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ß-adrenergic signalling is implicated in a number of human age-related diseases. Sumit et al show that the activation of ß-adrenergic-like pathway in the female fruit fly gut is sufficient to promote organismal longevity.

Researchers identified a previously unrecognized progeroid neuropathy caused by mutations in IVNS1ABP. Patient-derived fibroblasts, induced pluripotent stem cells, and neural progenitor cells exhibited disrupted dynamics, resulting in defective cytokinesis, DNA damage, and cellular senescence, which in turn led to premature neurogenesis in cerebral organoids.

Hematopoietic stem cell aging manifests in gene expression changes but the overarching regulatory framework behind these changes is lesser known. Here authors perform epigenetic profiling in aged hematopoietic stem cells to find that a changed chromatin looping pattern leads to overexpression of a shorter Btaf1 variant, driving a set of aging-associated genes leading to increased megakaryocyte progenitor cell production.

For calorie-restriction-adapted King penguins, living a sedentary life at the zoo increases life expectancy; but by suppressing metabolic challenges, it also accelerates the epigenetic markers of ageing, decoupling lifespan from health.

In C. elegans, a p38 MAPK–ATF-7 pathway upregulates hypodermal CATP-3 during potassium scarcity, integrating neuronal signals to maintain homeostasis, enhance survival, and link potassium regulation to lifespan and immunity. This conserved mechanism is distinct from osmotic stress responses.

At single-cell resolution, Tarkhov et al. delineate stochastic and co-regulated components of epigenetic aging, revealing a simultaneous loss of regulation at the epigenetic and transcriptional levels in aging.

To dissect lncRNA functions in aging, here the authors perform a CRISPRi-based single-nucleus multiomics screen systematically perturbing 32 aging- and senescence-associated lncRNAs and measuring matched changes in gene expression and chromatin accessibility. They pinpoint a role for HOTAIRM1 linked to DNA repair-related gene control and show that replenishing HOTAIRM1 in mouse lungs reduces fibrosis.

Heterochronic human serum in a microphysiological system of hiPSC-derived white adipose tissue–liver axis allows the study of aging and rejuvenation in humans.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

When senescent cells accumulate during adulthood they negatively influence lifespan and promote age-dependent changes in several organs; clearance of these cells delayed tumorigenesis in mice and attenuated age-related deterioration of several organs without overt side effects, suggesting that the therapeutic removal of senescent cells may be able to extend healthy lifespan.

This PrimeView highlights the signs of male hypogonadism through the lifespan and describes the key underlying causes of the condition in boys and men.

Age-related microbiome changes increase medium-chain fatty acid-producing bacteria, driving GPR84-mediated myeloid inflammation, impaired vagal signalling and hippocampal dysfunction; targeting this gut–brain pathway restores memory in aged mice.

Gallrein et al. pair functional assays with clocks to compare chronological versus biological age of single neuron types in C. elegans, to probe their vulnerability or resilience to neurodegeneration, and use an in silico screen to identify neuroprotective drugs.

The glycolytic metabolite phosphoenolpyruvate (PEP) is identified as a protective factor during aging. Acting as an endogenous inhibitor of cGAS−STING, PEP reduces inflammation and improves cognition in Alzheimer’s disease mice. PEP levels correlate with healthy traits in humans.

Single-cell and spatial transcriptomics shed light on murine ovarian aging, characterized by pro-inflammatory immune cell populations communicating with granulosa cells to drive inflammaging.

Ageing reprograms the evolutionary trajectory of KRAS-driven lung adenocarcinoma, limiting primary tumour growth while promoting metastatic dissemination through epigenetic activation of the integrated stress response, and a therapeutic opportunity in older patients is revealed.

Shang, Zhao, Ying and colleagues report that the mechanosensor PIEZO1 senses blood shear stress in hematopoietic stem cells, driving proliferation and myeloid bias. This axis links mechanical force to inflammation-induced aging, and PIEZO1 emerges as a potential therapeutic target.

This Review discusses how ageing complicates the already compromised neurogenic lower urinary tract in men with spinal cord injury. The authors present the unique urological challenges faced by this population and propose a patient-centred framework to achieve personalized and lifelong care in these patients.

The dynamics of breast tissue aging are characterized by imaging mass cytometry of over 500 reduction mammoplasties, revealing nonlinear loss of cellularity and a compositional shift favoring inflammation.

Using large-scale UK health records and machine learning, Lian and colleagues identify subtypes of Alzheimer’s and Parkinson’s disease, revealing shared clinical patterns and genetic differences that could support earlier diagnosis and more targeted care.

The mechanisms underlying impaired myelination during aging remain incompletely understood. Here, Gao et al. report that ACSS2-mediated acetate utilization is essential for maintaining the oligodendrocyte progenitor cell pool and facilitating myelination throughout life.

Age-related obesity is a major health issue with unclear causes. This work reveals that the enzyme GSNOR promotes obesity by reducing mitochondria in fat, leading to tissue “whitening” and identifying it as a potential therapeutic target.

Lin et al. identify a mechanism by which swimming exercise attenuates cognitive decline in Alzheimer’s disease mice, via induction of skeletal muscle-derived vesicles containing miR-378a-3p, taken up by microglia to regulate metabolism and enhance plaque clearance.

Werner et al. present the results of the 201 Trial, a 12-week randomized, double-blind placebo-controlled phase 2a study of risvodetinib, in patients with early untreated Parkinson’s disease. Risvodetinib was found to be safe and well tolerated.

Son et al. profile plasma protein structural changes to identify potential conformational biomarkers of Alzheimer’s disease. They report that disease progression, genotype and sex influence structure, and develop a diagnostic panel that tracks disease status.

Pregnancy is associated with stress and multi-system physiological changes. This study used aging clock generated from lab tests to show pregnant females’ apparent age dropped in the first trimester, rose toward delivery, and recovered postpartum.

Dai and colleagues implicate defective dendritic cell migration in impaired vaccine responses in aged mice. Oral delivery of yeast-derived nanoparticles promotes migration of dendritic cells from the gut to lymph nodes and restores vaccine efficacy in aged mice.

This exploratory analysis of a phase 1b study evaluating BIIB080, a MAPT-targeting antisense oligonucleotide, in mild Alzheimer’s disease indicates favorable trends of high-dose BIIB080 in slowing cognitive and functional decline, supporting the need for future trials evaluating clinical efficacy of BIIB080 in mild Alzheimer’s disease.

Turquoise killifish are naturally short-lived vertebrates that serve as a model system for aging. The authors show that killifish exhibit age-related transformation in the immune system, which rapidly develops inflammation, genome instability and functional decline.

Chiche, Djoual, Charifou and colleagues identify a dual role for cell senescence in postpartum tissue remodeling: senescent cells drive mammary gland involution, yet create a permissive niche for tumor initiation, revealing how a conserved repair program can be redirected toward cancer progression.

Aging is characterised by visceral adipose tissue (VAT) inflammation but the molecular mechanisms driving or inhibiting the VAT-driven processes are not fully known. Here the authors identify BAFF as a soluble mediator in VAT to promote the expansion of regulatory B cells that produce IL-10 to inhibit aging-related inflammation.

This Review presents a systems-level framework of how epigenetic dysregulation drives ageing, including through deterioration of nuclear architecture, dysregulation of epigenetic memory, nucleosome alterations and transcription reprogramming. These processes interact and augment gene-expression failures, and thus represent promising potential therapeutic targets.

Concerns over health misinformation online are becoming increasingly important. Here the authors show that older adults are more likely than younger people to encounter low-credibility health information online. Although exposure is limited overall, it is highest among those who already believe inaccurate health claims.

Mitochondrial superoxide production is shown to preserve nuclear envelope integrity by controlling lipid peroxidation, with impact on nuclear and organismal ageing in C. elegans.

Epigenetic clocks are promising biomarkers of biological aging but require longitudinal evaluation. In this longitudinal study, the authors evaluated whether temporal acceleration of multiple epigenetic clocks was associated with mortality, and report that faster increases in several clocks were linked to higher risk of death, independent of baseline epigenetic age and other confounders.

Mejía-Ramírez, Iáñez Picazo, Walter et al. explore how nuclear biomechanical changes limit the regenerative capacity of aged hematopoietic stem cells and show that targeting RhoA rejuvenates aged hematopoietic stem cells by reducing nuclear envelope tension and remodeling nuclear architecture.

Krepelova and colleagues identify an aging- and colon cancer-associated DNA methylation drift in healthy and cancerous human colon samples, echoed in the mouse intestinal epithelium. They show it expands via intestinal cell clonality and is driven by dysregulated iron metabolism.

uPAR is a senescence-associated protein, and CAR T cells targeting uPAR exert senolysis. Here Eskiocak et al. identify uPAR⁺ cells as key targets of intestinal aging and show that CAR T-mediated elimination prevents and restores age-related decline in intestinal regeneration and barrier function.

STAT6 mitigates cellular aging and senescence by regulating the expression of DNA repair genes. However, the upstream signals driving the activation of this non-canonical STAT6 function have not been identified. Here, the authors identify DNA-PK as a key kinase mediating STAT6 phosphorylation in murine and human macrophages and show that this post-translational modification is required to prevent macrophage senescence and protects animals from senescence-driven lung fibrosis and aging.

Exposure to inflammation drives hematopoietic stem cells (HSC) aging, limiting their self-renewal capacity and differentiation. Here, the authors explore the mechanistic link between inflammation and HSC aging. Using mouse models, they identify the innate immune RNA sensor MDA5 as a key mediator of HSC aging and show that MDA5 loss ameliorates the aging phenotype by improving proteostasis in aged HSCs.

González-Gualda, Reinius et al. demonstrate that platinum-based chemotherapy-induced senescence promotes malignancy in ovarian and lung cancer via TGFβ ligands, with evidence in mouse models validated in clinical samples. Concomitantly blocking TGFβ signaling with chemotherapy reduces tumor burden and increases survival in mice.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

This study reveals that the ability to maintain a stable body weight predicts longevity in mice. By tracking weight dynamics throughout life, the authors identify genetic loci linked to body weight, energy homeostasis and healthy aging.

DNA methylation and gene expression data integration identify aging-related genes in blood that predict health outcomes, offering new insights into aging biology and potential therapeutic targets.

By integrating microglial transcriptomics with CSF proteomics, this study reveals protein markers that distinguish early and late Alzheimer’s disease and that have the potential to improve disease tracking and prediction.

Characterizing molecular aging features is crucial for understanding systemic and local factors contributing to the aging process. Here Costa, Chen et al. performed RNA sequencing on 13 tissues across six ages in male and female African turquoise killifish. This sex-balanced killifish aging atlas provides a comprehensive resource for studying aging dynamics across tissues in the killifish—a powerful, short-lived vertebrate model of aging.

Senescent bone marrow stem cells were revealed to exhibit reduced intracellular force, and optimized mechanical stimulation restores this force, enhances FOXO1 chromatin accessibility, and reverses cellular senescence and bone aging.

Using a mouse model with a macrophage-specific DNA repair defect, Niotis, Arvanitaki et al. identify DNA damage-induced autophagy in macrophages as a link from aging to autoimmunity.

Kyriakakis et al. show that bacterial RNA can improve C. elegans healthspan and reduce toxic protein aggregation in muscles. This depends on inter-tissue communication and requires both autophagy and the germline RNAi machinery.