Aging & Longevity

Cancer treatments are improving, and the population of cancer survivors is steadily increasing. However, many survivors experience long-term side effects, including chemobrain and other age-related geriatric disorders like cognitive impairment (CI), severely impacting their quality of life. Emerging studies suggest that the gut microbiome plays a central role in cognitive health. However, the long-term effects of cancer treatments on the microbiome, and how these changes impact cognitive health...

Endothelial metabolism underpins tissue regeneration, health, and longevity. We uncover a nuclear oxidative catabolic pathway linking cystine to gene regulation. Cells preparing to proliferate upregulate the SLC7A11 transporter to import cystine, which is oxidatively catabolized by cystathionine-γ-lyase (CSE) in the nucleus. This generates acetyl units via pyruvate dehydrogenase, driving site-specific histone H3 acetylation and chromatin remodeling that sustain endothelial transcription and...

Aging is an essential aspect of human life, and studying its mechanisms is crucial for extending lifespan and improving quality of life. The immune system plays a central role in the onset of age-related diseases. Understanding the differences between healthy and dysfunctional aging provides key insights into the fundamental immune alternations that occur prior to the point where the system begins to fail. In this review, we explore current perspectives on human immune aging. We focus on changes...

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. In AD, there is a gradual impairment of memory and cognitive function that interferes with daily living. The pathophysiology of AD revolves around complex interactions between amyloid-β (Aβ) overproduction and accumulation, followed by tau hyperphosphorylation, which together promote a cascade of neuronal dysfunction and degeneration. AD has two forms, sporadic and familial, with genetic variants such as triggering...

Senescent cells (SnCs) contribute to various age-related diseases, such as osteoarthritis (OA), a degenerative joint condition that causes persistent pain and reduces physical functioning in older adults. The pathogenesis of OA includes subchondral bone remodeling, synovial inflammation, and cartilage breakdown. Cellular senescence, particularly the pro-inflammatory senescence-associated secretory phenotype (SASP), may have a pivotal role in the progression of OA. SASP factors could exacerbate...

The biology of individual lipid species and their relevance in Alzheimer's disease (AD) remains incompletely understood. To explore the lipidomic biomarkers associated with cognition function and neuropathological changes in AD, we utilize non-targeted mass spectrometry on 316 post-mortem brains from participants in the Religious Orders Study (ROS) or Rush Memory and Aging Project (MAP) cohorts classified as control, asymptomatic AD (AAD), or symptomatic AD (SAD), and integrate the lipidomics...

Forest restoration is increasingly promoted to mitigate climate change, conserve biodiversity, and secure food and water sovereignty. Yet many restored forests do not persist in the long term, and the role of land tenure regimes in shaping these outcomes remains poorly understood. We examine restoration reversals (restored forests later deforested) and long-term restoration gains (restored forests that remained intact) across 1.9 million territories in Brazil's Atlantic Forest from 1985 to 2022....

While existing studies have linked declines in intrinsic capacity (IC) to adverse health outcomes, the role of potentially modifiable lifestyle factors in this pathway, especially sedentary behavior, remains critically underexplored. Using data from the Beijing Longitudinal Disability Survey in Community Elderly (BLINDSCE) cohort (2023-2024), this study investigated both cross-sectional and 1-year longitudinal associations between sedentary time and IC in community-dwelling older adults. Of the...

Dendritic arbors are essential for neuronal computation and signal propagation, yet large-scale single-neuron morphology studies remain challenging. Here we present a systems biology approach, termed 'dendritome mapping', to profile the dendritic morphology of genetically defined single neurons in mice, unveiling striatal medium spiny neuron (MSN) morphological territories and aging-associated or disease-associated alterations. We generated 3,762 three-dimensional-reconstructed and...

Mitochondrial dysfunction and stem cell exhaustion contribute to age-related immune decline, yet clinical interventions targeting immune aging are lacking. Recently, we demonstrated that urolithin A (UA), a mitophagy inducer, expands T memory stem cells (T(SCM)) and naive T cells in mice. In this randomized, double-blind, placebo-controlled trial, 50 healthy middle-aged adults received oral UA (1,000 mg day^(-1)) or placebo for 4 weeks; time points of analysis were baseline and day 28. Primary...

Despite its rapid economic rise over the past four decades, China now grapples with the challenge of accommodating and supporting its expanding aging population. In 2020, 18% of its population were over age 60, and 2.5% were over age 80, projected to rise to 39% and 10%, respectively, by 2050. This demographic shift places China at the forefront of diverse individual, familial and societal challenges. Here, we review these challenges in the context of emerging breakthroughs in basic and...

DNA modifications drive aging, neurodegeneration, carcinogenesis and chemotherapy drug action. Accurate mapping of diverse DNA modifications with single-nucleotide precision in complex genomes remains challenging. We upgraded click-code-seq, a click-chemistry-aided DNA-modification mapping strategy, to enable its first application for sequencing oxidation and depurination in the human genome. We developed a companion fluorescence assay, click-fluoro-quant, to rapidly quantify common DNA...

BACKGROUND: With the acceleration of population aging, identifying and addressing the unmet assistance needs of home-dwelling older adults has become increasingly important. This study aimed to develop and validate a reliable and practical assessment tool to identify such needs.

CONCLUSIONS: This set of core needs screening items can potentially reduce the heterogeneity of needs and risk assessments across studies and clinical practices and inform the development of a standardized need screening tool.

Cerebral small vessel disease (SVD) is frequently comorbid with Alzheimer's disease (AD), and brain endothelial cells (BECs) express genes associated with AD genetic risk. However, the epigenome of neurovascular cells and its intersection with genetic risk remain unexplored. Here, we generated gene regulomes for human BECs, mural cells, and other brain cell types and showed that AD heritability is primarily immune related, with a modest BEC enrichment. On the other hand, SVD heritability is...

The Centers for Medicare & Medicaid Services' (CMS) Guiding an Improved Dementia Experience (GUIDE) Model represents a landmark opportunity to improve outcomes for persons with dementia and their caregivers and scale comprehensive dementia care through a structured service delivery and alternative payment approach. The National Dementia Care Collaborative (NDCC), a coalition of scientific and clinical leaders in evidence-based dementia care, works to promote comprehensive dementia care. Drawing...

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, fatal genetic disorder characterized by accelerated aging. The accumulation of an abnormal and toxic protein called progerin within HGPS nuclei disrupts cellular processes, including gene expression and DNA repair. Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defense, is one of the hallmarks of HGPS. To identify novel molecular mechanisms underlying HGPS pathogenesis, we...

One of the key hallmarks of aging is the breakdown of proteostasis-the finely tuned balance of protein synthesis, folding, trafficking, and degradation that maintains proteome integrity and cellular function. In this study, we employed ^(15)N metabolic labeling to assess protein turnover in young and aged mice. Among the proteins examined, cystatin C exhibited the largest age-related reduction in turnover, alongside decreases in other proteins involved in neuroprotection, structural stability,...

Shorter leukocyte telomere length (LTL) is associated with aging-related cardiovascular diseases, but its relationship with heart failure with preserved ejection fraction (HFpEF) in high-risk Chinese patients with hypertension under 65 years remains unclear. In this observational prospective study, we investigated 646 patients with hypertension aged < 65 years with diabetes, coronary heart disease (CHD), or ≥ 3 cardiovascular risk factors. Baseline assessments included clinical evaluation,...

Tardigrades survive extreme environments partly through the damage suppressor (Dsup) protein, which protects DNA from ionizing radiation and oxidative stress. Dsup is largely unstructured but binds nucleosomes to shield DNA from damage. To investigate its protective role in a whole organism, we expressed the Ramazzottius varieornatus Dsup gene in the nematode Caenorhabditis elegans. Transgenic worms tolerated x-ray exposure and oxidative stress without apparent toxicity and exhibited a notable...