Ageing

  • 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
  • Article
    | Open Access

    Age-associated decline in tissue function has been linked to alterations in adult stem cells, with implications for organ homeostasis and cellular therapy. Here, the authors study the heterogeneity of ageing mouse haematopoietic stem cells (HSCs) and find that the compromised blood cell-forming potential of individual and functionally defined aged HSCs can be reset by reprogramming.

    • Martin Wahlestedt
    • , Eva Erlandsson
    •  & David Bryder
  • Article
    | Open Access

    Disruption of circadian rhythms leads to reduced healthspan, but the mechanisms by which the normal clock protects aging organisms are not known. Here, the authors show that a subset of genes becomes more rhythmically expressed in older flies, and these are enriched for response to oxidative stress.

    • Rachael C. Kuintzle
    • , Eileen S. Chow
    •  & David A Hendrix
  • Article
    | Open Access

    Irreproducibility of biological findings is a major challenge for drug development. Here the authors examine the lifespans of 22 worm strains in three different laboratories and the effects of ten known chemicals to assess reproducibility in the face of variations in genetic background, chemical treatment and lab environment.

    • Mark Lucanic
    • , W. Todd Plummer
    •  & Patrick C. Phillips
  • Article
    | Open Access

    Mild heat stress has beneficial effects on organismal health and survival. Here, Kumstaet al. show that a mild heat shock and HSF-1 overexpression induce autophagy in multiple tissues of C. elegansand autophagy-related genes are essential for both heat shock-induced and HSF-1–mediated stress resistance and longevity.

    • Caroline Kumsta
    • , Jessica T. Chang
    •  & Malene Hansen
  • Article
    | Open Access

    Probiotic bacteria can improve host health, but the mechanisms underlying such beneficial effects are often unclear. Here, the authors show that biofilm formation of the probiotic bacteriumB. subtilis extends the lifespan of its host, the nematode C. elegans, by reducing insulin-like signalling.

    • Verónica Donato
    • , Facundo Rodríguez Ayala
    •  & Roberto Grau
  • Article
    | Open Access

    Caloric restriction (CR) delays ageing of model organisms, but whether it works in nonhuman primates has been controversial. Here, the authors pool and reanalyse data from two long-running CR primate studies, concluding that moderate CR indeed improves health and survival of rhesus monkeys.

    • Julie A. Mattison
    • , Ricki J. Colman
    •  & Rozalyn M. Anderson
  • Article
    | Open Access

    Part of understanding ageing involves knowing how the brain’s connecting pathways change in healthy aging. Here, authors provide a detailed characterisation of data from 3513 UK Biobank participants, and show that the microstructure of these pathways becomes more similar with age.

    • Simon R. Cox
    • , Stuart J. Ritchie
    •  & Ian J. Deary
  • Article
    | Open Access

    Formation of new blood vessels and bone is coupled. Here the authors show that blood flow represents a key regulator of angiogenesis and endothelial Notch signalling in the bone, and that reactivation of Notch signalling in the endothelium of aged mice rejuvenates the bone.

    • Saravana K. Ramasamy
    • , Anjali P. Kusumbe
    •  & Ralf H. Adams
  • Article
    | Open Access

    Pluripotent stem cells are thought to require a highly active proteostatic machinery. Here, the authors show that CCT8, a subunit of the proteostatic chaperonin complex, is increased in pluripotent stem cells, and that overexpression of CCT8 in worms increases cellular proteostasis and organismal longevity.

    • Alireza Noormohammadi
    • , Amirabbas Khodakarami
    •  & David Vilchez
  • Article
    | Open Access

    Joining the circulatory system of an old with a young animal has been shown to rejuvenate old tissues. Here the authors describe a comparatively simple blood infusion system that allows for the controlled exchange of blood between two animals, and study the effects of a single exchange on various tissues.

    • Justin Rebo
    • , Melod Mehdipour
    •  & Irina M. Conboy
  • Article
    | Open Access

    Since the birth of the first cloned animal, Dolly the sheep, concerns have been raised about potential long-term health consequences of cloning. Here the authors report on a cohort of 13 aged cloned sheep, including four created from the same cells as Dolly, and find they are healthy and seem to age normally.

    • K. D. Sinclair
    • , S. A. Corr
    •  & D. S. Gardner
  • Article
    | Open Access

    Future dramatic rises in dementia are widely reported, assuming no change in incidence. Matthews and colleagues report that, in contrast to such statements, age-specific incidence has dropped over 20 years, with overall incidence of dementia remaining stable in a large multi-site population study from England.

    • F. E. Matthews
    • , B. C. M. Stephan
    •  & G. Forster
  • Article
    | Open Access

    Aging is associated with impaired pancreatic islet function, increased risk of type 2 diabetes, and changes in DNA methylation. Here the authors find blood-based biomarkers that reflect age-associated DNA methylation changes in human pancreatic islets associated with insulin secretion and diabetes.

    • Karl Bacos
    • , Linn Gillberg
    •  & Charlotte Ling
  • Article
    | Open Access

    Understanding the genetic influences on human aging requires a large number of subjects for a study of sufficient power. Here, Jim Wilson and colleagues use information on parental ages at death to show that common variants near the genes for apolipoprotein E and nicotinic acetylcholine receptor subunit alpha 5 are associated with longer lifespan.

    • Peter K. Joshi
    • , Krista Fischer
    •  & James F. Wilson
  • Article
    | Open Access

    The enzyme G6PD generates the reductive metabolite NADPH, which has antioxidant effects, but has also been linked to tumour growth. Here the authors generate mice that modestly overexpress G6PD and report increased lifespan in females, and no negative effects on tumour formation in various genetic models.

    • Sandrina Nóbrega-Pereira
    • , Pablo J. Fernandez-Marcos
    •  & Manuel Serrano
  • Article
    | Open Access

    Mitochondria are asymmetrically inherited during cell division, a process that can affect cell fate and lifespan. Here the authors describe a mechanism for mitochondrial quality control in yeast that maintains a reservoir of high-functioning mitochondria in mother cells and preserves maternal reproductive capacity.

    • Wolfgang M. Pernice
    • , Jason D. Vevea
    •  & Liza A. Pon
  • Article
    | Open Access

    The study of germline mutations has been greatly enhanced by massive parallel sequencing technologies. Here the authors use deep sequencing data from nearly 700 parent-child trios to show maternal age has a small but significant correlation with the number of de novomutations in the offspring.

    • Wendy S. W. Wong
    • , Benjamin D. Solomon
    •  & John E. Niederhuber
  • Article
    | Open Access

    Organismal ageing is driven by conserved biological processes. Here the authors build on a comparative RNA-seq analysis in three model organisms to demonstrate that the gene, bcat-1, which catalyses the degradation of branched-chain amino acids, regulates lifespan in worms.

    • Johannes Mansfeld
    • , Nadine Urban
    •  & Michael Ristow
  • Article
    | Open Access

    The aging myopathy is characterized by diastolic dysfunction of unknown aetiology. Rota et al. show that increased late Na+ current (INaL) underlies diastolic dysfunction in the aged heart, and that inhibiting INaLimproves diastolic indices and corrects the kinetics of cardiomyocyte contraction and relaxation in aged mice.

    • Sergio Signore
    • , Andrea Sorrentino
    •  & Marcello Rota
  • Article
    | Open Access

    TheC. elegans nervous system influences organismal lifespan but mechanistic details are poorly understood. Here, Chun et al. show that the neurotransmitter GABA regulates worm lifespan by acting on GABABreceptors in motor neurons, which activate the transcription factor DAF-16 in the intestine.

    • Lei Chun
    • , Jianke Gong
    •  & Jianfeng Liu
  • Article
    | Open Access

    Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.

    • Marjolein J. Peters
    • , Roby Joehanes
    •  & Andrew D. Johnson
  • Article
    | Open Access

    The capacity for thermoregulation deteriorates with age, particularly in cold environments. Here the authors demonstrate inDrosophilathat age-related changes in cold avoidance result from a shift in the relative contribution of two parallel mushroom body circuits that are modulated by dopamine.

    • Hsiang-Wen Shih
    • , Chia-Lin Wu
    •  & Ann-Shyn Chiang
  • Article
    | Open Access

    As oocytes age the frequency of chromosome segregation errors during meiosis I increases. Here the authors use live imaging of oocytes from naturally aged mice to provide direct evidence that bivalent separation into univalents is the primary defect responsible for age-related aneuploidy.

    • Yogo Sakakibara
    • , Shu Hashimoto
    •  & Tomoya S. Kitajima
  • Article
    | Open Access

    We currently lack a detailed understanding of the neurobiological basis for the decline of male sexual desire with age. Here the authors demonstrate that restoring impaired dopaminergic signalling in a specific cluster of neurons in the Drosophilabrain increases sexual behaviour in ageing male flies.

    • Shu-Yun Kuo
    • , Chia-Lin Wu
    •  & Tsai-Feng Fu
  • Article
    | Open Access

    The protein p16INK4a promotes senescence in tissue stem cells and thereby contributes to organismal ageing. Here the authors reveal that p16INK4a also downregulates expression of a-klotho, thereby revealing an additional ageing-promoting function of 16INK4athat is independent from its role in senescence.

    • Seidai Sato
    • , Yuka Kawamata
    •  & Eiji Hara
  • Article |

    Aging leads to impaired differentiation and increased pool size of hematopoietic stem cells (HSCs). Here, the authors show that wild-type p53-induced phosphatase 1 (Wip1), a negative regulator of DNA damage response pathways, regulates aging-associated HSC differentiation and expansion viap53 and mTORC1 pathways, respectively.

    • Zhiyang Chen
    • , Weiwei Yi
    •  & Zhenyu Ju
  • Article
    | Open Access

    Sperm from aging males may decline in quality, but it is unclear how aging affects the ability of males to produce successful offspring. Here, the authors show that paternal aging of captive long-lived houbara bustards reduces both the likelihood that eggs hatch and the rate at which chicks grow.

    • Brian T. Preston
    • , Michel Saint Jalme
    •  & Gabriele Sorci
  • Review Article |

    Proteins are subject to continuous and complex quality-control mechanisms, which ensure integrity of the proteome. Vilchez et al.review how a demise in these processes, collectively referred to as proteostasis, is linked to organismal ageing and the development of age-associated diseases.

    • David Vilchez
    • , Isabel Saez
    •  & Andrew Dillin
  • Article |

    Aspects of visual perception learning are known to change with age, but the associated structural correlates are poorly understood. Here the authors show that, surprisingly, visual perception in older individuals involves training-induced structural changes in white matter that are absent in younger individuals.

    • Yuko Yotsumoto
    • , Li-Hung Chang
    •  & Yuka Sasaki