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
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Epidemiology and Global Health
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.
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Genetics and Genomics
Rare highly damaging mutations that are present in most human genomes decrease lifespan and are associated with an earlier onset of chronic diseases.
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Cell Biology
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Immunology and Inflammation
Short-term treatment with rapamycin reverses periodontal bone loss, attenuates inflammation, and remodels the oral microbiome toward a more youthful state.
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Epidemiology and Global Health
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.
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Genetics and Genomics
mRNA decapping function in neuronal cells regulates neurosecretion and intertissue signaling, affecting developmental and ageing processes in two model organisms.
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Cell Biology
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Stem Cells and Regenerative Medicine
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.
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Medicine
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.
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Genetics and Genomics
Metabolic health and longevity can be separated by ovariectomy, which also protects female mice lacking hepatic mTORC2 from midlife mortality.
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Biochemistry and Chemical Biology
As worms age reduced glutathione together with increased ferrous iron increases frailty and leads to ferroptosis, which is amenable to therapeutic intervention.
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Cell Biology
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Medicine
Targeting senescent cells in human intervertebral discs, using senotherapeutics, provides a potential therapeutic strategy to prevent or reduce disc degeneration and pain.
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Evolutionary Biology
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Genetics and Genomics
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.
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Cancer Biology
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Immunology and Inflammation
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.
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Cell Biology
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.
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Cell Biology
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.
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Neuroscience
Inhibition of the integrated stress response restores neuronal and immune dysfunction and alleviates memory deficits in aged mice.
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Genetics and Genomics
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.
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Cell Biology
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).
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Genetics and Genomics
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Neuroscience
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.
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Developmental Biology
Light controls can fine tune microbiome–host interaction to qualitatively regulate host longevity with temporal and spatial precision.
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Medicine
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.
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Genetics and Genomics
Dietary choice per se is sufficient to modulate aging in Drosophila and through serotonergic control of peripheral metabolism.
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Cell Biology
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Medicine
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.
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Cell Biology
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Chromosomes and Gene Expression
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.
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Cell Biology
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Developmental Biology
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.
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Genetics and Genomics
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.
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Computational and Systems Biology
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.
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Computational and Systems Biology
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.
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Biochemistry and Chemical Biology
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Genetics and Genomics
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.
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Cell Biology
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.
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Genetics and Genomics
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Neuroscience
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.
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Genetics and Genomics
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.
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Computational and Systems Biology
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.
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Epidemiology and Global Health
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.
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Cell Biology
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Chromosomes and Gene Expression
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.
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Immunology and Inflammation
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.
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Genetics and Genomics
Separate genetic pathways mediate longevity, pathogen resistance, and cell-nonautonomous regulation of xenobiotic detoxification in chemosensory defective Caenorhabditis elegans mutants.
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Cell Biology
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.