Aging & Longevity

Hyperconnectivity in functional brain networks occurs decades before disease onset in Huntington's disease. However, the biological mechanisms remain unknown. We investigate connectivity in Huntington's disease using Morphometric INverse Divergence (MIND) in three Huntington's disease cohorts (N = 512) spanning from two decades before the onset of symptoms through to functional decline. Here, we identify stage-specific profiles, with hyperconnectivity 22 years from predicted motor onset,...

Mutations in mitochondrial DNA (mtDNA) accumulate during aging and contribute to age-related conditions. High mtDNA copy number masks newly emerged recessive mutations; however, phenotypes develop when cellular levels of a mutant mtDNA rise above a critical threshold. The process driving this increase is unknown. Single-cell DNA sequencing of mouse and human hepatocytes detected increases in abundance of mutant alleles in sequences governing mtDNA replication. These alleles provided a...

Inhibitors of DNA methylation such as 5-aza-deoxycytidine are widely used in experimental and clinical settings. However, their mechanism of action is such that DNA damage inevitably co-occurs with loss of DNA methylation, making it challenging to discern their respective effects. Here we deconvolute the effects of decreased DNA methylation and DNA damage on cancer cells, by using degron alleles of key DNA methylation regulators. We report that cancer cells with decreased DNA methylation-but no...

Lithium-ion batteries are pivotal for modern energy storage, yet accurately predicting their lifespan remains a critical challenge. While descriptors like coulombic efficiency are widely used to assess battery longevity, the unclear physical origins of coulombic losses cause semi-quantitative correlation with capacity, complicating battery development. Here, we combine high-precision leakage current and open-circuit-voltage measurements with charge conservation principles to explore microscopic...

A stable and durable ultrafast electron source is highly desirable for sophisticated vacuum electron technologies. However, free-space excitations based on ultrahigh-power or deep-ultraviolet pulsed lasers usually cause cathode material damage and mechanical vibration even under ultrahigh vacuum. In this work, we present a compact ultrafast electron source consisting of graphene integrated on an optical fiber, taking advantage of the ultrafast hot-electron emission from graphene and well-defined...

Influenza virus infection contributing to the majority of viral pneumonia, acute cardiovascular and renal co-morbidities even death, is a worldwide public health concern caused by seasonal and pandemic influenza viruses. Unlike seasonal influenza, which occurred annually, the emerging of pandemic influenza every two to three decades for the distinctly reassorted influenza virus strains contributed to the broadly rapid spread and increased morbidity and mortality. While the majority of the...

This study analyzed UK Biobank data from 46,463 postmenopausal women to investigate metabolic changes linked to years since menopause (YSM) and their impact on aging biomarkers. Elastic net regression identified 115 YSM-associated metabolites, forming a metabolic signature strongly correlated with YSM (r = 0.30, P < 0.001). Each standard deviation increase in this metabolic signature was associated with decreased odds of long telomere length (0.94, 0.92-0.96), increased odds of high allostatic...

As global aging accelerates, frailty and depressive symptoms have emerged as critical contributors to cardiovascular disease (CVD) risk among older adults. However, the dynamic interplay between these factors remains underexplored. Here, we examine the associations among frailty, depressive symptoms, and incident CVD using data from five international cohorts (HRS, CHARLS, SHARE, ELSA, MHAS) involving individuals aged 50 and above. Our findings reveal that frailty significantly increases CVD...

Neuronal senescence (i.e., neurescence) is an important hallmark of aging and neurodegeneration, but it remains poorly characterized in the human brain due to the lack of reliable markers. This study aimed to identify neurescence markers based on single-nucleus transcriptome data from postmortem human prefrontal cortex. Using an eigengene approach, we integrated three gene panels: (a) SenMayo, (b) canonical senescence pathway (CSP), and (c) senescence initiating pathway (SIP), to identify...

The impact of exogenous stressors, such as cancer chemotherapies, on the genomic integrity and clonal dynamics of normal hematopoiesis is not well defined. We conducted whole-genome sequencing on 1,276 single-cell-derived hematopoietic stem and progenitor cell (HSPC) colonies from ten patients with multiple myeloma treated with chemotherapies and six normal donors. Melphalan treatment significantly increased the mutational burden, producing a distinctive mutation signature, whereas other...

Several chemotherapeutic agents act by increasing DNA damage in cancer cells, triggering cell death. However, there is limited understanding of the extent and long-term consequences of collateral DNA damage in normal tissues. To investigate the impact of chemotherapy on mutation burdens and the cell population structure of normal tissue, we sequenced blood cell genomes from 23 individuals aged 3-80 years who were treated with a range of chemotherapy regimens. Substantial additional somatic...

BACKGROUND: Older adults with cancer struggle to maintain recommended levels of physical activity and nutrition during treatments. Collecting data in a real-life context provides a better understanding of the motivational and behavioral dynamics of this population, which is underrepresented in clinical trials. Ecological momentary assessment (EMA) is a frequently used approach to collect repeated measures in real time in a naturalistic environment. This approach can provide insights into the...

CONCLUSIONS: Our study suggests an ancient and conserved role for these core TEs as self-renewing components of animal chromosomes.

DNA methylation can give rise to robust biomarkers of aging, yet most studies profile it at the bulk tissue level, which masks cell type-specific alterations that may follow distinct aging trajectories. Long-read sequencing technology enables methylation profiling of extended DNA fragments, enabling mapping to their cell type of origin. In this study, we introduce a framework for evaluating cell type-specific aging using long-read sequencing data, without the need for cell sorting. Leveraging...

The field of longevity interventions has witnessed rapid expansion, driven by scientific advancements alongside growing industry and consumer interest. However, no longevity intervention has yet been proven effective or ready for widespread clinical adoption. A substantial gap persists between public expectations and the current scientific realities. This article explores four key themes: (1) consumer priorities regarding longevity interventions, (2) the type and depth of scientific information...

The aging process results in a gradual decline in brain function, characterized by heightened hippocampal atrophy and dysfunction. Physical activity can enhance cognitive skills in elderly individuals and is significant in the prevention of neurodegenerative illnesses. Hawthorn (Crataegus oxyacantha) is a fruit-bearing shrub with a longstanding history as a medicinal agent. Currently, hawthorn is predominantly utilized for a range of pathological diseases. This research is designed to assess the...

Aging leads to a decline in physiological reserves, an increase in age-related diseases, reduced functional ability and a shortened healthspan. While molecular markers of chronological aging exist, their link to general health and intrinsic capacity (IC), a composite measure of physical and mental capacities, remains unclear. This study integrates the WHO's Healthy Aging framework with geroscience to explore fibroblasts as indicators of health. We assessed primary skin fibroblasts from 133...

Satellite glial cells (SGCs) are peripheral nervous system glial cells enveloping sensory and sympathetic ganglion neuronal soma. Traditionally viewed as mere supportive cells, recent studies reveal SGCs' dynamic role in regulating sensory and autonomic processing, positioning them to shape peripheral neural signaling. This role has the potential to impact the healthy function of numerous biological processes and contribute to disease progression. Studies now implicate peripheral sensory and...

The mammalian/mechanistic target of rapamycin (mTOR) is an evolutionarily conserved multi-node signaling pathway that integrates critical environmental cues to control cellular growth. Decades worth of studies have intricately dissected the mTOR pathway to identify regulatory signals that are essential for regulating immune cell activation, differentiation, and function. As the mTOR field continues to evolve, so too does our understanding of these new findings in immune cells. Our group and...

Plant biomass and its allocation are fundamental for understanding biospheric matter production. However, the impacts of atmospheric phosphorus (P) deposition on species-specific biomass and its allocation in global terrestrial plants remain unclear. By synthesizing 5548 observations of plant biomass and its allocation related to P addition worldwide, we find that P addition increases plant biomass by an average of 35% globally. This increase varies across plant functional groups, with stronger...