Aging & Longevity

In this meet-the-author Q&A, Scientific Editor Sara Rohban and Editor-in-Chief Laura Zahn speak with Junyue Cao about his Cell Genomics paper. He discusses his ambitions to study aging and how his newly developed method, EnrichSci, was used to look at changes over time in oligodendrocytes in the brain.

Aging is associated with oxidative stress, but specific druggable pathways remain elusive. Here, we define a conserved iron-lipid axis driving primate aging, termed "ferro-aging." Multi-tissue profiling in humans and non-human primates reveals age-progressive iron accumulation, fueling chronic lipid peroxidation orchestrated by acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4). Distinct from acute ferroptosis, this ACSL4-mediated process promotes cellular senescence and...

Aging is a major risk factor for neurodegenerative diseases, yet the underlying epigenetic mechanisms remain unclear. Here, we generated a comprehensive single-nucleus cell atlas of brain aging across multiple brain regions, comprising 132,551 single-cell methylomes and 72,666 joint chromatin conformation-methylome nuclei. Integration with companion transcriptomic and chromatin accessibility data yielded a cross-modality taxonomy of 36 major cell types. We observed that transposable element (TE)...

Mitochondrial disease encompasses inherited disorders affecting mitochondrial function. A severe and untreatable form of mitochondrial disease is Leigh syndrome (LS), causing psychomotor regression and metabolic crises. To accelerate drug discovery for LS, we screen a library of 5,632 repurposable compounds in neural cells from LS-patient-derived induced pluripotent stem cells (iPSCs). We identify phosphodiesterase type 5 (PDE5) inhibitors as leads and prioritize sildenafil for its clinical...

CONCLUSIONS: The effects of PM(2.5) exposure on the skeletal muscle system are age-specific, with distinct damaging effects during growth and aging, whereas skeletal muscles in middle-aged mice are resistant to PM(2.5)-induced damage.

The ageing global population faces a rising prevalence of chronic kidney disease (CKD), now recognized as a state of accelerated ageing driven by chronic low-grade inflammation-inflammaging. This review synthesizes current evidence positioning the kidney not merely as a passive target but as an active participant in systemic inflammaging, a process fueled by immunosenescence, metabolic reprogramming, and cellular senescence. We explore how resident renal cells, including tubular epithelial...

Aging alters prefrontal recruitment, often showing posterior-anterior shifts that may reflect compensatory mechanisms. Working memory capacity (WMC) is a key individual difference shaping attention and control but its role in age-related functional reorganization remains unclear. We examined 72 adults (36 younger, 36 older) who completed standardized span tasks and an fMRI visual discrimination paradigm with three manipulations: perceptual load, fine discrimination, and mapping-switch....

Balance training in geriatric rehabilitation reduces fall risk by eliciting multifaceted cortical reorganization through repeated sensorimotor challenges, supporting more efficient postural control in aging. This study combined minimum spanning tree (MST) and k-iteration second-best MST analyses to characterize training-induced changes in cortical network efficiency and resilience. Twenty-four older adults (70.4 ± 3.3 years) completed 12 sessions of stabilometer training with real-time visual...

The dynamic changes in immune cell composition throughout the human lifespan remain poorly understood. Here, we performed single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing on peripheral blood mononuclear cells from healthy donors, spanning mid-fetal to late adulthood. Our findings revealed age-associated reprogramming across lymphoid and myeloid lineages, with T cells undergoing the most significant transcriptional remodeling. Notably,...

Awards intended to "build the train tracks" for approval of therapies to extend healthy life.

Mapping behavior of individual vertebrate animals across lifespan could provide an unprecedented view into the lifelong process of aging. We created a platform for high-resolution continuous behavioral tracking of the African killifish across natural lifespan from adolescence to death. We found that animals follow distinct individual aging trajectories. The behaviors of long-lived animals differed markedly from those of short-lived animals, even relatively early in life, and were linked to...

Stroke is one of the leading causes of mortality and disability worldwide, with ischemic stroke accounting for over 87% of all stroke cases. Chronic kidney disease (CKD) is one of the major risk factors for stroke, as CKD patients have shown evidence of impaired cerebral autoregulation leading to exacerbated stroke pathology. The worsening of stroke outcomes in CKD patients is limitedly understood. Inflammation plays a pivotal role in driving the CKD-stroke pathology. The cGAS-STING (cyclic...

Intrinsic capacity is a concept established by the World Health Organization (WHO). The concept aims to represent the total of a person's physical and mental abilities, measured across five domains: cognition, psychological, sensory, vitality, and locomotor that were identified as crucial for healthy aging. The aim being to shift focus from disease to function to predict health, disability, and frailty. In this large-scale cohort study, we aim to investigate the association between intrinsic...

Ageing is accompanied by declining memory function, with extremely heterogeneous manifestation in the human population¹. Brain-extrinsic factors influencing cognitive decline, such as gastrointestinal signals, have emerged as attractive targets for peripheral interventions^(2-6), but the underlying mechanisms remain largely unclear. Here, by charting a high-resolution map of microbiome ageing and its functional consequences throughout the lifespan of mice, we identify a mechanism by which...

Lung cancer predominantly affects older individuals, yet how physiological ageing influences tumour evolution remains poorly understood¹. Here we show that 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 (ISR). The ISR effector ATF4 drives epithelial and metabolic plasticity, conferring metastatic competence. Mechanistically,...

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Major depressive disorder (MDD) is associated with widespread alterations in functional brain networks across the lifespan. However, heterogeneity in atypical brain development among patients with MDD remains largely uncharacterized. Using a multisite resting-state functional MRI dataset consisting of 1,105 MDD patients and 1,065 healthy controls, we constructed a harmonized multicenter brain age prediction model based on individualized functional topography and identified two patient subgroups...

Phenotypic heterogeneity is prevalent during aging, yet its underlying molecular drivers remain poorly understood. In budding yeast, two distinct aging trajectories, characterized by either ribosomal DNA (rDNA) instability or mitochondrial decline, have been proposed to be mutually exclusive. Here, we systematically dissect the heterogeneity among aging yeast cells by combining single-cell transcriptomics with longitudinal fluorescence microscopy. Our data reveal distinct transcriptional...