Ageing articles within Nature Communications

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  • Article
    | Open Access

    Microbiota impacts all major aspects of physiology, but little is known about its effects on age-related changes in immune responses. Here the authors show that gut microbiota transfer between adult and old mice increases local but not systemic germinal centre responses regardless of age directionality.

    • Marisa Stebegg
    • , Alyssa Silva-Cayetano
    •  & Michelle A. Linterman

  • Article
    | Open Access

    Senescent cells increase with ageing and may cause inflammatory conditions, but how this accumulation is mediated is still unclear. Here the authors show that senescent cells express HLA-E to suppress NKG2A-mediated natural killer and CD8 T cell activation to avoid targeted elimination, while blocking NKG2A helps promote immunity against senescent cells.

    • Branca I. Pereira
    • , Oliver P. Devine
    •  & Arne N. Akbar

  • Article
    | Open Access

    Different sensory experiences can affect longevity in Drosophila. Here the authors find that exposure of Drosophila directly to dead conspecifics affects longevity via a serotonergic mechanism, and that Drosophila exposed to dead conspecifics also become an aversive stimulus to naïve choosers.

    • Tuhin S. Chakraborty
    • , Christi M. Gendron
    •  & Scott D. Pletcher

  • Article
    | Open Access

    Post-translational protein modifications can affect lifespan and aging but age-dependent ubiquitylation changes have not yet been systematically characterized. Here, the authors analyze age-related proteome and ubiquitylome dynamics in Drosophila and identify increasing H2A ubiquitylation as a conserved aging marker.

    • Lu Yang
    • , Zaijun Ma
    •  & Yaoyang Zhang

  • Article
    | Open Access

    Sociality explains substantial variation in ageing across species, but less is known about this relationship within species. Here, the authors show that female dominant Seychelles warblers with helpers at the nest have higher late-life survival and lower telomere attrition and the probability of having helpers increases with age.

    • Martijn Hammers
    • , Sjouke A. Kingma
    •  & David S. Richardson

  • Article
    | Open Access

    Protein homeostasis maintenance (proteostasis) is critical for cell function, but declines during aging. Here the authors detail a proteostatic checkpoint in Drosophila intestinal stem cells coordinating cell cycle arrest with protein aggregate clearance, along with its role in aging related intestinal dysfunction.

    • Imilce A. Rodriguez-Fernandez
    • , Yanyan Qi
    •  & Heinrich Jasper

  • Article
    | Open Access

    Aging impacts lung functionality and makes it more susceptible to chronic diseases. Combining proteomics and single cell transcriptomics, the authors chart molecular and cellular changes in the aging mouse lung, discover aging hallmarks, and predict the cellular sources of regulated proteins.

    • Ilias Angelidis
    • , Lukas M. Simon
    •  & Herbert B. Schiller

  • Article
    | Open Access

    Fibroblasts can be directly reprogrammed to cardiomyocytes, but reprogramming is less efficient for adult compared to embryonic fibroblasts. Here, the authors find that inhibition of inflammation and Cox-2-prostaglandin-cAMP-IL-1β signaling enhances reprogramming efficiency of adult, but not embryonic fibroblasts.

    • Naoto Muraoka
    • , Kaori Nara
    •  & Masaki Ieda

  • Article
    | Open Access

    Although ageing is the most important risk factor for chronic ailments, effective interventions remain rare. Here, the authors identify the flavonoid 4,4’-dimethoxychalcone and demonstrate that it extends lifespan and promotes health in multiple organisms by inducing autophagy.

    • Didac Carmona-Gutierrez
    • , Andreas Zimmermann
    •  & Frank Madeo

  • Article
    | Open Access

    While human lifespan is only moderately heritable, “getting old” runs in families. Here, van den Berg et al. study mortality data from three-generation cohorts to define a threshold for longevity and find that individuals have an increasing survival advantage with each additional relative in the top 10% survivors of their birth cohort.

    • Niels van den Berg
    • , Mar Rodríguez-Girondo
    •  & P. Eline Slagboom

  • Article
    | Open Access

    While young muscle faithfully regenerates damaged myofibers, aged muscle is impaired. Here the authors show the “anti-aging” protein α-Klotho is upregulated in young muscle after damage via promoter demethylation and this regulation is lost in aging, resulting in mitochondrial damage and an impaired healing response.

    • A. Sahu
    • , H. Mamiya
    •  & F. Ambrosio

  • Article
    | Open Access

    The transcription factor DAF-16/FOXO is a downstream effector of insulin/insulin-like growth factor signaling and plays an important role in stress resistance and longevity. Here, the authors show that DAF-16/FOXO can form a complex with HLH-30/TFEB to synergistically regulate transcription of target genes in response to certain stress stimuli.

    • Xin-Xuan Lin
    • , Ilke Sen
    •  & Christian G. Riedel

  • Article
    | Open Access

    Ageing causes an inability to replace damaged tissue. Here, the authors perform proteomics analyses of human haematopoietic stem cells and other cells in the bone marrow niche at different ages and show changes in central carbon metabolism, reduced bone marrow niche function, and enhanced myeloid differentiation.

    • Marco L. Hennrich
    • , Natalie Romanov
    •  & Anthony D. Ho

  • Article
    | Open Access

    Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

    • Gabriel Balmus
    • , Delphine Larrieu
    •  & Stephen P. Jackson

  • Article
    | Open Access

    Declining NAD+ levels have been linked to aging-associated pathologies. Here the authors present results of a double-blind, randomized crossover trial on 30 healthy middle-aged individuals to show that nicotinamide riboside effectively elevates NAD+ levels in humans, appears to be well tolerated, and may have potential to improve cardiovascular parameters.

    • Christopher R. Martens
    • , Blair A. Denman
    •  & Douglas R. Seals

  • Article
    | Open Access

    The nematode C. elegans is known to alter its behavior in response to UV light. Here, the authors show that visible light triggers photo-oxidative stress and a wider stress response in C. elegans, suggesting that light exposure during routine laboratory handling may influence the outcome of lifespan experiments.

    • C. Daniel De Magalhaes Filho
    • , Brian Henriquez
    •  & Andrew Dillin

  • Article
    | Open Access

    Aging skeletal muscle shows declining numbers and activity of satellite cells. Here, Franco et al. show that in satellite cells of the human leg muscle vastus lateralis, somatic mutations accumulate with age and that these mutations become enriched in exons and promoters of genes involved in muscle function.

    • Irene Franco
    • , Anna Johansson
    •  & Maria Eriksson

  • Article
    | Open Access

    Ageing is associated with a pronounced shift in mortality from cancer to degenerative diseases. Here, the authors show that in concordance with this shift, conserved transcriptional alterations during ageing across four vertebrates align with degenerative diseases but are opposite to those in cancer.

    • Peer Aramillo Irizar
    • , Sascha Schäuble
    •  & Christoph Kaleta

  • Article
    | Open Access

    Non-circulating, tissue-resident T cells have been reported for non-lymphoid organs, but their characterization and regulation in secondary lymphoid organs (SLO) are still lacking. Here the authors show that age and microbiota both exert SLO-specific effects for the various tissue-resident T cell subsets.

    • Aurélie Durand
    • , Alexandra Audemard-Verger
    •  & Bruno Lucas

  • Article
    | Open Access

    Activation of autophagy, via the transcription factor TFEB, is a promising strategy to treat metabolic diseases. Here, the authors report three novel classes of small molecules that promote TFEB nuclear translocation, and provide evidence for the therapeutic efficacy of these compounds in mice and worms.

    • Chensu Wang
    • , Hanspeter Niederstrasser
    •  & Michael A. White

  • Article
    | Open Access

    Hydralazine is an FDA approved drug for the treatment of hypertension. Here, Dehghan et al. report that hydralazine triggers the cellular oxidative stress response by activating NRF2/SKN-1 signaling and extends C. elegans healthy lifespan, suggesting hydralazine may have potential to treat age-associated diseases more broadly.

    • Esmaeil Dehghan
    • , Yiqiang Zhang
    •  & Hamid Mirzaei

  • Article
    | Open Access

    Changes in chromatin structure have been linked to organismal ageing. Here the authors show that altered histone expression and mitochondrial stress during C. elegans development result in chromatin changes and a cytosolic stress response that affects organismal longevity, and depends on HSF-1 and the chromatin remodeller, ISW-1.

    • Olli Matilainen
    • , Maroun S. Bou Sleiman
    •  & Johan Auwerx

  • Article
    | Open Access

    The diet consumed during development can have long-lasting effects on adult physiology. Here, the authors show that developmental undernutrition in Drosophila extends lifespan by inhibiting the production of toxic lipids, called autotoxins, on the adult body surface.

    • M. Irina Stefana
    • , Paul C. Driscoll
    •  & Alex P. Gould

  • Article
    | Open Access

    KLF family transcription factors (KLFs) regulate many cellular processes, including proliferation, survival and stress responses. Here, the authors position KLFs as important regulators of autophagy and lifespan in C. elegans, a role that may extend to the modulation of age-associated vascular phenotypes in mammals.

    • Paishiun N. Hsieh
    • , Guangjin Zhou
    •  & Mukesh K. Jain

  • Article
    | Open Access

    Repeated cell divisions induce DNA damage in haematopoietic stem cells (HSC) and telomeres are sensitive to this damage. Here, the authors show in murine HSCs that the telomere binding protein POT1a inhibited the production of reactive oxygen species, and rejuvenated aged HSCs.

    • Kentaro Hosokawa
    • , Ben D. MacArthur
    •  & Fumio Arai

  • Article
    | Open Access

    Gene expression is a noisy process, but it is not known how noise in gene expression changes during the aging of single cells. Here the authors show that noise decreases during normal aging, and provide support for aging-associated increases in chromatin state transitions governing noise reduction.

    • Ping Liu
    • , Ruijie Song
    •  & Murat Acar

  • Article
    | Open Access

    Clarifying the source of proteins in mixed biological environments, such as after transplantation or parabiosis, remains a challenge. Here, the authors address this need with a mouse strain that incorporates a methionine derivate into proteins, allowing for their detection using click chemistry and antibody arrays.

    • Yan Liu
    • , Michael J. Conboy
    •  & Irina M. Conboy

  • Article
    | Open Access

    Caloric restriction has been shown to increase lifespan in mammals. Here, the authors provide evidence that age-related methylation drift correlates with lifespan and that caloric restriction in mice and rhesus monkeys results in attenuation of age-related methylation drift.

    • Shinji Maegawa
    • , Yue Lu
    •  & Jean-Pierre J. Issa

  • Article
    | Open Access

    The transcription factor Gcn4 is known to regulate yeast amino acid synthesis. Here, the authors show that Gcn4 also acts as a repressor of protein biosynthesis in a range of conditions that enhance yeast lifespan, such as ribosomal protein knockout, calorie restriction or mTOR inhibition.

    • Nitish Mittal
    • , Joao C. Guimaraes
    •  & Mihaela Zavolan

  • Article
    | Open Access

    Mitochondrial fission and fusion are important mechanisms to maintain mitochondrial function. Here, the authors report that middle-aged flies have more elongated, or ‘hyper-fused’ mitochondria, and show that induction of mitochondrial fission in midlife, but not in early life, extends the health and life of flies.

    • Anil Rana
    • , Matheus P. Oliveira
    •  & David W. Walker

  • Article
    | Open Access

    Advanced maternal age has been associated with lower reproductive success and higher risk of pregnancy complications. Here the authors show that maternal ageing-related embryonic abnormalities in mouse are caused by decidualisation and placentation defects that can be rescued by transferring the embryo from an old to a young uterus.

    • Laura Woods
    • , Vicente Perez-Garcia
    •  & Myriam Hemberger

  • Article
    | Open Access

    The accumulation of senescent cells is thought to contribute to the age-associated decline in tissue function. Here, the authors identify HSP90 inhibitors as a new class of senolytic compounds in an in vitro screening and show that administration of a HSP90 inhibitor reduces age-related symptoms in progeroid mice.

    • Heike Fuhrmann-Stroissnigg
    • , Yuan Yuan Ling
    •  & Paul D. Robbins

  • Article
    | Open Access

    Animal lifespan is plastic and is regulated by conserved signalling pathways. Here, Tikuet al.show that longevity-enhancing mutations or interventions are associated with reduced nucleolar size in worms, flies, mice and humans, and that nucleolar size can predict life-expectancy in individual worms.

    • Varnesh Tiku
    • , Chirag Jain
    •  & Adam Antebi

  • Article
    | Open Access

    HGPS is a premature aging disease caused by mutations in the nuclear protein lamin A. Here, the authors show that cells from patients with HGPS have expanded nucleoli and increased protein synthesis, and report that nucleoli also expand as aging progresses in cells derived from healthy individuals.

    • Abigail Buchwalter
    •  & Martin W. Hetzer

  • Article
    | Open Access

    Alternative splicing coupled to nonsense-mediated decay (AS-NMD) is a conserved mechanism for post-transcriptional gene regulation. Here, the authors provide evidence that AS-NMD is enhanced during dietary restriction (DR) and is required for DR-mediated longevity assurance in C. elegans.

    • Syed Shamsh Tabrez
    • , Ravi Datta Sharma
    •  & Arnab Mukhopadhyay

  • Article
    | Open Access

    Glycogen is a storage form of glucose in cells. Here, Gusarovet al. show that glycogen-derived glucose can be used to quickly regenerate the antioxidant glutathione and that inhibiting glycogen synthesis extends C. eleganslifespan, whereas glycogen accumulation drives organismal ageing in worms.

    • Ivan Gusarov
    • , Bibhusita Pani
    •  & Evgeny Nudler

  • Article
    | Open Access

    Non-alcoholic fatty liver disease is more common among older individuals. Here, the authors show that senescent cells in the liver promote fat accumulation and steatosis in the liver, and that clearance of senescent cells reduces hepatic steatosis in old, obese or diabetic mice.

    • Mikolaj Ogrodnik
    • , Satomi Miwa
    •  & Diana Jurk

  • Article
    | Open Access

    Despite its wide use in ageing research, the contribution of specific age-associated pathologies toC. elegansmortality is not well understood. Here the authors identify two types of death in worms, with either a swollen or a shrunken pharynx, that are differentially affected by age and mutations that extend worm lifespan.

    • Yuan Zhao
    • , Ann F. Gilliat
    •  & David Gems

  • Article
    | Open Access

    Germline mutation rates are known to vary between species but somatic mutation rates are less well understood. Here the authors compare mice and humans, observing that somatic mutation rates were nearly two orders of magnitude higher in both species, with both mutation rates significantly higher in mice.

    • Brandon Milholland
    • , Xiao Dong
    •  & Jan Vijg

  • Article
    | Open Access

    The decline of DNA and protein quality control contributes to organismal ageing. Here, Sonet al. report that nonsense-mediated mRNA decay, a RNA quality control mechanism, is enhanced in long-lived daf-2 mutant worms and contributes to their longevity by regulating expression of the yars-2/tyrosyl tRNA synthetase.

    • Heehwa G. Son
    • , Mihwa Seo
    •  & Seung-Jae V. Lee

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