Aging & Longevity

Long-lived wild rodents closely related to laboratory mice on the evolutionary scale may allow identification of dormant pathways that resist aging. Spiny mice (Acomys) are known for their exceptional regenerative capacity, but their resilience to aging is unknown. Here, we report that aged golden spiny mice (Acomys russatus), reared in a non-pathogen-free environment, resist functional decline, have a greater repair capacity with reduced senescence in immune-metabolic organs compared to their...

The blood-brain barrier (BBB) is crucial for brain homeostasis, and its dysfunction is associated with aging and neurodegenerative diseases. A recent seminal study by Shi et al. (2025) published in Nature illuminates a previously underappreciated component, the brain endothelial glycocalyx, as a key player in age-related BBB breakdown. They demonstrated that aging and neurodegenerative disease can lead to significant structural and compositional dysregulation of the brain endothelial glycocalyx,...

The existence of human hippocampal neurogenesis has long been disputed^(1-12) and its relevance in cognition remains unknown. Recent studies have established the presence of proliferating progenitors and immature neurons and a reduction in the latter in Alzheimer's disease (AD)^(11,13). However, their origin and the molecular networks that regulate neurogenesis and function are poorly understood. Here we studied human post-mortem hippocampi obtained from different cohorts: young adults with...

Transposable elements (TEs) in the human genome are the heritage of ancient parasitic infections. While most of human DNA comprises TEs and TE-derived elements, their repetitive nature poses technical challenges; thus, little is known about their positional identity and regulatory roles. Here, by integrating long-read and multidimensional transcriptional analyses, we investigate when, where and how TEs become part of a gene. We characterize how TE-derived isoforms change across mouse-human...

Biological aging reflects complex cellular and biochemical processes that can be measured across multiple omic layers. Using routine clinical laboratory data from ~31,000 participants in the Mass General Brigham Biobank, we developed EMRAge, a biomarker of mortality risk that can be broadly recapitulated across electronic medical records. Here we show that EMRAge can be modeled using elastic net regression with DNA methylation and multi-omics to generate DNAmEMRAge and OMICmAge, respectively....

Neuroplasticity, the brain's capacity to adapt and reorganize in response to experiences and environmental changes, is fundamental to cognitive aging. As individuals age, cognitive functions such as memory, processing speed, and executive function commonly decline, driven largely by changes in neuroplasticity mechanisms like synaptic plasticity, neurogenesis, and functional reorganization. Synaptic plasticity is a well-established mechanism supporting learning and memory across the lifespan,...

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Increased life expectancy brought about by improved healthcare and lifestyle has heightened the challenge of neurodegenerative disorders like Alzheimer's disease (AD) and other age-related disorders. Neurodegeneration is known to be accompanied by loss of memory, changes in brain morphology, and neuroinflammation, and multiple factors contribute to the progression and pathogenesis of the condition. Of these factors, metabolic dysregulation is known to influence the process, but the precise...

To investigate the relevance of small RNAs to human longevity, we pursued three goals: (a) to validate epigenetic (small RNA) factors underlying survival of older adults, (b) to develop and validate prediction models of survival for potential clinical application, and (c) to identify plausible druggable targets prolonging longevity. We evaluated 828 small non-coding RNAs-687 microRNAs (miRNAs) and 141 piwi-interacting RNAs (piRNAs)-in baseline plasma from 1271 community-dwelling older adults (≥...

Macrophage senescence drives inflammaging, a chronic, age-related inflammation. To date, the protective mechanisms against inflammaging are poorly defined. Here, we identify DNA-PK-mediated phosphorylation of murine STAT6 at serine 807 (Ser807) as a crucial post-translational modification for preventing macrophage senescence. Ser807 phosphorylation blocks STAT6 ubiquitination-mediated degradation and promotes STAT6 partnering with PU.1 to activate DNA repair genes. Macrophages lacking Ser807...

Metabolic activity shapes cell fate but remains challenging to capture in vivo with high resolution. Here we performed longitudinal metabolic and phenotypic profiling of human antigen-specific CD8^(+) T cells after yellow fever vaccination using flow cytometry and single-cell RNA sequencing. As assessed by protein translation rates, CD8^(+) T cells upregulated glycolysis to fuel anabolic needs for proliferation but predominantly used oxidative phosphorylation for energy production during the...

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The aging brain depends on coordinated fluid transport, immune surveillance, and clearance of metabolic byproducts to preserve cognitive and physiological homeostasis. While peripheral lymphatic decline is well established, growing evidence implicates brain-draining lymphatic pathways, particularly meningeal lymphatic vessels and their downstream drainage to deep cervical lymph nodes, as an aging-sensitive axis that intersects with neuroinflammation and neurodegenerative vulnerability. Here, we...

CONCLUSIONS AND IMPLICATIONS: Dynapenia in older men and sarcopenia in older women were independently associated with mortality, highlighting sex-sensitive prognostic differences and underscoring the need of phenotype-specific strategies for healthy ageing.

Multiplexed protein imaging enables spatial analysis of complex tissues, but detecting proteins expressed at low levels remains challenging, particularly in widely available formalin-fixed, paraffin-embedded (FFPE) specimens. Many biologically important regulators-including senescence markers, transcription factors, and secreted proteins-are therefore difficult to study in situ using existing high-plex methods. Here we show that integrable Co-detection of Low-Abundant Proteins (iCLAP) enables...

Biological aging and immunosenescence are central to longevity, yet their interplay in centenarians remains unclear. We conducted a cross-sectional study in 160 Colombian centenarians to examine associations between biological age (PhenoAge), immunosenescence and age-related clinical variables. Cytokine profiling (n = 114) and lymphocyte immunophenotyping (n = 42) were assessed. It was observed that better QoL and well-being were significantly associated with lower biological age, while...

Postural control depends on the integration of visual and proprioceptive inputs, yet how aging modifies this sensorimotor integration in upright standing remains unclear. We examined age-related differences in postural responses to visual and proprioceptive disturbances during upright standing by applying (i) bilateral Achilles or tibialis anterior tendon vibration and (ii) and simulated forward or backward self-motion in a virtual environment. Eighteen young [22.8 (1.6)yr] and eighteen old...

Visible light influences a range of physiological processes, yet how animals respond to it independently of the visual system remains largely unknown. Here, we uncover a previously undescribed light-induced transcriptional pathway that modulates behavioral plasticity in Caenorhabditis elegans, a roundworm without eyes. We demonstrate that ambient visible light or controlled-intensity visible-spectrum LED activates an effector gene cyp-14A5 in non-neuronal tissues through the bZIP transcription...