Edited by
Matt Kaeberlein et al.

Aging, Geroscience and Longevity: A Special Issue

eLife is pleased to present a Special Issue to highlight recent advances in the mechanistic understanding of aging and interventions that extend longevity.
Collection
  • Views 6,299

Breakthroughs in aging-related research are revealing details of how cellular processes and tissue functions decline during aging and have pinpointed longevity factors conserved among eukaryotes. In parallel, investigations in model organisms are uncovering potential approaches to extend lifespan in humans.

To highlight recent advances in the mechanistic understanding of aging and interventions that extend longevity, eLife is pleased to present a Special Issue devoted to this exciting topic. This issue presents a collection of highly influential research selected for publication by a specially convened group of experts.

To support the launch of the issue, Senior Editors Jessica Tyler and Matt Kaeberlain explore a new era for research into aging in their Editorial.

Collection

    1. Epidemiology and Global Health

    Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up

    Xia Li et al.
    Biological ages have the potential to provide aging-related information beyond chronological age and can be predictive of mortality independently of both chronological age and different types of biological ages.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    Pan-mammalian analysis of molecular constraints underlying extended lifespan

    Amanda Kowalczyk et al.
    Cancer control, DNA repair, and immunity are key functionalities underlying the evolution of extended lifespan in mammals.
    1. Genetics and Genomics

    Germline burden of rare damaging variants negatively affects human healthspan and lifespan

    Anastasia V Shindyapina et al.
    Rare highly damaging mutations that are present in most human genomes decrease lifespan and are associated with an earlier onset of chronic diseases.
    1. Cell Biology
    2. Immunology and Inflammation

    Rapamycin rejuvenates oral health in aging mice

    Jonathan Y An et al.
    Short-term treatment with rapamycin reverses periodontal bone loss, attenuates inflammation, and remodels the oral microbiome toward a more youthful state.
    1. Epidemiology and Global Health

    Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm

    Daniel W Belsky et al.
    Methylation pace of aging is a novel measure requiring only a blood sample that clinical-trial and observational studies can use to test if treatments modify how fast participants are aging.
    1. Genetics and Genomics

    mRNA decapping is an evolutionarily conserved modulator of neuroendocrine signaling that controls development and ageing

    Fivos Borbolis et al.
    mRNA decapping function in neuronal cells regulates neurosecretion and intertissue signaling, affecting developmental and ageing processes in two model organisms.
    1. Cell Biology
    2. Stem Cells and Regenerative Medicine

    Opposing p53 and mTOR/AKT promote an in vivo switch from apoptosis to senescence upon telomere shortening in zebrafish

    Mounir El Maï et al.
    Telomere shortening with age promotes a switch from p53-dependent apoptosis to senescence prompted by tissue damage that triggers conflicting mTOR/AKT signalling, lower OxPhos defences and ROS, mitochondria dysfunction and senescence.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Translational control of one-carbon metabolism underpins ribosomal protein phenotypes in cell division and longevity

    Nairita Maitra et al.
    Extensive molecular profiling shows how loss of highly similar, paralogous ribosomal proteins lead to distinct phenotypic outputs, through translational control of specific mRNAs.
    1. Medicine

    Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice

    Ying Ann Chiao et al.
    Mitochondrial-targeted SS-31 peptide ameliorates mitochondrial dysfunction and rescues pre-existing cardiac dysfunction in old mice, supporting the translational potential of mitochondrial protective interventions to treat age-related diseases.
    1. Genetics and Genomics

    Ovariectomy uncouples lifespan from metabolic health and reveals a sex-hormone-dependent role of hepatic mTORC2 in aging

    Sebastian I Arriola Apelo et al.
    Metabolic health and longevity can be separated by ovariectomy, which also protects female mice lacking hepatic mTORC2 from midlife mortality.
    1. Biochemistry and Chemical Biology

    Changes in ferrous iron and glutathione promote ferroptosis and frailty in aging Caenorhabditis elegans

    Nicole L Jenkins et al.
    As worms age reduced glutathione together with increased ferrous iron increases frailty and leads to ferroptosis, which is amenable to therapeutic intervention.
    1. Cell Biology
    2. Medicine

    Senotherapeutic drugs for human intervertebral disc degeneration and low back pain

    Hosni Cherif et al.
    Targeting senescent cells in human intervertebral discs, using senotherapeutics, provides a potential therapeutic strategy to prevent or reduce disc degeneration and pain.
    1. Evolutionary Biology
    2. Genetics and Genomics

    Intra-species differences in population size shape life history and genome evolution

    David Willemsen et al.
    Population genetics in turquoise killifish wild populations reveals how small population size and genetic drift determine the accumulation of deleterious gene variants leading to short lifespan.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin

    Morgan Levine et al.
    The first epigenetic clock for rats was developed and revealed to reflect phenotypic aging and captured the effects of longevity interventions.
    1. Cancer Biology
    2. Immunology and Inflammation

    The effects of age and systemic metabolism on anti-tumor T cell responses

    Jefte M Drijvers et al.
    A comprehensive literature review delineates the current knowledge of how systemic context, such as age and obesity, can impact CD8+ T cell function, anti-tumor immunity, and immunotherapy responsiveness.
    1. Cell Biology

    Polo-like kinase acts as a molecular timer that safeguards the asymmetric fate of spindle microtubule-organizing centers

    Laura Matellán et al.
    Molecular and cell biology analyses reveal novel roles of Polo-like kinases in establishing non-random segregation patterns of spindle-associated microtubule-organizing centers during mitosis, a phenomenon linked with replicative cell aging.
    1. Cell Biology

    Casein kinase 1G2 suppresses necroptosis-promoted testis aging by inhibiting receptor-interacting kinase 3

    Dianrong Li et al.
    Casein kinase 1G2 interacts with and inhibits the activation of receptor-interacting kinase 3, RIP3, in response to TNF and toll-like receptor family members and attenuates its necroptosis signaling activity.
    1. Neuroscience

    Small molecule cognitive enhancer reverses age-related memory decline in mice

    Karen Krukowski et al.
    Inhibition of the integrated stress response restores neuronal and immune dysfunction and alleviates memory deficits in aged mice.
    1. Immunology and Inflammation

    Autophagy in T cells from aged donors is maintained by spermidine and correlates with function and vaccine responses

    Ghada Alsaleh et al.
    Declining TFEB and autophagy levels with age are key to poor vaccination efficacy in the elderly.
    1. Genetics and Genomics

    Downregulation of the tyrosine degradation pathway extends Drosophila lifespan

    Andrey A Parkhitko et al.
    The tyrosine degradation pathway reprogramming connects mitochondrial dysfunction, aging, and production of tyrosine-derived neuromediators that can be targeted with an FDA-approved drug, Tigecycline.
    1. Cell Biology

    Reduction of elevated proton leak rejuvenates mitochondria in the aged cardiomyocyte

    Huiliang Zhang et al.
    The primary respiratory defect seen in aged cardiomyocytes is an elevated proton leak mediated by ANT1, and this is prevented by treatment with SS-31 (elamipretide).
    1. Genetics and Genomics
    2. Neuroscience

    Cell non-autonomous regulation of health and longevity

    Hillary A Miller et al.
    Modulation of the aging process through cell signaling represents a recent and exciting area of study with the potential for development of therapeutics to extend human health.
    1. Developmental Biology

    Optogenetic control of gut bacterial metabolism to promote longevity

    Lucas A Hartsough et al.
    Light controls can fine tune microbiome–host interaction to qualitatively regulate host longevity with temporal and spatial precision.
    1. Medicine

    Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α

    Shivani N Mann et al.
    17α-Estradiol, a life-span extending compound, signals through estrogen receptor α (ERα) in the liver and hypothalamus to elicit health benefits in a sex-specific manner.
    1. Evolutionary Biology
    2. Medicine

    A dietary sterol trade-off determines lifespan responses to dietary restriction in Drosophila melanogaster females

    Brooke Zanco et al.
    Micronutrients, not macronutrients, regulate lifespan.
    1. Genetics and Genomics

    Drosophila serotonin 2A receptor signaling coordinates central metabolic processes to modulate aging in response to nutrient choice

    Yang Lyu et al.
    Dietary choice per se is sufficient to modulate aging in Drosophila and through serotonergic control of peripheral metabolism.
    1. Cell Biology
    2. Medicine

    Research: A new era for research into aging

    Matt Kaeberlein, Jessica K Tyler
    eLife is publishing a special issue on aging, geroscience and longevity to mark the rapid progress made in this field over the past decade, both in terms of mechanistic understanding and translational approaches that are poised to have clinical impact on age-related diseases.
    Editorial
    Available as:
    • HTML
    • PDF
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    A physicochemical perspective of aging from single-cell analysis of pH, macromolecular and organellar crowding in yeast

    Sara N Mouton et al.
    In mitotically aging yeast cells, the cytosol acidifies, the distances between the organellar membranes decrease dramatically, but crowding on the scale of the average size protein is relatively stable.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Cytoplasmic chromatin fragments—from mechanisms to therapeutic potential

    Karl N Miller et al.
    Cytoplasmic chromatin fragment formation pathways in senescent cells are a potential therapeutic target for modulation of inflammation in aging, which contributes to age-associated diseases.
    1. Cell Biology
    2. Developmental Biology

    A Non-stop identity complex (NIC) supervises enterocyte identity and protects from premature aging

    Neta Erez et al.
    A nuclear Non-stop identity complex (NIC) supervises enterocyte (EC) identity, preserves tissue homeostasis, and prevents premature aging by maintaining EC-specific gene expression, silencing non-relevant programs, and safeguarding large-scale nuclear organization.
    1. Chromosomes and Gene Expression
    2. Medicine

    Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells

    Karthik Amudhala Hemanthakumar et al.
    Endothelial dysfunction due to cardiovascular disease risk factors explained by cardiac endothelial cell transcriptome remodelling.
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology

    Increased longevity due to sexual activity in mole-rats is associated with transcriptional changes in the HPA stress axis

    Arne Sahm et al.
    The fact that sexual activity/reproduction doubles the lifespan of certain rodent species is most likely linked to critical changes in the regulation of the hypothalamic–pituitary–adrenal stress axis.
    1. Genetics and Genomics

    Age-related changes in polycomb gene regulation disrupt lineage fidelity in intestinal stem cells

    Helen M Tauc et al.
    Global, multi-angled genetic analyses identified an age-associated loss of stem cell lineage fidelity that was linked to changes in polycomb regulation in the Drosophila intestinal epithelium.
    1. Computational and Systems Biology

    Proteomic and transcriptomic profiling reveal different aspects of aging in the kidney

    Yuka Takemon et al.
    mRNA profiling alone provides an incomplete picture of molecular aging and examination of changes in proteins is essential to understand aging processes that are not transcriptionally regulated.
    1. Computational and Systems Biology

    Mouse aging cell atlas analysis reveals global and cell type-specific aging signatures

    Martin Jinye Zhang et al.
    Comprehensive single-cell transcriptome analysis reveals global and tissue-specific aging markers and characterizes the heterogeneous aging status of different cell types and tissues in mouse.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    Selenium supplementation inhibits IGF-1 signaling and confers methionine restriction-like healthspan benefits to mice

    Jason D Plummer et al.
    Dietary selenium supplementation confers to mice all of the short-term healthspan benefits of the longevity-promoting intervention methionine restriction, and thus may represent a method to promote healthy aging in mammals.
    1. Cell Biology

    A genetic screen identifies new steps in oocyte maturation that enhance proteostasis in the immortal germ lineage

    Madhuja Samaddar et al.
    A whole-genome genetic screen links new aspects of oocyte maturation to proteostasis renewal in the immortal Caenorhabditis elegans germ-cell lineage and reveals similarities to somatic cell maintenance during aging.
    1. Genetics and Genomics
    2. Neuroscience

    Integrated transcriptomic and neuroimaging brain model decodes biological mechanisms in aging and Alzheimer’s disease

    Quadri Adewale et al.
    Identification of causal genes and their effects on other biological determinants untangles the complexities of aging and Alzheimer's and can facilitate drug discovery for sustaining healthy aging and treating Alzheimer's.
    1. Genetics and Genomics

    Whole-genome sequencing analysis of semi-supercentenarians

    Paolo Garagnani et al.
    Genetic variants located in DNA repair genes and a reduced burden of somatic mutations protect the oldest living persons from age-related diseases, allowing an healthy aging phenotype.
    1. Computational and Systems Biology
    2. Stem Cells and Regenerative Medicine

    The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function

    Zachary Clemens et al.
    Transcriptomic analysis using a novel information-based network entropy approach provides mechanistic insights into the ability of Klotho to successfully ameliorate age-related sarcopenia in old mice, but not oldest-old mice.
    1. Computational and Systems Biology

    A cross-sectional study of functional and metabolic changes during aging through the lifespan in male mice

    Michael A Petr et al.
    A comprehensive cross-sectional assessment reveals functional decline in mice consistent with increased energetic cost of physical activity with age through metabolic rewiring in multiple organs.
    1. Epidemiology and Global Health

    Sex differences in biological aging with a focus on human studies

    Sara Hägg, Juulia Jylhävä
    Biological aging processes and age-related diseases demonstrate sexual dimorphism where complex interactions between underlying aging mechanisms and sex chromosomes and hormones are seen in humans and animals.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing

    Yu-Xuan Lu et al.
    Modulation of histone levels in gut enterocytes by rapamycin treatment alters chromatin organisation and induces intestinal autophagy through transcriptional regulation to prevent age-related decline in the intestine and extend lifespan.
    1. Immunology and Inflammation

    NHR-49/PPAR-α and HLH-30/TFEB cooperate for C. elegans host defense via a flavin-containing monooxygenase

    Khursheed A Wani et al.
    Genetic and molecular characterization showed that evolutionarily conserved flavin-containing monooxygenase (FMO-2) plays an important role in host defense in Caenorhabditis elegans, and its induction is dependent on conserved transcription factors, TFEB and PPAR-α.
    1. Cell Biology

    The mitochondrial permeability transition pore activates the mitochondrial unfolded protein response and promotes aging

    Suzanne Angeli et al.
    Loss of the F-ATP synthase c-subunit inhibits a pathological mitochondrial permeability transition pore that is coupled to a maladaptive mitochondrial unfolded protein response while also extending lifespan.

Contributors

  1. Matt Kaeberlein
    Senior Editor
  2. Jessica Tyler
    Senior Editor
  3. Weiwei Dang
    Reviewing Editor
  4. Yousin Suh
    Guest Editor
  5. Dario Riccardo Valenzano
    Reviewing Editor
  6. Jing-Dong Jackie Han
    Reviewing Editor
  7. Veronica Galvan
    Guest Editor
  8. Pankaj Kapahi
    Reviewing Editor
  9. Jan Gruber
    Reviewing Editor
  10. Sara Hägg
    Reviewing Editor