Aging & Longevity

Aging restricts maturation of CXCL13(+) T follicular helper cells in human immunity

20 hours 9 minutes ago
A decline in specific antibody responses is a hallmark of human aging, yet the differential contributions of B and T lymphocytes remain unclear. CXCL13 is a chemokine that shapes germinal center (GC) organization, but the regulation of human-specific CXCL13^(+) T follicular helper (Tfh) cells during aging is not known. Using human tonsil organoids, single-cell RNA sequencing, and CRISPR perturbations, we mapped age-associated changes in Tfh cells, the cell type that provides help to B cells in...
Nathan A Bracey

Socially shared emotions shape the activity of the medial prefrontal cortex during inference of others' emotional states

20 hours 9 minutes ago
The medial prefrontal cortex (mPFC) weighs options during decision-making, but its role in inferring competing emotional states and how this process changes with age, remain unclear. We recorded brain activity with functional MRI while 20 young and 40 older adults inferred the emotions of actors shown in ecological yet controlled social interactions. Socially shared representations about the timing, accuracy, and uncertainty of emotional inferences were defined using response distributions from...
Marine Le Petit

Genome integrity, somatic mutation, and the N-of-1 imperative in aging research

20 hours 9 minutes ago
Aging research has made remarkable progress in describing aging through the genetic architecture of longevity, epigenetic clocks, proteomic signatures, and systems-level analyses. Yet a critical dimension remains underrepresented: the role of genome integrity, germline and somatic mutation accumulation in individual-specific vulnerability, frailty, and multimorbidity across the life course. The need for individual-level thinking has deep roots, from Darwin's emphasis on individual variation in...
Diddahally R Govindaraju

Barriers and facilitators to physical activity among older Chinese adults in the UK: a qualitative descriptive study

20 hours 9 minutes ago
CONCLUSIONS: Older Chinese adults in the UK exhibit diverse PA patterns and face a range of barriers, underscoring the need to consider their varied needs and experiences when designing interventions. Factors influencing PA engagement align with the COM-B framework, highlighting the importance of addressing capability, opportunity, and motivation. These findings provide a practical evidence base to inform behaviour change interventions, supporting the development of culturally tailored...
Yang Yang

Vascular Immune Remodeling: A CD4<sup>+</sup> T Cell-Driven Immune Trajectory Associated With Arterial Stiffness

20 hours 9 minutes ago
Arterial stiffness is a hallmark of vascular aging and a major risk factor for cardiovascular disease. While immune aging-typically characterized by reduced T cell receptor (TCR) diversity and CD8^(+) memory expansion-contributes to this process, growing evidence suggests that peripheral immune dysregulation may impair vascular function through mechanisms distinct from classical immunosenescence. To investigate this, we profiled peripheral TCRβ repertoires from 563 adults without clinically...
Yu Miao

Diffusional aging at water/oil interfaces laden with charged nanoparticles studied by single-molecule tracking

1 day 20 hours ago
The adsorption of charged nanoparticles at water-oil interfaces constitutes a fundamental phenomenon, underlying pivotal technologies spanning from emulsion stabilization to the sophisticated fabrication of foams. However, the diffusional behavior of these nanoparticles remains poorly understood. Here, we use single-molecule tracking experiments to show that the diffusion of like-charged nanoparticles at the water-oil interface not only becomes anomalous but also displays a diffusional aging...
Yuehua Zhao

Multisystem predictors of dynamic gait stability across fall risk in older adults

1 day 20 hours ago
Gait stability arises from interactions between physiological, cognitive, and psychological systems, yet these domains are often assessed in isolation. This study examined multisystem predictors of anteroposterior margin of stability during walking (MoS(AP)) in community-dwelling older adults. Of 340 participants, 143 were retained after data quality screening (105 females; age: 70.8 ± 7.8 years). Participants completed the Physiological Profile Assessment (PPA), cognitive testing using Montreal...
Ashwini Kulkarni

Genetic architecture of white matter microstructure captured by unsupervised deep representation learning of fractional anisotropy maps

1 day 20 hours ago
Fractional anisotropy (FA) from diffusion MRI is a widely used marker of white matter (WM) integrity, but conventional FA-based genetic studies typically rely on tract- or atlas-defined averages that may obscure spatially distributed WM variation and limit genetic discovery. Here, we propose a deep learning framework, termed unsupervised deep representation of WM (UDR-WM), which uses voxel-wise FA maps to derive brain-wide unsupervised deep imaging phenotypes (UDIP-FA) without prior anatomical...
Xingzhong Zhao

LKB1 inactivation elicits an NNMT-mediated methyl sink and confers dependence on PRMT5 in lung cancer

1 day 20 hours ago
The protein arginine methyl transferase 5 (PRMT5) emerges as a therapeutic target in S-methyl-5'-thioadenosine phosphorylase (MTAP)-deleted cancers, where 5'-methylthioadenosine (MTA) accumulation partially inhibits its activity. However, it remains unclear whether other genetic alterations can dictate PRMT5 activity in cancer. Here, we identify liver kinase B1 (LKB1) as an alternative predictor of PRMT5 inhibition in lung cancer independent of MTAP. Mechanistically, LKB1 loss activates...
Wen Mi

Post-traumatic stress disorder moderates the association between BrainAge acceleration and GrimAge acceleration

1 day 20 hours ago
Individuals with post-traumatic stress disorder (PTSD) are at higher risk for age-related physical comorbidities, such as cardiovascular disorders, and exhibit accelerated epigenetic and brain aging. The present study examined PTSD as a moderator of the association between DNA methylation (DNAm)-based systemic aging (GrimAge, PhenoAge) and brain aging, indexed by MRI-based and DNAm-derived BrainAge estimates, in 174 lifetime PTSD cases and 138 trauma-exposed controls from four cohorts....
Jenna Beakas

The effect of a complex intervention for older adults on medication adequacy: results from the + AGIL Barcelona program

1 day 20 hours ago
CONCLUSIONS: While the + AGIL Barcelona program had a limited quantitative impact on polypharmacy, it significantly reduced PIMs' use, particularly in nervous system-acting medications, which are involved in increased risk of falling and cognitive impairment in older adults. The study highlights the importance of medication review in multidimensional frailty management, although future research with larger samples and standardized medication review protocols is needed.
Francesco Salis

Factors associated with the engagement in meaningful activity and occupational balance in institutionalised older adults: a prospective observational cohort study

1 day 20 hours ago
CONCLUSIONS: These findings underscore the need to review the type and range of activities offered in institutional settings, reducing time devoted to highly structured leisure activities and promoting more enriching experiences. To do so, experience-based co-design approaches involving institutionalised older adults and professionals in these settings are essential to develop person-centred programmes to enhance engagement in meaningful activities and occupational balance. Future research...
Rafael Prieto-Moreno

Intracellular mitochondrial-subcellular communication: A regulator of myocardial energy metabolic homeostasis in heart failure

2 days 20 hours ago
Heart failure (HF) is characterized by a severe disruption of myocardial energy metabolism, with mitochondrial dysfunction standing as a central pathological feature. However, the upstream regulatory mechanisms that drive metabolic remodeling, particularly across distinct HF phenotypes, remain inadequately defined. Mounting evidence reveals that, beyond their metabolic role, mitochondria act as central signaling hubs. This review proposes that dysfunctional mitochondrial-organelle crosstalk is a...
Yu-Xin Kang

Peripheral immunosenescence biomarkers and longitudinal cognitive decline: a large population-based study

2 days 20 hours ago
Peripheral immunosenescence has been increasingly implicated in dementia pathogenesis. However, the contributions of specific lymphocyte subsets to cognitive outcomes remain poorly defined, and evidence from large-scale longitudinal studies is scarce. We leveraged data from the US Health and Retirement Study (n = 7444; mean age: 67.7 ± 9.7 years). Our primary analysis calculated three ratio metrics to quantify T-cell immunosenescence: the CD4:CD8 ratio, CD4 + EMRA: Naïve and CD8 + EMRA: Naïve...
Rong Hua

Reductive death is averted by a conserved de novo lipogenic switch

2 days 20 hours ago
Biguanides, including metformin, the world's most prescribed oral hypoglycemic, extend health span and lifespan in vertebrates and invertebrates. Given the widespread use and apparent safety of metformin, it is assumed that its effects are not associated with toxicity, except when in marked excess. Here, we determine that accumulation of damaging reducing equivalents is an unanticipated toxicity associated with biguanides, defense against which requires post-transcriptional protection of de novo...
Fasih M Ahsan
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2 hours 29 minutes ago
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