Ageing articles within Nature Communications

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  • Article
    | Open Access

    Cellular senescence and associated secretory phenotype (SASP) are thought to contribute to aging and tissue dysfunction, though it is unclear how SASP impacts regeneration. Here the authors show that SASP factors impair regeneration, and that Ptk7 is a key secreted protein mediating that dysregulation.

    • Jina Yun
    • , Simon Hansen
    •  & Heinrich Jasper

  • Article
    | Open Access

    The group of Shih-Yin Tsai observed age-associated neuromuscular junction structural instability in male but not female mice which is driven by dysregulation of mTOR complex 1 activity. Genetic activation of the downstream phosphorylation target 4EBP1 in the muscle remodeled the neuromuscular junction and enhanced synaptic transmission.

    • Seok-Ting J. Ang
    • , Elisa M. Crombie
    •  & Shih-Yin Tsai

  • Article
    | Open Access

    Myelodysplastic syndromes (MDS) are age-related pathologies in which alterations of hematopoietic stem cells lead to abnormal formation of blood cells. Here, the authors study the lesions that these cells undergo in aging and disease, characterizing a factor whose alteration in MDS leads to abnormal blood cell production.

    • Nerea Berastegui
    • , Marina Ainciburu
    •  & Felipe Prosper

  • Article
    | Open Access

    Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.

    • Jie Sun
    • , Ming Wang
    •  & Baohua Liu

  • Article
    | Open Access

    Lifespan can be affected by both physiological ageing and specific sets of pathologies associated with old age. Here the authors report a resource of large-scale cross-sectional phenotyping of aging male mice at different time points to analyse a large set of phenotypes and molecular markers, including during genetic and diet interventions affecting lifespan.

    • Kan Xie
    • , Helmut Fuchs
    •  & Dan Ehninger

  • Article
    | Open Access

    Ageing has been associated with impaired function of alveolar macrophages and increased susceptibility, mortality and complications as a result of viral infection. Here, the authors show that prostaglandin E2 is one of the factors responsible for impairing immune defences against influenza during ageing.

    • Judy Chen
    • , Jane C. Deng
    •  & Daniel R. Goldstein

  • Article
    | Open Access

    Biomarkers of age and frailty may aid in understanding the aging process, predicting lifespan or health span and in assessing the effects of anti-aging interventions. Here, the authors show that combining physics-based models and deep learning may enhance understanding of aging from big biomedical data, observe effects of anti-aging interventions in laboratory animals, and discover signatures of longevity.

    • Konstantin Avchaciov
    • , Marina P. Antoch
    •  & Peter O. Fedichev

  • Article
    | Open Access

    How bone-related sexually dimorphic traits are regulated hasn’t been examined at the stem cell level. Here the authors show that skeletal stem cells (SSC), in female but not male mice, are directly controlled by estrogen signaling, which could be augmented to improve fracture repair.

    • Tom W. Andrew
    • , Lauren S. Koepke
    •  & Charles K. F. Chan

  • Article
    | Open Access

    Selective elimination of senescent cells is an approach that has shown promise to ameliorate age-associated pathologies in preclinical models. Here the authors report that BDNF enhances senescent cell viability via TrkB in cultured cells, and that TrkB inhibition can reduce the accumulation of senescent cells in aged mouse organs.

    • Carlos Anerillas
    • , Allison B. Herman
    •  & Myriam Gorospe

  • Article
    | Open Access

    Sasako et al. show that disruption of the insulin/IGF-1 signaling by suppressing Akt activity in mouse skeletal muscle can accelerate osteosarcopenia and shortens lifespan, which is reversed by inactivation of FoxOs rather than activation of mTOR, suggesting FoxOs as therapeutic targets.

    • Takayoshi Sasako
    • , Toshihiro Umehara
    •  & Kohjiro Ueki

  • Article
    | Open Access

    The precise boundaries and flow compartments of perivascular spaces in the brain are incompletely understood. Here the authors show that pia is perforated and permissive to CSF flow, forming three types of perivascular spaces that remodel with age, with an abnormal type arising in Alzheimer’s disease and correlating with β-amyloid burden and differential macrophage uptake.

    • Humberto Mestre
    • , Natasha Verma
    •  & Rupal I. Mehta

  • Article
    | Open Access

    This report finds that dietary restriction, the most extensively studied anti-aging intervention, can be mimicked by blocking food odour signaling and identifies a neural network of food perception that functions through serotonin and dopamine.

    • Hillary A. Miller
    • , Shijiao Huang
    •  & Scott F. Leiser

  • Article
    | Open Access

    Circadian dysfunction is a potential driver of eye aging. Here the authors report that in conjunction with the core molecular clock transcription factor Clock, dietary restriction promotes rhythmic homeostatic mechanisms within photoreceptors to delay visual senescence and extend lifespan in Drosophila Melanogaster.

    • Brian A. Hodge
    • , Geoffrey T. Meyerhof
    •  & Pankaj Kapahi

  • Article
    | Open Access

    Haematopoietic stem cells (HSCs) exhibit considerable cell-intrinsic changes with age. Here the authors demonstrate that differentially accessible regions in aged HSC chromatin are enriched for stress-responsive enhancers and act as an epigenetic hub to augment transcriptional responses of aged HSCs to external stimuli.

    • Naoki Itokawa
    • , Motohiko Oshima
    •  & Atsushi Iwama

  • Article
    | Open Access

    Age is a risk factor for SARS-CoV-2 infection and severe disease. Here the authors perform DNA methylation analyses in whole blood from COVID-19 patients using established epigenetic clocks and telomere length estimators, and describing correlations between epigenetic aging and the risk of SARS-CoV-2 infection and severe disease.

    • Xue Cao
    • , Wenjuan Li
    •  & Huichuan Yu

  • Article
    | Open Access

    The decline in neurogenesis following birth is accompanied with a quiescent state characteristic of neural progenitors of the adult brain. Here, the authors identify the Wnt pathway antagonist SFRP1 as a potential signal that promotes quiescence and show that its inhibition stimulates stem cell activation.

    • Vanessa Donega
    • , Astrid T. van der Geest
    •  & Elly M. Hol

  • Article
    | Open Access

    Drosophila enter adult reproductive diapause in low temperatures and short day, halting ovarian development yet preserving fertility. Here the authors show that ovarian arrest in diapause is distinct from other stress responses and that despite DNA damage and decreased division, germline stem cells recover.

    • Sreesankar Easwaran
    • , Matthew Van Ligten
    •  & Denise J. Montell

  • Article
    | Open Access

    A decline of selection with age is generally seen as the reason that ageing evolves. But selection can also increase with age. What happens then? This work shows that ageing nevertheless evolves, and so does the decline of selection with age.

    • Stefano Giaimo
    •  & Arne Traulsen

  • Article
    | Open Access

    The exceptionally long-lived naked mole-rat is characterized by the lack of increased mortality with aging. Here the authors perform epigenetic studies to show that naked mole-rats epigenetically age despite their non-increasing mortality rate.

    • Csaba Kerepesi
    • , Margarita V. Meer
    •  & Vadim N. Gladyshev

  • Article
    | Open Access

    Ageing is a known risk factor in the development of cancers, but its association with molecular alterations is not fully explored. Here, the authors analyse pan-cancer age-associated molecular alterations in datasets from the TCGA, PCAWG and AACR-GENIE projects and identify prognostic biomarkers.

    • Constance H. Li
    • , Syed Haider
    •  & Paul C. Boutros

  • Article
    | Open Access

    Methylation levels of specific sites in the genome is correlated with aging. Here the authors develop a human-horse clock which could assist in translating anti-aging interventions from humans to horses and vice versa.

    • Steve Horvath
    • , Amin Haghani
    •  & Carrie J. Finno

  • Article
    | Open Access

    Life- and healthspan of organisms can be modulated by dietary, genetic, or pharmacological interventions, which often affect metabolic pathways. Here the authors report that Grainyhead 1 is an evolutionarily conserved, drug-inducible transcription factor that promotes longevity in C. elegans, and thus a potential target for the development of geroprotective drugs.

    • Giovanna Grigolon
    • , Elisa Araldi
    •  & Fabian Fischer

  • Article
    | Open Access

    Muscle undergoes hypertrophy and atrophy in response to physiological stimuli or in pathological conditions, which is partially controlled through altered gene expression. Here the authors report that m6A methyltransferase METTL3 and mRNA m6A post-transcriptional modifications as a mechanism that regulates muscle hypertrophy and atrophy via myostatin signalling in mice.

    • Jennifer M. Petrosino
    • , Scott A. Hinger
    •  & Federica Accornero

  • Article
    | Open Access

    Understanding the contribution of diet composition, calories and length of fasting in health maintenance is still challenging. Here the authors compare the effects of cycles of intermittent very low calorie intake achieved with a plant-based fasting mimicking diet or standard laboratory chow to provide insights into the role played by diet composition in mediating the metabolic benefits of short cycles of very low-calorie intake in mice.

    • Alberto Diaz-Ruiz
    • , Tyler Rhinesmith
    •  & Rafael de Cabo

  • Article
    | Open Access

    Age is associated with increasing vulnerability to both acute and chronic lung diseases. Employing genomic analysis and live lung imaging, this study reveals a profile of increased cellular senescence, telomere shortening, and fibrosis-induced impaired alveolar function in the natural history of human lung aging.

    • Seoyeon Lee
    • , Mohammad Naimul Islam
    •  & Mallar Bhattacharya

  • Article
    | Open Access

    Metabolites play an important role in physiology, yet the complexity of the metabolome and its interaction with disease and aging is poorly understood. Here the authors present a comprehensive atlas of the mouse brain metabolome and how it changes during aging.

    • Jun Ding
    • , Jian Ji
    •  & Oliver Fiehn

  • Article
    | Open Access

    Although the first dissection of the human ovary dates back to the 17th century, its characterization is still limited. Here, the authors have unraveled a unique biophysical and topological phenotype of reproductive-age tissue, bridging biophysics and female fertility and providing a blueprint for the artificial ovary.

    • Emna Ouni
    • , Alexis Peaucelle
    •  & Christiani A. Amorim

  • Article
    | Open Access

    The membrane lipids change with ageing and function as regulatory molecules, but the underlying mechanisms are incompletely understood. Here, the authors identify C22 glucosylceramide as a regulator of the longevity transcription factor SKN-1, and show that C22 glucosylceramide regulates lifespan by controlling lysosome homeostasis and subsequent TOR activation.

    • Feng Wang
    • , Yuxi Dai
    •  & Shanshan Pang

  • Article
    | Open Access

    Reactive oxygen species are required for the long lifespan, and glutathione is an antioxidant. Here the authors show that limiting the consumption of dietary thiols, including those naturally derived from the microbiota, increases proteotoxic stress resistance in worms and human cells, and extends C. elegans lifespan.

    • Ivan Gusarov
    • , Ilya Shamovsky
    •  & Evgeny Nudler

  • Article
    | Open Access

    The ‘invariant rate of ageing’ hypothesis suggests that the rate of ageing tends to be constant within species. Here, Colchero et al. find support for the hypothesis across primates, including humans, suggesting biological constraints on the rate of ageing.

    • Fernando Colchero
    • , José Manuel Aburto
    •  & Susan C. Alberts

  • Article
    | Open Access

    Aging is associated with increased frailty and disrupted energy homeostasis. Here, the authors show that SIRT6 overexpression extends the lifespan of male and female mice and demonstrate that SIRT6 optimizes energy homeostasis in old age, which delays frailty and preserves healthy aging.

    • A. Roichman
    • , S. Elhanati
    •  & H. Y. Cohen

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