Aging & Longevity

The earliest molecular changes in Alzheimer's disease (AD) are poorly understood^(1-5). Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration. We explored the role of endogenous Li in...

Semantic processing remains relatively preserved during healthy aging, but the mechanisms are poorly understood. Herein, we use dynamic functional mapping based on magnetoencephalography to examine the neural oscillations serving semantic processing across the adult lifespan (N = 154; 21-87 years). Task-related oscillatory dynamics were imaged using a beamformer and whole-brain linear mixed-effects (LME) models were calculated with age and task condition (semantically-related or -unrelated) as...

Cells accumulate mutations throughout development, contributing to cancer, aging, and evolution. Quantitative data on the abundance of de novo mutations within plants or animals are limited, as new mutations are often rare within a tissue and fall below the limits of current sequencing depths and error rates. Here, we show that mutations induced by the maize Mutator (Mu) transposon can be reliably quantified down to a detection limit of 1 part in 16,000. We measured the abundance of millions of...

Mitochondria, cellular powerhouses, harbor DNA [mitochondrial DNA (mtDNA)] inherited from the mothers. mtDNA mutations can cause diseases, yet whether they increase with age in human oocytes remains understudied. Here, using highly accurate duplex sequencing, we detected de novo mutations in single oocytes, blood, and saliva in women 20 to 42 years of age. We found that, with age, mutations increased in blood and saliva but not in oocytes. In oocytes, mutations with high allele frequencies were...

Arterial biomechanical indicators have long been recognized as fundamental contributors to the physiology and pathology of cardiovascular systems. Probing multiple biomechanical parameters of arteries simultaneously throughout the cardiac cycle is highly important but remains challenging. Here, we report a method to quantify arterial anisotropic stiffness, arterial wall stresses, and local blood pressure in a single measurement. With programmed ultrasound excitation and imaging, arterial axial...

The accumulation of senescent cells contributes to morbidity and mortality; however, common mechanisms underpinning this age-associated phenomenon remain elusive. Hematopoietic loss of the Y chromosome (LOY) is the most frequently acquired somatic mutation in males, and this condition has been associated with various age-associated diseases and reduced lifespan. Therefore, we investigated the role of hematopoietic LOY in promoting cellular senescence, focusing on kidney disease because of its...

Unintentional weight loss (UWL) is related to mortality and mobility limitation. Here, we aimed to develop a metabolite-based score for UWL and evaluate its prediction performance and explanation value for UWL-related health outcomes. Participants from the Health, Aging and Body Composition (Health ABC) study with available metabolomics and valid follow-ups were included (N = 2286). First, in the derivation group (N = 1200), 27 of the 77 metabolites associated with incident UWL (> 3% annual UWL...

Several widely used epigenetic clocks have been developed for mice and other species, but a persistent challenge remains: different mouse clocks often yield inconsistent results. To address this limitation in robustness, we present EnsembleAge, a suite of ensemble-based epigenetic clocks. Leveraging data from over 200 perturbation experiments across multiple tissues, EnsembleAge integrates predictions from multiple penalized models. Empirical evaluations demonstrate that EnsembleAge outperforms...

Modern cell therapies are designed to harness natural biology to treat a range of complex diseases. The field of immunology has shown that B cells exhibit multiple unique features, including a natural propensity to interact with and regulate other immune cells, a high capacity to produce proteins, and a long cellular lifespan, which are being creatively applied in engineered B cell (eB cell) therapies. In recent years, advances in genome editing technologies and animal modeling have facilitated...

Aging is a risk factor for the development of chronic diseases; however, it is heterogeneous. Measuring aging in midlife, commonly done using laboratory markers and statistical methods for estimation of biological age (BA), cannot directly inform behavioral intervention goals aiming to promote healthier aging. The Midlife Aging and Performance Study (MAPS) examined the association between an extended, inclusive assessment of physical capacity (PC), as a behavioral marker of aging, and BA,...

Naringin is an antioxidant flavonoid rich in diverse plant species, including citrus plants. While the antioxidant activity of naringin is well documented, there has been limited research on its anti-aging potential. The aim of this study is to investigate the in vivo anti-aging effects of naringin in the budding yeast Saccharomyces cerevisiae as a model. Our findings showed that naringin substantially increased cell viability during the chronological lifespan of wild-type yeast by mitigating...

CONCLUSION: Individuals of advanced age are susceptible to accidents in their domestic environments. A wide spectrum of factors contributes to the occurrence of such accidents. The prevention of home accidents requires an awareness of the risk factors involved, an enhancement of programs designed to facilitate healthy aging, and an increased emphasis on preventive measures. Some lifestyle modifications (exercise, nutritional therapy, home design, and the use of assistive devices) can be employed...

Autophagic decline accompanies age and causes a deterioration in proteostasis, rendering neuronal demise. Rab27 functions as a vesicle regulator for macroautophagic/autophagic degradation and exocytosis. Loss of Drosophila Rab27 in αβp brain neurons enhances longevity, underscoring its neuronal role and systemic effect. To understand the underlying mechanisms, we characterized the cell autonomous and non-autonomous functions of Rab27. Rab27 expression increased in midlife, providing a temporal...

INTRODUCTION: The neural dynamics underlying cognition and behavior change greatly during the lifespan of brain development and aging. EEG is a promising modality due to its high temporal resolution in capturing neural oscillations. Precise prediction of brain age (BA) based on EEG is crucial to screening high-risk individuals from large cohorts. However, the lifespan representation of the EEG oscillatory features (OSFs) is largely unclear, limiting practical BA applications in clinical...

Microglia are the resident immune cells of the brain. Over the past two decades, they have been shown to play critical roles throughout life. Microglia are now considered to be important for brain formation, maturation, activity and plasticity, with outcomes on behavior and other cognitive domains. With this knowledge, microglia represent a promising therapeutic target to promote brain health along an aging trajectory. Emerging evidence also indicates that modifiable lifestyle factors for...

The three-dimensional (3D) genome structure is essential for gene regulation and various genomic functions. CTCF plays a key role in organizing Topologically Associated Domains (TADs) and promoter-enhancer loops, contributing to proper cell differentiation and development. Although CTCF binds the genome with high sequence specificity, its binding sites are dynamically regulated during development, and aberrant CTCF binding is linked to diseases such as cancer and neurological disorders, and...

State-of-the-art membranes derived from polymers of intrinsic microporosity offer promising alternatives to energy-intensive, thermally driven separation techniques but often suffer from reduced performance under condensable gases or physical aging. Here, extrinsically microporous polymer membranes (EMPMs) are introduced as a distinct class of microporous membranes, fabricated from perfluorinated aryl-ether-free aromatic polymers via defluorination-induced thermal cross-linking. This process...

Multi-organ biological aging clocks derived from clinical phenotypes and neuroimaging data have emerged as valuable tools for studying human aging and disease. Plasma proteomics provides an additional molecular dimension to enrich these clocks. In this study, I developed 11 multi-organ proteome-based biological age gaps (ProtBAGs) using 2,448 plasma proteins from 43,498 participants in the UK Biobank. Here I highlight methodological and clinical considerations for developing and using these...

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Older adults are the primary population for cell-based therapies for age-related diseases, but the efficacy of administering autologous mesenchymal stem cells (MSCs) is impaired due to biological aging. In the present study, we cultured aging adipose (AD)-derived MSCs from > 65-year-old donors on extracellular matrix (ECM) synthesized by human amniotic fluid-derived pluripotent stem cells (ECM Plus) versus tissue culture plastic (TCP) and hypothesized that ECM Plus provided an ideal "young"...