Search Our Scientific Publications & Authors

Aging Cell 2020 Jul 7:e13183. Epub 2020 Jul 7.

Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, Leioa, Spain.

Osteopontin (OPN), a senescence-associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated with age-dependent hepatosteatosis. Thus, we investigated the role of OPN in the age-related hepatosteatosis. Read More

Aging Cell 2020 Jul 6:e13179. Epub 2020 Jul 6.

Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.

Brain function has been implicated to control the aging process and modulate lifespan. However, continuous efforts remain for the identification of the minimal sufficient brain region and the underlying mechanism for neuronal regulation of longevity. Here, we show that the Drosophila lifespan is modulated by rab27 functioning in a small subset of neurons of the mushroom bodies (MB), a brain structure that shares analogous functions with mammalian hippocampus and hypothalamus. Read More

Aging Cell 2020 Jul 6:e13187. Epub 2020 Jul 6.

Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA.

Advancing age is a major risk factor for developing heart disease, and the biological processes contributing to aging are currently under intense investigation. Autophagy is an important cellular quality control mechanism that is reduced in tissues with age but the molecular mechanisms underlying the age-associated defects in autophagy remain poorly characterized. Here, we have investigated how the autophagic process is altered in aged mouse hearts. Read More

Aging Cell 2020 Jul 1:e13178. Epub 2020 Jul 1.

Fertility Labs of Colorado, Lone Tree, CO, USA.

Paternal aging and the prevalence of neurodevelopmental disorders in offspring are well documented. Yet, the underlying mechanism and the mode of inheritance have not been conclusively established. Advancing paternal age is a subtle and varying phenotype. Read More

Aging Cell 2020 Jul 1:e13181. Epub 2020 Jul 1.

Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.

In somatic cells/tissues, methylation of ribosomal DNA (rDNA) increases with age and age-related pathologies, which has a direct impact on the regulation of nucleolar activity and cellular metabolism. Here, we used bisulfite pyrosequencing and show that methylation of the rDNA transcription unit including upstream control element (UCE), core promoter, 18S rDNA, and 28S rDNA in human sperm also significantly increases with donor's age. This positive correlation between sperm rDNA methylation and biological age is evolutionarily conserved among mammals with widely different life spans such as humans, marmoset, bovine, and mouse. Read More

Aging Cell 2020 Jun 29:e13161. Epub 2020 Jun 29.

INSERM UMR 1215, Magendie Neurocenter, Neurogenesis and Pathophysiology Group, Bordeaux, France.

During aging, some individuals are resilient to the decline of cognitive functions whereas others are vulnerable. These inter-individual differences in memory abilities have been associated with differences in the rate of hippocampal neurogenesis measured in elderlies. Whether the maintenance of the functionality of neurons generated throughout adult life is linked to resilience to cognitive aging remains completely unexplored. Read More

Aging Cell 2020 Jun 28:e13175. Epub 2020 Jun 28.

Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong Special Administrative Region, China.

Hutchinson-Gilford progeria syndrome (HGPS) is an autosomal-dominant genetic disease that leads to accelerated aging and often premature death caused by cardiovascular complications. Till now clinical management of HGPS has largely relied on the treatment of manifestations and on the prevention of secondary complications, cure for the disease has not yet been established. Addressing this need cannot only benefit progeria patients but may also provide insights into intervention design for combating physiological aging. Read More

Aging Cell 2020 Jun 22. Epub 2020 Jun 22.

Animal Science Laboratory, Orentreich Foundation for the Advancement of Science, NY, USA.

Trade-offs in life-history traits are clinically and mechanistically important. Sulfur amino acid restriction (SAAR) extends lifespan. But whether this benefit comes at the cost of other traits including stress resistance and growth is unclear. Read More

Aging Cell 2020 Jun 22. Epub 2020 Jun 22.

Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.

Senescent cells may possess the intrinsic programs of metabolic and epigenomic remodeling, but the molecular mechanism remains to be clarified. Using an RNAi-based screen of chromatin regulators, we found that knockdown of the NSD2/WHSC1/MMSET methyltransferase induced cellular senescence that augmented mitochondrial mass and oxidative phosphorylation in primary human fibroblasts. Transcriptome analysis showed that loss of NSD2 downregulated the expression of cell cycle-related genes in a retinoblastoma protein (RB)-mediated manner. Read More

Aging Cell 2020 Jun 21. Epub 2020 Jun 21.

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

Oxoaldehyde stress has recently emerged as a major source of tissue damage in aging and age-related diseases. The prevailing mechanism involves methylglyoxal production during glycolysis and modification of arginine residues through the formation of methylglyoxal hydroimidazolones (MG-H1). We now tested the hypothesis that oxidation of vitamin C (ascorbic acid or ASA) contributes to this damage when the homeostatic redox balance is disrupted especially in ASA-rich tissues such as the eye lens and brain. Read More

Aging Cell 2020 Jun 21. Epub 2020 Jun 21.

Ferguson Laboratory for Orthopedic and Spine Research, Department of Orthopedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.

Previously, we reported that persistent DNA damage accelerates ageing of the spine, but the mechanisms behind this process are not well understood. Ataxia telangiectasia mutated (ATM) is a protein kinase involved in the DNA damage response, which controls cell fate, including cell death. To test the role of ATM in the human intervertebral disc, we exposed human nucleus pulposus (hNP) cells directly to the DNA damaging agent cisplatin. Read More

Aging Cell 2020 Jun 19. Epub 2020 Jun 19.

Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON, Canada.

While cell therapy is emerging as a promising option for patients with ischemic cardiomyopathy (ICM), the influence of advanced donor age and a history of ischemic injury on the reparative performance of these cells are not well defined. As such, intrinsic changes that result from advanced donor age and ischemia are explored in hopes of identifying a molecular candidate capable of restoring the lost reparative potency of heart explant-derived cells (EDCs) used in cell therapy. EDCs were cultured from myocardial biopsies obtained from young or old mice 4 weeks after randomization to experimental myocardial infarction or no intervention. Read More

Aging Cell 2020 Jun 19. Epub 2020 Jun 19.

Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology (CQB), Peking University, Beijing, China.

The COVID-19 coronavirus is now spreading worldwide. Its pathogen, SARS-CoV-2, has been shown to use angiotensin-converting enzyme 2 (ACE2) as its host cell receptor, same as the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003. Epidemiology studies found males although only slightly more likely to be infected than females account for the majority of the severely ill and fatality, which also bias for people older than 60 years or with metabolic and cardiovascular diseases. Read More

Aging Cell 2020 Jun 14:e13164. Epub 2020 Jun 14.

Department of Surgery, Stanford Medicine, Stanford, CA, USA.

Fragility fractures have a limited capacity to regenerate, and impaired fracture healing is a leading cause of morbidity in the elderly. The recent identification of a highly purified bona fide human skeletal stem cell (hSSC) and its committed downstream progenitor cell populations provides an opportunity for understanding the mechanism of age-related compromised fracture healing from the stem cell perspective. In this study, we tested whether hSSCs isolated from geriatric fractures demonstrate intrinsic functional defects that drive impaired healing. Read More

Aging Cell 2020 Jun 14:e13172. Epub 2020 Jun 14.

Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.

The number, size, and composition of lipid droplets can be influenced by dietary changes that shift energy substrate availability. This diversification of lipid droplets can promote metabolic flexibility and shape cellular stress responses in unique tissues with distinctive metabolic roles. Using Drosophila, we uncovered a role for myocyte enhancer factor 2 (MEF2) in modulating diet-dependent lipid droplet diversification within adult striated muscle, impacting mortality rates. Read More

Aging Cell 2020 Jun 9. Epub 2020 Jun 9.

The Shraga Segal Department of Microbiology, Immunology and Genetics, Center for Multidisciplinary Research on Aging, Ben-Gurion University of the Negev, Beer Sheva, Israel.

One important question in aging research is how differences in genomics and transcriptomics determine the maximum lifespan in various species. Despite recent progress, much is still unclear on the topic, partly due to the lack of samples in nonmodel organisms and due to challenges in direct comparisons of transcriptomes from different species. The novel ranking-based method that we employ here is used to analyze gene expression in the gray whale and compare its de novo assembled transcriptome with that of other long- and short-lived mammals. Read More

Aging Cell 2020 Jun 5. Epub 2020 Jun 5.

Department of Health and Exercise Science, Center for Healthy Aging, Colorado State University, Fort Collins, CO, USA.

Transcriptomic markers of aging can be useful for studying age-related processes and diseases. However, noncoding repetitive element (RE) transcripts, which may play an important role in aging, are commonly overlooked in transcriptome studies-and their potential as a transcriptomic marker of aging has not been evaluated. Here, we used multiple RNA-seq datasets generated from human samples and Caenorhabditis elegans and found that most RE transcripts (a) accumulate progressively with aging; (b) can be used to accurately predict age; and (c) may be a good marker of biological age. Read More

Aging Cell 2020 Jun 4. Epub 2020 Jun 4.

Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.

Microtubule-associated protein Tau, abundant in the central nervous system (CNS), plays crucial roles in microtubule assembly and stabilization. Abnormal Tau phosphorylation and aggregation are a common pathogenic hallmark in Alzheimer's disease (AD). Hyperphosphorylation of Tau could change its conformation and result in self-aggregation, increased oxidative stress, and neuronal death. Read More

Aging Cell 2020 Jun 31;19(6):e13150. Epub 2020 May 31.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, South Korea.

Excessive glucose causes various diseases and decreases lifespan by altering metabolic processes, but underlying mechanisms remain incompletely understood. Here, we show that Lipin 1/LPIN-1, a phosphatidic acid phosphatase and a putative transcriptional coregulator, prevents life-shortening effects of dietary glucose on Caenorhabditis elegans. We found that depletion of lpin-1 decreased overall lipid levels, despite increasing the expression of genes that promote fat synthesis and desaturation, and downregulation of lipolysis. Read More

Aging Cell 2020 Jun 31;19(6):e13163. Epub 2020 May 31.

Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China.

Poly (ADP-ribose) polymerase 1 (PARP1) is a master regulator of diverse biological processes such as DNA repair, oxidative stress, and apoptosis. PARP1 can be activated by aggregated α-synuclein, and this process in turn exacerbates toxicity of α-synuclein. This circle is closely linked to the evolution of Parkinson's disease (PD) that characterized by progressive neurodegeneration and motor deficits. Read More

Aging Cell 2020 Jun 28;19(6):e13135. Epub 2020 May 28.

AdventHealth Translational Research Institute, Orlando, FL, USA.

The loss of skeletal muscle mass and function with age (sarcopenia) is a critical healthcare challenge for older adults. 31-phosphorus magnetic resonance spectroscopy ( P-MRS) is a powerful tool used to evaluate phosphorus metabolite levels in muscle. Here, we sought to determine which phosphorus metabolites were linked with reduced muscle mass and function in older adults. Read More

Aging Cell 2020 Jun 28;19(6):e13156. Epub 2020 May 28.

Pharmaceutical Biology, Department of Pharmacy, Saarland University, Saarbrücken, Germany.

The aging process is characterized by a chronic, low-grade inflammatory state, termed "inflammaging." It has been suggested that macrophage activation plays a key role in the induction and maintenance of this state. In the present study, we aimed to elucidate the mechanisms responsible for aging-associated changes in the myeloid compartment of mice. Read More

Aging Cell 2020 May;19(5):e13165

Aging Cell 2020 Jun 25;19(6):e13151. Epub 2020 May 25.

Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Korea.

Glucose controls the phosphorylation of silent information regulator 2 (Sir2), a NAD -dependent protein deacetylase, which regulates the expression of the ATP-dependent proton pump Pma1 and replicative lifespan (RLS) in yeast. TORC1 signaling, which is a central regulator of cell growth and lifespan, is regulated by glucose as well as nitrogen sources. In this study, we demonstrate that TORC1 signaling controls Sir2 phosphorylation through casein kinase 2 (CK2) to regulate PMA1 expression and cytoplasmic pH (pHc) in yeast. Read More

Aging Cell 2020 Jun 22;19(6):e13159. Epub 2020 May 22.

Corrigan Minehan Heart Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Heart failure with preserved ejection fraction (HFpEF) is the most common type of HF in older adults. Although no pharmacological therapy has yet improved survival in HFpEF, exercise training (ExT) has emerged as the most effective intervention to improving functional outcomes in this age-related disease. The molecular mechanisms by which ExT induces its beneficial effects in HFpEF, however, remain largely unknown. Read More

Aging Cell 2020 Jun 20;19(6):e13157. Epub 2020 May 20.

Institute of Biopharmaceutical Sciences, Yang-Ming University, Taipei, Taiwan.

Stress granules (SGs) are nonmembranous organelles that are dynamically assembled and disassembled in response to various stressors. Under stressed conditions, polyadenylated mRNAs and translation factors are sequestrated in SGs to promote global repression of protein synthesis. It has been previously demonstrated that SG formation enhances cell survival and stress resistance. Read More

Aging Cell 2020 Jun 20;19(6):e13160. Epub 2020 May 20.

Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.

The G protein-coupled receptor (GPCR) encoding family of genes constitutes more than 6% of genes in Caenorhabditis elegans genome. GPCRs control behavior, innate immunity, chemotaxis, and food search behavior. Here, we show that C. Read More

Aging Cell 2020 Jun 17;19(6):e13153. Epub 2020 May 17.

Veteran's Affairs Boston Healthcare System, Boston, MA, USA.

The pathogenesis of Alzheimer's disease (AD) and the commonest cause of dementia in the elderly remain incompletely understood. Recently, epigenetic modifications have been shown to play a potential role in neurodegeneration, but the specific involvement of epigenetic signatures landscaped by heterochromatin has not been studied in AD. Herein, we discovered that H3K9me3-mediated heterochromatin condensation is elevated in the cortex of sporadic AD postmortem brains. Read More

Aging Cell 2020 Jun 13;19(6):e13154. Epub 2020 May 13.

Department of Pathology, Carver College of Medicine, University of Iowa, Iowa City, Iowa.

This study investigated the direct roles of hydrogen peroxide (H O ) in kidney aging using transgenic mice overexpressing glutathione peroxidase-1 (GPX1 TG). We demonstrated that kidneys in old mice recapitulated kidneys in elderly humans and were characterized by glomerulosclerosis, tubular atrophy, interstitial fibrosis, and loss of cortical mass. Scavenging H O by GPX1 TG significantly reduced mitochondrial and total cellular reactive oxygen species (ROS) and mitigated oxidative damage, thus improving these pathologies. Read More

Aging Cell 2020 Jun 3;19(6):e13149. Epub 2020 May 3.

MRC Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

Markers of biological aging have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry in urine and serum, within a large sample (N = 2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. Read More

Aging Cell 2020 Jun 30;19(6):e13139. Epub 2020 Apr 30.

Section of Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.

Loci associated with longevity are likely to harbor genes coding for key players of molecular pathways involved in a lifelong decreased mortality and decreased/compressed morbidity. However, identifying such loci is challenging. One of the most plausible reasons is the uncertainty in defining long-lived cases with the heritable longevity trait among long-living phenocopies. Read More

Aging Cell 2020 Jun 29;19(6):e13147. Epub 2020 Apr 29.

Shenzhen Key Laboratory for Systemic Aging and Intervention (SAI), National Engineering Research Center for Biotechnology (Shenzhen), Medical Research Center, Shenzhen University Health Science Center, Shenzhen, China.

Progerin accumulation disrupts nuclear lamina integrity and causes nuclear structure abnormalities, leading to premature aging, that is, Hutchinson-Gilford progeria syndrome (HGPS). The roles of nuclear subcompartments, such as PML nuclear bodies (PML NBs), in HGPS pathogenesis, are unclear. Here, we show that classical dot-like PML NBs are reorganized into thread-like structures in HGPS patient fibroblasts and their presence is associated with late stage of senescence. Read More

Aging Cell 2020 May 23;19(5):e13119. Epub 2020 Apr 23.

Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Aging involves coordinated yet distinct changes in organs and systems throughout life, including changes in essential trace elements. However, how aging affects tissue element composition (ionome) and how these changes lead to dysfunction and disease remain unclear. Here, we quantified changes in the ionome across eight organs and 16 age groups of mice. Read More

Aging Cell 2020 May 22;19(5):e13145. Epub 2020 Apr 22.

Institute of Life Sciences, Jiangsu University, Zhenjiang, China.

It is well established that inflammation in the body promotes organism aging, and recent studies have attributed a similar effect to senescent cells. Considering that certain pro-inflammatory cytokines can induce cellular senescence, systematically evaluating the effects of pro-inflammatory cytokines in cellular senescence is an important and urgent scientific problem, especially given the ongoing surge in aging human populations. Treating IMR90 cells and HUVECs with pro-inflammatory cytokines identified six factors able to efficiently induce cellular senescence. Read More

Aging Cell 2020 May 22;19(5):e13116. Epub 2020 Apr 22.

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.

WRN mutation causes a premature aging disease called Werner syndrome (WS). However, the mechanism by which WRN loss leads to progeroid features evident with impaired tissue repair and regeneration remains unclear. To determine this mechanism, we performed gene editing in reprogrammed induced pluripotent stem cells (iPSCs) derived from WS fibroblasts. Read More

Aging Cell 2020 May 22;19(5):e13148. Epub 2020 Apr 22.

Department of Orthopedic Surgery, Sidney Kimmel Medical College, Philadelphia, PA, USA.

Intervertebral disc degeneration presents a wide spectrum of clinically degenerative disc phenotypes; however, the contribution of genetic background to the degenerative outcomes has not been established. We characterized the spinal phenotype of 3 mouse strains with varying cartilage-regenerative potential at 6 and 23 months: C57BL/6, LG/J and SM/J. All strains showed different aging phenotypes. Read More

Aging Cell 2020 May 19;19(5):e13146. Epub 2020 Apr 19.

Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

Age-dependent cognitive and behavioral deterioration may arise from defects in different components of the nervous system, including those of neurons, synapses, glial cells, or a combination of them. We find that AFD, the primary thermosensory neuron of Caenorhabditis elegans, in aged animals is characterized by loss of sensory ending integrity, including reduced actin-based microvilli abundance and aggregation of thermosensory guanylyl cyclases. At the functional level, AFD neurons in aged animals are hypersensitive to high temperatures and show sustained sensory-evoked calcium dynamics, resulting in a prolonged operating range. Read More

Aging Cell 2020 May 16;19(5):e13141. Epub 2020 Apr 16.

Institute of Healthy Ageing, and Research Department of Genetics, Evolution and Environment, University College London, London, UK.

In the nematode Caenorhabditis elegans, loss of function of many genes leads to increases in lifespan, sometimes of a very large magnitude. Could this reflect the occurrence of programmed death that, like apoptosis of cells, promotes fitness? The notion that programmed death evolves as a mechanism to remove worn out, old individuals in order to increase food availability for kin is not supported by classic evolutionary theory for most species. However, it may apply in organisms with colonies of closely related individuals such as C. Read More

Aging Cell 2020 May 15;19(5):e13137. Epub 2020 Apr 15.

Department of Genetics, Evolution and Environment, Institute of Healthy Ageing, University College London, London, UK.

Inhibition of signalling through several receptor tyrosine kinases (RTKs), including the insulin-like growth factor receptor and its orthologues, extends healthy lifespan in organisms from diverse evolutionary taxa. This raises the possibility that other RTKs, including those already well studied for their roles in cancer and developmental biology, could be promising targets for extending healthy lifespan. Here, we focus on anaplastic lymphoma kinase (Alk), an RTK with established roles in nervous system development and in multiple cancers, but whose effects on aging remain unclear. Read More

Aging Cell 2020 May 15;19(5):e13143. Epub 2020 Apr 15.

Neuroscience and Signaling Laboratory, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.

The nuclear envelope (NE) is the central organizing unit of the eukaryotic cell serving as a genome protective barrier and mechanotransduction interface between the cytoplasm and the nucleus. The NE is mainly composed of a nuclear lamina and a double membrane connected at specific points where the nuclear pore complexes (NPCs) form. Physiological aging might be generically defined as a functional decline across lifespan observed from the cellular to organismal level. Read More

Aging Cell 2020 Apr 15;19(4):e13140. Epub 2020 Apr 15.

Discipline of Physiology, School of Medicine, National University of Ireland, Galway, Ireland.

One of the key mechanisms underlying skeletal muscle functional deterioration during aging is disrupted mitochondrial dynamics. Regulation of mitochondrial dynamics is essential to maintain a healthy mitochondrial population and prevent the accumulation of damaged mitochondria; however, the regulatory mechanisms are poorly understood. We demonstrated loss of mitochondrial content and disrupted mitochondrial dynamics in muscle during aging concomitant with dysregulation of miR-181a target interactions. Read More

Aging Cell 2020 May 31;19(5):e13107. Epub 2020 Mar 31.

Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan.

In mammals, microRNAs can be actively secreted from cells to blood. miR-29b-3p has been shown to play a pivotal role in muscle atrophy, but its role in intercellular communication is largely unknown. Here, we showed that miR-29b-3p was upregulated in normal and premature aging mouse muscle and plasma. Read More

Aging Cell 2020 Apr 31;19(4):e13142. Epub 2020 Mar 31.

CRUK Cambridge Centre Early Detection Programme, Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK.

Pharmacologically active compounds with preferential cytotoxic activity for senescent cells, known as senolytics, can ameliorate or even revert pathological manifestations of senescence in numerous preclinical mouse disease models, including cancer models. However, translation of senolytic therapies to human disease is hampered by their suboptimal specificity for senescent cells and important toxicities that narrow their therapeutic windows. We have previously shown that the high levels of senescence-associated lysosomal β-galactosidase (SA-β-gal) found within senescent cells can be exploited to specifically release tracers and cytotoxic cargoes from galactose-encapsulated nanoparticles within these cells. Read More

Aging Cell 2020 May 28;19(5):e13144. Epub 2020 Mar 28.

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

Recently, we have reported that dentate mossy cells (MCs) control memory precision via directly and functionally innervating local somatostatin (SST) inhibitory interneurons. Here, we report a discovery that dysfunction of synaptic transmission between MCs and SST cells causes memory imprecision in a mouse model of early Alzheimer's disease (AD). Single-cell RNA sequencing reveals that miR-128 that binds to a 3'UTR of STIM2 and inhibits STIM2 translation is increasingly expressed in MCs from AD mice. Read More

Aging Cell 2020 May 25;19(5):e13114. Epub 2020 Mar 25.

Department of Orthopaedics, the Second Affiliated Hospital of Soochow University, Suzhou, China.

Hematopoietic disorders are known to increase the risk of complications such as osteoporosis. However, a direct link between hematopoietic cellular disorders and osteoporosis has been elusive. Here, we demonstrate that the deterioration of hematopoietic autophagy is coupled with osteoporosis in humans. Read More

Aging Cell 2020 Apr 20;19(4):e13122. Epub 2020 Mar 20.

Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR 5286, Centre Léon Bérard, Université de Lyon, Lyon, France.

Hutchinson-Gilford progeria syndrome (HGPS) is caused by an LMNA mutation that results in the production of the abnormal progerin protein. Children with HGPS display phenotypes of premature aging and have an average lifespan of 13 years. We found earlier that the targeting of the transmembrane protein PLA2R1 overcomes senescence and improves phenotypes in a mouse model of progeria. Read More

Aging Cell 2020 Apr 20;19(4):e13124. Epub 2020 Mar 20.

Translational Gerontology Branch, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.

Adequate support of energy for biological activities and during fluctuation of energetic demand is crucial for healthy aging; however, mechanisms for energy decline as well as compensatory mechanisms that counteract such decline remain unclear. We conducted a discovery proteomic study of skeletal muscle in 57 healthy adults (22 women and 35 men; aged 23-87 years) to identify proteins overrepresented and underrepresented with better muscle oxidative capacity, a robust measure of in vivo mitochondrial function, independent of age, sex, and physical activity. Muscle oxidative capacity was assessed by P magnetic resonance spectroscopy postexercise phosphocreatine (PCr) recovery time (τ ) in the vastus lateralis muscle, with smaller τ values reflecting better oxidative capacity. Read More

Aging Cell 2020 Apr 20;19(4):e13128. Epub 2020 Mar 20.

Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China.

Aging impairs the functions of human mesenchymal stem cells (MSCs), thereby severely reducing their beneficial effects on myocardial infarction (MI). MicroRNAs (miRNAs) play crucial roles in regulating the senescence of MSCs; however, the underlying mechanisms remain unclear. Here, we investigated the significance of miR-155-5p in regulating MSC senescence and whether inhibition of miR-155-5p could rejuvenate aged MSCs (AMSCs) to enhance their therapeutic efficacy for MI. Read More

Aging Cell 2020 Apr 18;19(4):e13134. Epub 2020 Mar 18.

Experimental and Clinical Research Center (ECRC), a joint cooperation between the Charité Medical Faculty and the Max Delbrück Center for Molecular Medicine (MDC), Charité - Universitätsmedizin Berlin, Berlin, Germany.

Caveolae position Ca 3.2 (T-type Ca channel encoded by the α-3.2 subunit) sufficiently close to RyR (ryanodine receptors) for extracellular Ca influx to trigger Ca sparks and large-conductance Ca -activated K channel feedback in vascular smooth muscle. Read More

Aging Cell 2020 Apr 16;19(4):e13133. Epub 2020 Mar 16.

MRC London Institute of Medical Sciences (LMS), London, UK.

Senescence is a stable growth arrest that impairs the replication of damaged, old or preneoplastic cells, therefore contributing to tissue homeostasis. Senescent cells accumulate during ageing and are associated with cancer, fibrosis and many age-related pathologies. Recent evidence suggests that the selective elimination of senescent cells can be effective on the treatment of many of these senescence-associated diseases. Read More