Aging & Longevity

Chronological aging is a major source of interindividual biological variability, yet the metabolic background that accompanies aging in women remains incompletely defined. Using large-scale plasma metabolomic and lipidomic profiling across the adult female lifespan, this study identifies coordinated metabolic signatures that progressively emerge with aging and dominate systemic metabolic variability independently of body mass index and estradiol status. Aging was associated with consistent...

Mitochondrial dysfunction and epigenetic alterations play critical roles in aging-related diseases, yet the molecular mechanisms linking mito-nuclear crosstalk to ovarian aging remain poorly understood. Here, single-cell transcriptome analysis of aging ovaries revealed senescence-associated hallmark alterations, including abnormally elevated mitochondrial metabolism, disrupted histone modification patterns, and enrichment of the senescence-associated secretory phenotype (SASP). We demonstrated...

Oncogene-directed therapies can induce profound tumor regression in oncogene-addicted cancers, but their long-term benefit is often limited by resistance and relapse. Here we show that oncogene inactivation rapidly induces senescence and a pro-inflammatory senescence-associated secretory phenotype (SASP). In vivo, oncogene inactivation-induced senescence (OIIS) predisposes tumors to relapse, accompanied by polyploidy, chromosomal instability, acquisition of alternative oncogenic pathways...

Aging affects lung function, predisposing older adults to respiratory diseases; however, the cellular and molecular mechanisms of lung aging are not fully understood. Leveraging single-cell and spatial transcriptomics data from 184 and 70 lung parenchyma samples, respectively, we present an analytical platform to dissect the cell composition, gene expression modules, and regulatory changes linked to multiple hallmarks of lung aging. Our findings show cell type-specific age-association of...

Bifunctional glycosylases, OGG1 for purines and NTH1 for pyrimidines, repair oxidized DNA bases via consecutive glycosylase and AP-lyase reactions, yet their catalytic relationships and lyase activity's biological relevance remain unresolved. Here, we solved crystal structures of archaeal and human Ogg1 and Nth1 captured in key damage-recognition and catalysis-ready states, complemented by ab initio molecular dynamics simulations of their complete reaction trajectories. We thereby define a...

Lysosomes are essential regulators of cellular homeostasis. Emerging evidence positions lysosomes as both vulnerable targets and active drivers of ageing biology. During ageing, lysosomes exhibit impaired biogenesis, defective acidification, reduced hydrolytic activity and compromised membrane integrity. These defects impair the clearance of damaged organelles and macromolecules and promote cellular stress responses, inflammageing and senescence, causing age-dependent functional decline across...

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CONCLUSION: The contextually relevant framework derived from this study can help identify reasons for older adults' reluctance or inability to access elderly care services at health centers. Future studies can apply the proposed framework to thoroughly examine the challenges of implementing the national aging care program across various universities of medical sciences in Iran.

Quantifying biological aging requires biomarkers that capture multisystem physiological decline beyond chronological age. We aimed to compare the prognostic performance of plasma proteomics, metabolomics, and conventional clinical risk factors for all-cause mortality, and to characterize molecular pathways associated with mortality risk and age-related physiological decline. Untargeted plasma proteomics and metabolomics were profiled in 848 community-dwelling adults from the I-Lan Longitudinal...

The extremely short life span of neutrophils is critical for immune homeostasis and immune defense against pathogens, but the molecular mechanisms underlying this phenomenon are not fully understood. Here we report that TNFAIP8 (TNF-α-induced protein 8) family of polarity proteins regulates neutrophil homeostasis by propagating phosphoinositide signaling. Genetic deletion of two members of the TNFAIP8 family, i.e., TIPE0 and TIPE1, resulted in spontaneous neutrophilia and hepatitis. TNFAIP8...

Intracortical microstimulation (ICMS) of somatosensory cortex can restore a sense of touch to people with spinal cord injury. In this early feasibility clinical trial (NCT01894802), we evaluated the safety, efficacy, and longevity of ICMS because there is a paucity of such long-term studies in humans. This information is crucial to the development of clinical neuromodulation devices, particularly for restoring touch, hearing, and vision. ICMS was delivered to five participants with spinal cord...

Brain age estimation using machine learning has gained significant attention as a promising approach to assess cognitive health and aging. By analyzing structural and functional MRI data, these models can predict an individual's brain age, providing insights into neurological conditions and potential interventions. The purpose of this study is to compare the performance of different MRI modalities in predicting brain age and to determine the relative importance of specific brain regions. In this...

Microglia maintain neuronal homeostasis through dynamic surveillance strategies that depend on their functional state. In the healthy brain, highly ramified microglia monitor neuronal integrity via motile processes and transient soma contacts. Aging is associated with reduced process motility and diminished expression of homeostatic markers, raising the question of how microglial surveillance adapts to these changes. Here, we used ex vivo time-lapse imaging of acute cortical slices from young...

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been...

Aging and chronic inflammation alter hematopoiesis, impacting the hematopoietic progenitor populations in the bone marrow. In this issue of Immunity, Yao et al. show that the canonical type 2 cytokine interleukin 4 reverses age-related hematopoietic and physiologic effects by rebalancing progenitor fates.

Inflammasomes, particularly the NLRP3 complex, play a central role in coordinating innate immune activation and neuroinflammatory responses within the cytosol. Persistent or dysregulated nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) activation promotes caspase-1-dependent maturation of interleukin (IL)-1β and IL-18 and triggers gasdermin D (GSDMD)-mediated pyroptosis, thereby contributing to the pathogenic cascades underlying Alzheimer's disease...

Cellular senescence is a hallmark of aging and a contributing factor to many age-related morbidity and decline. A key characteristic of senescent cells is a pro-inflammatory secretome known as the senescence-associated secretory phenotype (SASP). When tracked in circulation, SASP factors associate with age-related clinical traits and diseases, raising the captivating possibility that the senescence burden, and concomitant susceptibility to age-related morbidity, can be noninvasively assessed in...

The pursuit of high-energy-density lithium-ion batteries demands high-silicon silicon-graphite composite negative electrodes, yet their commercialization remains hindered by interfacial incompatibility and mechanical instability. While an ideal binder must simultaneously achieve robust adhesion to both silicon and graphite, accommodate substantial silicon volume changes, and maintain high binder bulk stability, existing systems fail to harmonize these requirements. Here, we present a molecularly...

Too much or too less lipid deposition increases mortality, while in contrast, modest lipid deposition during aging is crucial for healthspan. How animals determine the aging state and then promote appropriate lipid deposition for lifespan benefits are largely unknown. In this study, we identified citrulline as a key metabolite driving aging-related lipid deposition for healthspan in Caenorhabditis elegans. Citrulline deficiency reduced aging-related lipid accumulation and shortened lifespan, an...