quantitative real-time PCR (qPCR). As the selection of stable reference genes for interpretation of qPCR data is often overlooked, we performed a systematic review to understand normalization strategies entailed in experiments involving senescent cells. Read More

Aging Cell 2019 Feb 1:e12902. Epub 2019 Feb 1.

Department of Pathophysiology, Key Lab of Neurological Disorder of Education Ministry, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Impairments of dendritic trees and spines have been found in many neurodegenerative diseases, including Alzheimer's disease (AD), in which the deficits of melatonin signal pathway were reported. Melatonin receptor 2 (MT2) is widely expressed in the hippocampus and mediates the biological functions of melatonin. It is known that melatonin application is protective to dendritic abnormalities in AD. Read More

Aging Cell 2019 Jan 31:e12909. Epub 2019 Jan 31.

Department of Biotechnology, College of Life Science, CHA University, Pocheon-si, Korea.

Senescence in stem cells, which occurs as a consequence of chronic responses to the environment, defines the capacity of stem cells for proliferation and differentiation as well as their potential for tissue regeneration and homeostasis maintenance. Although stem cells reside under low oxygen pressure and the availability of oxygen is known to be a crucial determinant in their fate, the key modulators in stem cell aging and the underlying mechanism have yet to be unraveled. Human placenta-derived mesenchymal stem cells (hpMSCs) were cultured under hypoxia (3% O ) or normoxia (21% O ) to investigate the key factors that regulate stem cell senescence under hypoxic conditions. Read More

Aging Cell 2019 Jan 31:e12901. Epub 2019 Jan 31.

Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts.

Systemic inflammation is central to aging-related conditions. However, the intrinsic factors that induce inflammation are not well understood. We previously identified a cell-autonomous pathway through which damaged nuclear DNA is trafficked to the cytosol where it activates innate cytosolic DNA sensors that trigger inflammation. Read More

Aging Cell 2019 Jan 27:e12898. Epub 2019 Jan 27.

Department of Pathology, University of Michigan, Ann Arbor, Michigan.

To follow-up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log-rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. Read More

Aging Cell 2019 Jan 24:e12894. Epub 2019 Jan 24.

Faculté de Médecine, Laboratoire de Recherche en Physiologie et Physiopathologie, LRPP, Pôle Technologie Santé, Université Saint Joseph, Beyrouth, Liban.

With the onset of advanced age, cardiac-associated pathologies have increased in prevalence. The hallmarks of cardiac aging include cardiomyocyte senescence, fibroblast proliferation, inflammation, and hypertrophy. The imbalance between levels of reactive oxygen species (ROS) and antioxidant enzymes is greatly enhanced in aging cells, promoting cardiac remodeling. Read More

Aging Cell 2019 Jan 22:e12881. Epub 2019 Jan 22.

Key Laboratory of Regenerative Medicine, Ministry of Education, Jinan University, Guangzhou, China.

The mechanism of age-related decline in the angiogenic potential of the myocardium is not yet fully understood. Our previous report revealed that the aging of cardiac microvascular endothelial cells (CMECs) led to changes in their expression of receptor Trk isoforms: among the three isoforms (TrkB-FL, TrkB-T1 and TrkB-T2), only the truncated TrkB-T1 isoform continued to be expressed in aged CMECs, which led to decreased migration of CMECs in aging hearts. Thus far, how BDNF induces signalling through the truncated TrkB-T1 isoform in aged CMECs remains unclear. Read More

Aging Cell 2019 Jan 15:e12891. Epub 2019 Jan 15.

Department of Life Sciences, The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Protein homeostasis is remodeled early in Caenorhabditis elegans adulthood, resulting in a sharp decline in folding capacity and reduced ability to cope with chronic and acute stress. Endocrine signals from the reproductive system can ameliorate this proteostatic collapse and reshape the quality control network. Given that environmental conditions, such as food availability, impact reproductive success, we asked whether conditions of dietary restriction (DR) can also reverse the decline in quality control function at the transition to adulthood, and if so, whether gonadal signaling and dietary signaling remodel the quality control network in a similar or different manner. Read More

Aging Cell 2019 Jan 15:e12883. Epub 2019 Jan 15.

Department of Endocrinology, Wuhan General Hospital of Chinese People's Liberation Army, Wuhan, China.

Alogliptin is a commonly prescribed drug treating patients with type 2 diabetes. Here, we show that long-term intervention with alogliptin (0.03% w/w in diet) improves survival and health of mice on a high-fat diet. Read More

Aging Cell 2019 Jan 14:e12884. Epub 2019 Jan 14.

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

Microtubule (MT) regulation is involved in both neuronal function and the maintenance of neuronal structure, and MT dysregulation appears to be a general downstream indicator and effector of age-related neurodegeneration. But the role of MTs in natural aging is largely unknown. Here, we demonstrate a role of MT regulators in regulating longevity. Read More

Aging Cell 2019 Jan 13:e12892. Epub 2019 Jan 13.

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

We analyzed the small RNA transcriptome from 5-month-old, 24-month-old, and 36-month-old mouse liver and found 56 miRNAs that changed their expression profile with age. Among these is a cluster of 18 miRNAs that are upregulated between 50- and 1,000-fold at 24 and 36 months of age. This cluster is located in a 60-kb region of the X-chromosome that is devoid of other coding sequences and is part of a lamin-associated domain. Read More

Aging Cell 2019 Jan 11:e12893. Epub 2019 Jan 11.

Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.

The elderly exhibit increased mortality to influenza viral infection for unclear reasons. Mice are frequently used to model how aging impacts disease. Several studies have shown that aged mice exhibit an increased mortality to influenza virus, but two recent studies demonstrated the opposite. Read More

Aging Cell 2019 Jan 8:e12900. Epub 2019 Jan 8.

School of Basic Medicine, Shandong University, Jinan, Shandong Province, China.

The mammalian Sirt1 deacetylase is generally thought to be a nuclear protein, but some pilot studies have suggested that Sirt1 may also be involved in orchestrating nucleolar functions. Here, we show that nucleolar stress response is a ubiquitous cellular reaction that can be induced by different types of stress conditions, and Sirt1 is an endogenous suppressor of nucleolar stress response. Using stable isotope labeling by amino acids in cell culture approach, we have identified a physical interaction of between Sirt1 and the nucleolar protein nucleophosmin, and this protein-protein interaction appears to be necessary for Sirt1 inhibition on nucleolar stress, whereas the deacetylase activity of Sirt1 is not strictly required. Read More

Aging Cell 2019 Jan 6:e12904. Epub 2019 Jan 6.

Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea.

Although it is known that the expression and activity of sirtuin 1 (Sirt1) decrease in the aged kidney, the role of interaction between Sirt1 and hypoxia-inducible factor (HIF)-1α is largely unknown. In this study, we investigated whether HIF-1α could be a deacetylation target of Sirt1 and the effect of their interaction on age-associated renal injury. Five-week-old (young) and 24-month-old (old) C57Bl/6J mice were assessed for their age-associated changes. Read More

Aging Cell 2019 Jan 6:e12889. Epub 2019 Jan 6.

Department of Biochemistry and Molecular Medicine and CR-CHUM, Université de Montréal, Montréal, Québec, Canada.

Most cancers arise in old individuals, which also accumulate senescent cells. Cellular senescence can be experimentally induced by expression of oncogenes or telomere shortening during serial passage in culture. In vivo, precursor lesions of several cancer types accumulate senescent cells, which are thought to represent a barrier to malignant progression and a response to the aberrant activation of growth signaling pathways by oncogenes (oncogene toxicity). Read More

Aging Cell 2019 Jan 4:e12899. Epub 2019 Jan 4.

Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota.

Wnt signaling is a well-known molecular pathway in age-related pathogenesis and therapy of disease. While prior studies have mainly focused on Wnt ligands or Wnt activators, the in vivo functions of naturally secreted Wnt inhibitors are not clear, especially in brain aging. Using BubR1 mice as a novel mouse model of accelerated aging, we report that genetic inhibition of sFRP3 restores the reduced body and brain size observed in BubR1 mice. Read More

Aging Cell 2019 Jan 4:e12895. Epub 2019 Jan 4.

College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.

Aging is a major risk factor for many chronic diseases due to increased vulnerability to external stress and susceptibility to disease. Aging is associated with metabolic liver disease such as nonalcoholic fatty liver. In this study, we investigated changes in lipid metabolism during aging in mice and the mechanisms involved. Read More

Aging Cell 2018 Dec 26:e12846. Epub 2018 Dec 26.

Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, Ohio.

The aging process and age-related diseases all involve perturbed energy adaption and impaired ability to cope with adversity. Brain-derived neurotrophic factor (BDNF) in the hypothalamus plays important role in regulation of energy balance. Our previous studies show that recombinant adeno-associated virus (AAV)-mediated hypothalamic BDNF gene transfer alleviates obesity, diabetes, and metabolic syndromes in both diet-induced and genetic models. Read More

Aging Cell 2019 Feb 21;18(1):e12857. Epub 2018 Dec 21.

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

Structural brain asymmetries have been associated with cognition. However, it is not known to what extent neuropsychological parameters and structural laterality covary with aging. Seventy-five subjects drawn from a larger normal aging cohort were evaluated in terms of MRI and neuropsychological parameters at two moments (M1 and M2), 18 months apart. Read More

Aging Cell 2019 Feb 20;18(1):e12890. Epub 2018 Dec 20.

Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island.

Cell-free DNA (cfDNA) is present in the circulating plasma and other body fluids and is known to originate mainly from apoptotic cells. Here, we provide the first in vivo evidence of global and local chromatin changes in human aging by analyzing cfDNA from the blood of individuals of different age groups. Our results show that nucleosome signals inferred from cfDNA are consistent with the redistribution of heterochromatin observed in cellular senescence and aging in other model systems. Read More

Aging Cell 2019 Feb 21;18(1):e12867. Epub 2018 Dec 21.

Department of Medicine, Brody School of Medicine at East Carolina University, Greenville, North Carolina.

Resveratrol (RSV) extends the lifespan of various organisms through activation of sirtuin. However, whether RSV-mediated longevity is entirely dependent upon sirtuin is still controversial. Thus, understanding additional mechanisms concerning the genetic requirements for the biological activity of RSV needs to be clarified to utilize the beneficial effects of RSV. Read More

Aging Cell 2019 Feb 21;18(1):e12856. Epub 2018 Dec 21.

Department of Aging Science and Pharmacology, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.

During normal aging, innate immunity progresses to a chronic state. However, how oxidative stress and chronic neuroinflammation arise during aging remains unclear. In this study, we found that genetic ablation of cathepsin B (CatB) in mice significantly reduced the generation of reactive oxygen species (ROS) and neuroinflammation and improved cognitive impairment during aging. Read More

Aging Cell 2019 Feb 19;18(1):e12862. Epub 2018 Dec 19.

The Institute of Neurology, University College London, London, UK.

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative condition that is invariably fatal, usually within 3 to 5 years of diagnosis. The etiology of ALS remains unresolved and no effective treatments exist. There is therefore a desperate and unmet need for discovery of disease mechanisms to guide novel therapeutic strategies. Read More

Aging Cell 2019 Feb 19;18(1):e12851. Epub 2018 Dec 19.

Center for Cell Signaling, University of Virginia, Charlottesville, Virginia.

The Ran GTPase regulates nuclear import and export by controlling the assembly state of transport complexes. This involves the direct action of RanGTP, which is generated in the nucleus by the chromatin-associated nucleotide exchange factor, RCC1. Ran interactions with RCC1 contribute to formation of a nuclear:cytoplasmic (N:C) Ran protein gradient in interphase cells. Read More

Aging Cell 2019 Feb 17;18(1):e12871. Epub 2018 Dec 17.

Department of Neurology, Biomedical Sciences Graduate Program, and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, California.

Female longevity is observed in humans and much of the animal kingdom, but its causes remain elusive. Using a genetic manipulation that generates XX and XY mice, each with either ovaries or testes, we show that the female XX sex chromosome complement increases survival during aging in male and female mice. In combination with ovaries, it also extends lifespan. Read More

Aging Cell 2019 Feb 13;18(1):e12886. Epub 2018 Dec 13.

The Jackson Laboratory, Bar Harbor, Maine.

Identifying genetic factors that modify an individual's susceptibility to cognitive decline in aging is critical to understanding biological processes involved and mitigating risk associated with a number of age-related disorders. Recently, heterochromatin protein 1 binding protein 3 (Hp1bp3) was identified as a mediator of cognitive aging. Here, we provide a mechanistic explanation for these findings and show that targeted knockdown of Hp1bp3 in the hippocampus by 50%-75% is sufficient to induce cognitive deficits and transcriptional changes reminiscent of those observed in aging and Alzheimer's disease brains. Read More

Aging Cell 2019 Feb 13;18(1):e12854. Epub 2018 Dec 13.

Division of Human Reproduction and Developmental Genetics, The Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

By the end of neurogenesis in Drosophila pupal brain neuroblasts (NBs), nuclear Prospero (Pros) triggers cell cycle exit and terminates NB lifespan. Here, we reveal that in larval brain NBs, an intrinsic mechanism facilitates import and export of Pros across the nuclear envelope via a Ran-mediated nucleocytoplasmic transport system. In rangap mutants, the export of Pros from the nucleus to cytoplasm is impaired and the nucleocytoplasmic transport of Pros becomes one-way traffic, causing an early accumulation of Pros in the nuclei of the larval central brain NBs. Read More

Aging Cell 2019 Feb 12;18(1):e12852. Epub 2018 Dec 12.

Edward A. Doisy Department of Biochemistry and Molecular Biology, St Louis University School of Medicine, St Louis, Missouri.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a devastating premature aging disease. Mouse models have been instrumental for understanding HGPS mechanisms and for testing therapies, which to date have had only marginal benefits in mice and patients. Barriers to developing effective therapies include the unknown etiology of progeria mice early death, seemingly unrelated to the reported atherosclerosis contributing to HGPS patient mortality, and mice not recapitulating the severity of human disease. Read More

Aging Cell 2019 Feb 12;18(1):e12844. Epub 2018 Dec 12.

Bristol Medical School, University of Bristol, Bristol Royal Infirmary, Bristol, UK.

We previously reported pro-survival effects of Wnt3a and Wnt5a proteins in vascular smooth muscle cells (VSMCs). Wnt5a achieved this through induction of Wnt1-inducible signalling pathway protein-1 (WISP-1) consequent to β-catenin/CREB-dependent, TCF-independent, signalling. However, we found that as atherosclerosis advances, although Wnt5a protein was increased, WISP-1 was reduced. Read More

Aging Cell 2019 Feb 12;18(1):e12858. Epub 2018 Dec 12.

Department of Respiratory Medicine, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease with poor prognosis. Currently, there are no effective drugs for preventing the disease process. The mechanisms underlying the role of alveolar epithelial cell (AEC) senescence in the pathogenesis of IPF remain poorly understood. Read More

Aging Cell 2019 Feb 11;18(1):e12880. Epub 2018 Dec 11.

Department of Health and Exercise Science, Colorado State University, Fort Collins, Colorado.

Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise-induced improvement in insulin sensitivity and cardiorespiratory fitness. Read More

Aging Cell 2019 Feb 10;18(1):e12845. Epub 2018 Dec 10.

Department of Cell Biology and Biophysics, Faculty of Biology, National & Kapodistrian University of Athens, Athens, Greece.

Metazoans viability depends on their ability to regulate metabolic processes and also to respond to harmful challenges by mounting anti-stress responses; these adaptations were fundamental forces during evolution. Central to anti-stress responses are a number of short-lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors. We show here that increased expression of nuclear factor erythroid 2-related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance. Read More

Aging Cell 2019 Feb 4;18(1):e12872. Epub 2018 Dec 4.

Department of Biochemistry and Biomedical Sciences, Seoul National University, College of Medicine, Seoul, Korea.

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by progressive memory loss resulting from cumulative neuronal cell death. O-linked β-N-acetyl glucosamine (O-GlcNAc) modification of the proteins reflecting glucose metabolism is altered in the brains of patients with AD. However, the link between altered O-GlcNAc modification and neuronal cell death in AD is poorly understood. Read More

Aging Cell 2019 Feb 4;18(1):e12866. Epub 2018 Dec 4.

Molecular Neurobiology Laboratory, Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts.

The orphan nuclear receptor Nurr1 (also known as NR4A2) is critical for the development and maintenance of midbrain dopaminergic neurons, and is associated with Parkinson's disease. However, an association between Nurr1 and Alzheimer's disease (AD)-related pathology has not previously been reported. Here, we provide evidence that Nurr1 is expressed in a neuron-specific manner in AD-related brain regions; specifically, it is selectively expressed in glutamatergic neurons in the subiculum and the cortex of both normal and AD brains. Read More

Aging Cell 2019 Feb 3;18(1):e12863. Epub 2018 Dec 3.

Department of Ecology and Evolutionary Biology, Brown University, Providence, Rhode Island.

Insulin/IGF signaling (IIS) regulates essential processes including development, metabolism, and aging. The Drosophila genome encodes eight insulin/IGF-like peptide (dilp) paralogs, including tandem-encoded dilp1 and dilp2. Many reports show that longevity is increased by manipulations that decrease DILP2 levels. Read More

Aging Cell 2019 Feb 28;18(1):e12873. Epub 2018 Nov 28.

The Arizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute, Arizona State University, Tempe, Arizona.

Accumulation of amyloid-β (Aβ) and fibrillary tangles, as well as neuroinflammation and memory loss, are hallmarks of Alzheimer's disease (AD). After almost 15 years from their generation, 3xTg-AD mice are still one of the most used transgenic models of AD. Converging evidence indicates that the phenotype of 3xTg-AD mice has shifted over the years and contradicting reports about onset of pathology or cognitive deficits are apparent in the literature. Read More

Aging Cell 2019 Feb 28;18(1):e12860. Epub 2018 Nov 28.

Department of Neurosurgery, Affiliated Bayi Brain Hospital, General Army Hospital, Southern Medical University, Beijing, China.

Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Accumulated damaged mitochondria, which are associated with impaired mitophagy, contribute to neurodegeneration in AD. We show levels of Disrupted-in-schizophrenia-1 (DISC1), which is genetically associated with psychiatric disorders and AD, decrease in the brains of AD patients and transgenic model mice and in Aβ-treated cultured cells. Read More