Ageing

  • 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
  • Article
    | Open Access

    Natural selection may favor traits underlying aging-related diseases if they benefit the young. Wang et al. find that oxidative activation of CaMKII provides physiological benefits critical to the initial and continued success of vertebrates but at the cost of disease, frailty, and shortened lifespan.

    • Qinchuan Wang
    • , Erick O. Hernández-Ochoa
    •  & Mark E. Anderson
  • Article
    | Open Access

    Short term systemic expression of the reprogramming factors Oct-3/4, Sox2, Klf4, c-Myc (OSKM) rejuvenates aging cells and promotes tissue regeneration. Here the authors show that myofiber-specific expression of OSKM accelerates muscle regeneration by reducing secretion of muscle stem cell quiescence promoting Wnt4.

    • Chao Wang
    • , Ruben Rabadan Ros
    •  & Juan Carlos Izpisua Belmonte
  • Review Article
    | Open Access

    Circadian clocks link physiologic processes to environmental conditions and a mismatch between internal and external rhythms has negative effects on organismal health. In this review, the authors discuss the interactions between circadian clocks and dietary interventions targeted to promote healthy aging.

    • Victoria A. Acosta-Rodríguez
    • , Filipa Rijo-Ferreira
    •  & Joseph S. Takahashi
  • Article
    | Open Access

    Histone acetylations are important epigenetic marks for transcriptional activation and respond to metabolic changes. Here the authors develop a lifespan screen and show that inactivation of the histone deacetylase complex activates longevity and protects against stress via trehalose metabolism.

    • Ruofan Yu
    • , Xiaohua Cao
    •  & Weiwei Dang
  • Article
    | Open Access

    ASXL1 mutations are frequently found in age-related clonal haemaotopoiesis (CH), but how they drive CH is unclear. Here the authors show that expression of C-terminal truncated ASXL1 in haematopoietic stem cells (HSCs) leads to Akt de-ubiquitination, activated Akt/mTOR signaling, and aberrant HSC proliferation.

    • Takeshi Fujino
    • , Susumu Goyama
    •  & Toshio Kitamura
  • Article
    | Open Access

    Dietary restriction (DR) can increase protein persulfidation but the tissue specificity of this process is not well understood. Here, the authors compare organ-specific protein persulfidomes in young and aged mice under DR, and show that DR-dependent persulfidome changes depend on cystathionine γ-lyase.

    • Nazmin Bithi
    • , Christopher Link
    •  & Christopher Hine
  • Article
    | Open Access

    Sensory perception and metabolic homeostasis are known to deteriorate with ageing, while mechanisms underlying their deterioration remain poorly understood. Here, the authors demonstrate that decrease of intraflagellar transport in the cilia of sensory neurons impairs sensory perception and metabolism in ageing C. elegans.

    • Yincong Zhang
    • , Xiaona Zhang
    •  & Yidong Shen
  • Article
    | Open Access

    Aging is associated with declining protein homeostasis. Here, using a chemical mutagenesis screen for lifespan extension in C. elegans, the authors report that inhibition of the integrated stress response enhances longevity and protein homeostasis in a manner dependent on kin-35, without reducing protein synthesis.

    • Maxime J. Derisbourg
    • , Laura E. Wester
    •  & Martin S. Denzel
  • Article
    | Open Access

    Sarcopenia is the age-associated functional decline and atrophy of muscle fibers, and it has been proposed that it might be counteracted by inducing myofiber hypertrophy. Here, the authors show that expression levels of the ubiquitin ligase UBR4 are increased with ageing, and that whilst its genetic ablation rescues muscle atrophy, it is also associated with reduced protein quality and impaired force production in Drosophila and mouse models.

    • Liam C. Hunt
    • , Bronwen Schadeberg
    •  & Fabio Demontis
  • Article
    | Open Access

    The regeneration of functional tendons remains a clinical challenge. Here the authors develop a biomimetic scaffold loaded with recombinant periostin and demonstrate its functionality in promoting tendon stem/progenitor cell recruitment and tenogenic differentiation, and tendon regeneration in a rat full-cut Achilles tendon defect model.

    • Yu Wang
    • , Shanshan Jin
    •  & Yan Liu
  • Article
    | Open Access

    Muscle atrophy is associated with ageing, but the underlying molecular mechanisms are not well understood. Here, they authors show that ablation of the E3 ubiquitin ligase Mib1 is important for myofibre maintenance via a mechanism that involves targeting and degradation of Actn3, and that Mib1 ablation in mice induces muscle atrophy which can be rescued by knockown of Actn3 expression.

    • Ji-Yun Seo
    • , Jong-Seol Kang
    •  & Young-Yun Kong
  • Article
    | Open Access

    Haematopoietic stem cells (HSCs) are characterized by their self-renewal potential and associated dormancy. Here the authors show that niche produced netrin-1 preserves HSC quiescence and self-renewal via neogenin-1, and that decline of netrin-1 production during ageing leads to decreased Neo1 mediated HSC self-renewal.

    • Simon Renders
    • , Arthur Flohr Svendsen
    •  & Andreas Trumpp
  • Review Article
    | Open Access

    Loss of muscle mass is associated with ageing and with a number of diseases such as cancer. Here, the authors review the signaling pathways that modulate protein synthesis and degradation and gain or loss of muscle mass, and discuss therapeutic implications and future directions for the field.

    • Roberta Sartori
    • , Vanina Romanello
    •  & Marco Sandri
  • Article
    | Open Access

    The discovery of interventions that slow aging could be accelerated by employing non-invasive biometrics that predict biological age or life expectancy. Here the authors use longitudinal frailty data from naturally aging mice to develop two such tools, that are responsive to interventions.

    • Michael B. Schultz
    • , Alice E. Kane
    •  & David A. Sinclair
  • Article
    | Open Access

    mTORC1 expression is increased during ageing of muscle, and on the other hand, its activation promotes muscle hypertrophy. Here, the authors assess whether mTORC1 has positive or negative effects on ageing, and show that its long-term inhibition preserves muscle mass and function and neuromuscular junction integrity, whereas muscle-specific activation is associated with sarcopenia.

    • Daniel J. Ham
    • , Anastasiya Börsch
    •  & Markus A. Rüegg
  • Article
    | Open Access

    Phosphatidylinositol 3-kinase catalyzes the reaction from PI(4,5)P2 to PI(3,4,5)P3 and is encoded by the age-1 gene known to regulate lifespan. Here the researchers found that the metabolite myo-inositol, which can be converted to PI(3,4,5)P3 extends worm lifespan and alleviates worm as well as mouse health decline during aging.

    • Dawei Shi
    • , Xian Xia
    •  & Jing-Dong J. Han
  • Article
    | Open Access

    Blood–brain barrier dysfunction occurs in ageing and in neurodegenerative diseases. Here, the authors use scRNA-seq to identify transcriptomic changes in endothelial cell subtypes in the aged mouse brain, some of which may generalize to human and can be reversed by treatment with a GLP-1R agonist.

    • Lei Zhao
    • , Zhongqi Li
    •  & Ho Ko
  • Article
    | Open Access

    Organ transplantation involving aged donors is often confounded by reduced post-transplantation organ survival. By studying both human organs and mouse transplantation models, here the authors show that pretreating the donors with senolytics to reduce mitochondria DNA and pro-inflammatory dendritic cells may help promote survival of aged organs.

    • Jasper Iske
    • , Midas Seyda
    •  & Stefan G. Tullius
  • Article
    | Open Access

    Chronic inflammation is a feature of age-related regenerative decline in skeletal muscles, but how it directly affects resident muscle stem cell fate and function is unclear. Here, the authors show that Ccr2 signaling in muscle stem cell derived progenitors represses terminal myogenic differentiation, and that targeting Ccr2 on aged myogenic progenitors rejuvenates aged skeletal muscle healing and function.

    • Roméo S. Blanc
    • , Jacob G. Kallenbach
    •  & Joe V. Chakkalakal
  • Article
    | Open Access

    Autophagic activity declines with age in several tissues and is linked to aging-associated functional decline and pathologies. Here the authors show that Rubicon, a negative regulator of autophagy, decreases in adipocytes with age, and its loss leads to adipocyte dysfunction via excess autophagic degradation of SRC-1 and TIF2.

    • Tadashi Yamamuro
    • , Tsuyoshi Kawabata
    •  & Tamotsu Yoshimori
  • Article
    | Open Access

    Supercentenarians are approaching the current longevity limit by avoiding or surviving major illness, thus identifying biomarkers for exceptional survival might provide insights into the protection against disease of aging. Here, the authors show low NT-proBNP and high albumin in plasma are the biological correlates of survival to the highest ages.

    • Takumi Hirata
    • , Yasumichi Arai
    •  & Nobuyoshi Hirose
  • Article
    | Open Access

    Ageing phenotypes are of great interest but are difficult to study genetically, partly due to the sample sizes required. Here, the authors present a multivariate framework to combine GWAS summary statistics and increase statistical power, identifying additional loci enriched for aging.

    • Paul R. H. J. Timmers
    • , James F. Wilson
    •  & Joris Deelen
  • Article
    | Open Access

    Aging is the major risk factor for cardiovascular diseases due to chronic, low-grade inflammation stemmed from pro-inflammatory factors circulating in the body. Here, the authors identify a role of hepatocyte specific peroxisomal import in mediating non-autonomous regulation of cardiac aging, through upregulation of IL6-like inflammatory cytokine.

    • Kerui Huang
    • , Ting Miao
    •  & Hua Bai
  • Article
    | Open Access

    Naked mole rats are the longest-lived rodents and produce very-high-molecular-mass hyaluronan (vHMM-HA). Here the authors show that naked mole rat vHMM-HA is better at protecting mouse and human cells from cell cycle arrest and cell death, compared to the high-molecular-mass hyaluronan produced by these species.

    • Masaki Takasugi
    • , Denis Firsanov
    •  & Vera Gorbunova
  • Article
    | Open Access

    Arterial degeneration, closely associated with cardiovascular diseases, is driven by aging-related vascular cell-specific transcriptomics changes. This study provides a single-cell transcriptomic atlas for senile aortic and coronary arteries and underscores FOXO3A-based the transcriptional network in vasoprotection during aging.

    • Weiqi Zhang
    • , Shu Zhang
    •  & Jing Qu
  • Article
    | Open Access

    Disruption of different components of molecular circadian clocks has varying effects on health and lifespan of model organisms. Here the authors show that loss of period extends life in drosophila melanogaster.

    • Matt Ulgherait
    • , Anna Chen
    •  & Mimi Shirasu-Hiza
  • Article
    | Open Access

    Aging involves gradual loss of tissue function, and transcription factor (TF) expression can ameliorate this in progeroid mice. Here the authors show that transient TF expression reverses age-associated epigenetic marks, inflammatory profiles and restores regenerative potential in naturally aged human cells.

    • Tapash Jay Sarkar
    • , Marco Quarta
    •  & Vittorio Sebastiano
  • Article
    | Open Access

    Whether the immune system aging differs between men and women is barely known. Here the authors characterize gene expression, chromatin state and immune subset composition in the blood of healthy humans 22 to 93 years of age, uncovering shared as well as sex-unique alterations, and create a web resource to interactively explore the data.

    • Eladio J. Márquez
    • , Cheng-han Chung
    •  & Duygu Ucar
  • Article
    | Open Access

    Mutations in the hexosamine pathway key enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) improve protein quality control and extend C. elegans lifespan. Here the authors present the crystal structures of full-length human GFAT-1 alone and with bound ligands and perform activity assays, which show that gain-of-function in the longevity-associated G451E variant is caused by a loss of feedback regulation.

    • Sabine Ruegenberg
    • , Moritz Horn
    •  & Martin S. Denzel
  • Article
    | Open Access

    Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.

    • Mark Pinese
    • , Paul Lacaze
    •  & David M. Thomas
  • Article
    | Open Access

    The transcription factor DAF-16/FOXO mediates a wide variety of aging-preventive responses by driving the expression of stress resistance and longevity promoting genes. Here the authors show that transcriptional initiation at many DAF-16/FOXO target genes requires the dephosphorylation of SPT-5 by Protein Phosphatase 4.

    • Ilke Sen
    • , Xin Zhou
    •  & Christian G. Riedel
  • Article
    | Open Access

    Intestinal aging is associated with declines in structure and absorption of nutrients. Here, the authors show that aging related intestinal decline is mediated by activation of the mTORC1-p38MAPK-p53 pathway in intestinal stem cells and can be ameliorated by abrogating mTORC1 or p38MAPK activity.

    • Dan He
    • , Hongguang Wu
    •  & Baojie Li
  • Article
    | Open Access

    Sarcopenia is the loss of muscle mass and strength associated with physical disability during ageing. Here, the authors analyse muscle biopsies from 119 patients with sarcopenia and age-matched controls of different ethnic groups and find transcriptional signatures indicating mitochondrial dysfunction, associated with reduced mitochondria numbers and lower NAD+ levels in older individuals with sarcopenia.

    • Eugenia Migliavacca
    • , Stacey K. H. Tay
    •  & Jerome N. Feige