Aging & Longevity

Hematopoietic stem cells (HSCs) with mutations that can cause clonal hematopoiesis of indeterminate potential (CHIP) accumulate during aging. Agarwal et al.¹ demonstrate in Nature that intestinal barrier permeability increases with age and enables the microbial metabolite ADP-heptose to reach the bone marrow, thus driving the expansion of DNMT3A-mutant HSCs.

Epigenome-wide association studies (EWASs) are transforming our understanding of the interplay between epigenetics and complex human traits. We introduce the methylation screening array (MSA) to enable scalable and quantitative screening of trait-associated DNA cytosine modifications in large human populations. The MSA integrates EWASs and cell-type-linked methylation signatures, covering diverse traits and diseases. Using the MSA to profile the ternary-code DNA methylations-dissecting...

Disseminated tumor cells (DTCs) can remain in a non-proliferative, dormant state for years in distant organs, but the exogenous causes triggering their reactivation and metastatic colonization are unclear. Here, we demonstrate that chemotherapeutic drugs, including doxorubicin and cisplatin, enhance proliferation and lung metastasis of dormant breast cancer cells. Using a recombinase-based dormancy tracing system, DormTracer, we confirm chemotherapy-induced reactivation of dormant DTCs leading...

BRAF and MEK inhibitors (BRAF/MEKi) have radically changed the treatment landscape of advanced BRAF mutation-positive tumours. However, limited efficacy and emergence of drug resistance are major barriers for successful treatments. Here, by using relevant preclinical models, we find that Connexin43 (Cx43), a protein that plays a role in cell-to-cell communication, enhances the effectiveness of BRAF/MEKi by recruiting DNA repair complexes to lamin-associated domains and promoting persistent DNA...

Taurine is a conditionally essential nutrient and one of the most abundant amino acids in humans, with diverse physiological functions. The cellular uptake of taurine is primarily mediated by the taurine transporter (TauT), and its dysfunction leads to retinal regeneration, cardiomyopathy, neurological and aging-associated disorders. Here we determine structures of TauT in two states: the apo inward-facing open state and the occluded state bound with substrate taurine or γ-aminobutyric acid...

Mobility is a cornerstone of health and quality of life, particularly in older adults. Digital mobility outcomes (DMOs) from real-world walking data offer crucial insights into the functional status and early markers of mobility decline. This study provides reference values for walking activity, pace, rhythm, and gait bout-to-bout variability in community-dwelling older adults and evaluates the effects of age, sex, height, and weight on these parameters. Using data from 200 older adults (aged...

We constructed a polygenic protective score specific to Alzheimer's disease (AD PPS) based on the current literature among the participants enrolled in five studies of healthy aging and extreme longevity in the USA, Europe, and Asia. This AD PPS did not include variants on apolipoprotein E (APOE) gene. Comparisons of AD PPS in different data sets of healthy agers and centenarians showed that centenarians have stronger genetic protection against AD compared to individuals without familial...

One of the prokaryotic partners at the origin of eukaryotes was an archaeon, but do archaea age, and if so, how? Uncovering aging in Archaea might provide more general clues about cellular senescence and rejuvenation and their origins. To fill this knowledge gap, we focused on Saccharolobus islandicus, a model archaeon for which the cell cycle can be synchronized and controlled. We generated longitudinal transcriptomes of synchronized S. islandicus populations that capture typical expression and...

CONCLUSIONS: Both patient- and healthcare system–related factors were associated with delayed surgery for hip fractures in older adults. Although a reimbursement incentive has been introduced to promote early surgery, real-world challenges, including preoperative risk factors and hospital resources, continue to affect surgical timing. These findings could help inform strategies to enhance timely surgical care for older patients with hip fractures in aging societies.

CONCLUSION: This study offers valuable insights into the health-related needs and indicators of an age-friendly city for older adults in a province in Iran. The results can guide managers, policymakers, and planners in developing effective strategies for elderly care at both national and regional levels.

Exergames (EG) are interactive video games that require physical activity and use gamification to make exercise more engaging. EG interventions demonstrated various benefits for older adults including improved mental health, quality of life, and a reduced risk of falls. Enhanced cognition is considered one of the principal targets driving these benefits. This systematic review aimed to identify the neurobiological effects of EG interventions in healthy older adults and those with neurocognitive...

Osteoimmunology is an interdisciplinary study of the interaction between the immune system and the skeletal system, aiming to reveal the immune regulation mechanisms that affect bone health and disease. Aging is a macro concept, which is not limited to the senescence of cells, but also includes the aging of the body as a whole. Studies have shown that aging can affect osteoimmune function through various mechanisms such as affecting the bone marrow microenvironment, causing immune cell...

Aging is a multifactorial process characterized by cellular dysfunction and increased susceptibility to age-related diseases. The interplay between autophagy and inflammasome has emerged as a critical factor influencing the aging process. Autophagy, which is responsible for degrading damaged cellular components, declines with age, leading to the accumulation of dysfunctional organelles and misfolded proteins. At the same time, the inflammasome, a key mediator of inflammatory responses, becomes...

OBJECTIVES: Investigate whether engaging in cognitive and physical activity is associated with cognitive performance and gray matter volume. Specifically, this study investigated the role of both activity types performed in close temporal proximity to each other.

Low back pain (LBP), primarily driven by intervertebral disc degeneration (IVDD), has become a core challenge in public health. DDX1, an RNA-binding protein, plays key roles in RNA metabolism but its function in IVDD remains unclear. We identify DDX1 as a substrate of methyltransferase EZH2, which methylates DDX1 at lysine 234 (K234), promoting IVDD in vitro and in vivo. EZH2 inhibition restores matrix homeostasis in nucleus pulposus (NP) cells and slows IVDD progression. Methylation at DDX1...

The autonomic nervous system (ANS) plays a pivotal role in regulating organ functions through descending brain-to-body signalling. The pathways involved are broadly categorized into two major branches: the sympathetic nervous system, which mediates 'fight or flight' responses, and the parasympathetic nervous system, which governs 'rest and digest' functions. Historically, the ANS was considered to mediate simple motor functions with limited neurochemical diversity. However, recent advances in...

CONCLUSION: The results indicate that clean energy use among older adults in China is regionally unbalanced and affected by various internal and external factors. Strategies to improve clean energy utilization among elderly adults in China should focus on rural areas with low socioeconomic levels and poorer health and living conditions.

CONCLUSIONS: Prolonged sitting time is significantly associated with accelerated aging, systemic immune-inflammation index and creatinine levels play important mediating roles in this process.

No abstract

B-1a cells, a self-renewing B cell subset essential for innate immunity, produce natural IgM antibodies that defend against pathogens, yet mechanisms sustaining their maintenance during aging remain unclear. We report that aging B-1a cells exhibit hallmarks of decline, including DNA damage, apoptosis, and reduced proliferation, with striking sex-specific disparities: aged females retain higher B-1a cell numbers than males, correlating with enhanced glycolysis and chromatin accessibility. Motif...