Aging & Longevity

Trained immunity, an emerging treatment strategy, confers long-term anti-tumour memory by modulating epigenetic and metabolic reprogramming of innate immune cells, offering a novel pathway for immunotherapy of haematological malignancies. This article systematically outlines the mechanisms by which inducers such as β-glucan, Bacille Calmette-Guérin (BCG) and cytokines train key effector cells including macrophages and natural killer (NK) cells. It further analyses how ageing-encompassing both...

The human antiviral antibody reactome provides a cumulative molecular record of immune exposures. Using high-resolution VirScan profiling, we compared epitope-level antibody responses across early childhood and adulthood. Infants are born with maternal IgG antibodies, but these antibodies decay rapidly and are replaced by endogenous responses to ~22 new viral exposures within three years. Pediatric antibody reactivities remain highly dynamic until about age 7 and are broad in epitope specificity...

Nutrition shapes development, health and risk of disease over the life course and across generations. The predominant approaches to understanding these relationships have either been to consider the effects of single nutrients, one at a time, or to consider associations with food types and dietary patterns. Although, to date, the single-nutrient approach has defined much of the scientific enquiry and public debate on the macronutrients - carbohydrate, fat and protein - there is an emerging...

Biodiversity loss in the present era requires new tools for studying nonmodel organisms. Elephants are both an endangered species and excellent models for studying complex phenotypes including size, social behavior and longevity. Here we report the first derivation of elephant (Elephas maximus) induced pluripotent stem (emiPS) cells. We achieved emiPS cells using two approaches: (1) a two-step process of chemical media induction and colony selection followed by over-expression of elephant...

Incidence of early-onset cancer is rising globally in recent generations, which underscores the need to elucidate the influence of emerging generational risk factors. Systemic and organ-specific aging reflects the cumulative impact of exposures and may provide an integrative and complementary approach to understand early-onset cancer risk. Here among 154,169 young adults from the United Kingdom Biobank, systemic aging measured by PhenoAge increased across birth cohorts, with 23% s.d. increase...

Hepatic inflammation and immunosurveillance play major roles in the progression of liver cancer. A common trigger for hepatic inflammation is oxidative stress, which stems from mitochondrial dysfunction. Here, we demonstrate that deletion of the mitochondrial stress integrator OMA1 increases hepatic primary tumor incidence and impairs survival in mice. Persistent activation of the KEAP1-Nrf2 oxidative stress pathway in the absence of OMA1 promotes early liver injury, which progresses into...

The accumulation of aberrant proteins or their impaired clearance leads to neurodegenerative diseases (NDs). The protein amino terminus (Nt) and its modifications determine the fate of proteins and their cellular effects. Nt acetylation, Nt methylation, and Nt myristoylation are protein Nt modifications implicated in the pathogenesis of proteinopathies like Alzheimer's, Parkinson's, and Huntington's diseases by regulating the protein lifespan, folding, and interaction with protein/DNA. In...

Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) represent a promising cell-free strategy for intervertebral disc degeneration (IDD). Here, we obtained oxidative stress-preconditioned exosomes (O-Exos) from BMSCs exposed to low-concentration hydrogen peroxide. Compared with exosomes from untreated cells (N-Exos), O-Exos more effectively delayed nucleus pulposus (NP) cell senescence and attenuated IDD in vitro and in vivo. The superior effects of O-Exos were associated with...

Aging-related metabolic dysregulation and vascular vulnerability contribute substantially to stroke susceptibility, yet subtype-specific metabolic signatures remain incompletely characterized. Employing a nested case-control design within the Taizhou Longitudinal Study, we quantified 296 lipoprotein parameters and 54 metabolites in 1208 stroke-control pairs using nuclear magnetic resonance. Logistic regression estimated subtype-specific associations, and machine learning constructed prediction...

Resting heart rate (RHR) is an accessible measure that may reflect age-related cardiovascular and autonomic dysregulation relevant to cognitive ageing. However, evidence linking RHR with cognitive outcomes is inconsistent, and most studies relied on single baseline measurements that may not capture cumulative exposure. This study examined the associations of baseline and longitudinally averaged RHR with cognitive decline and dementia in older adults. This was a secondary analysis of the ASPirin...

CONCLUSION: In this exploratory randomized trial, JQG was associated with greater improvements in grip strength, physical performance, and sarcopenia-related quality of life than calcitriol over 12 weeks, with no major safety concerns observed. Exploratory biomarker and metabolomic findings suggest that inflammatory regulation, hormonal and neurotrophic modulation, and bile acid-related metabolic remodeling may be involved in the response to JQG. These findings are hypothesis-generating and...

CONCLUSIONS: Sarcopenia and even possible sarcopenia were associated with higher risks of incident ADL inability.

Social connectedness strongly influences health and longevity, and adult pair bonds provide psychological benefits distinct from other social relationships. Oxytocin (OT), corticotropin-releasing hormone (CRH), and opioids play an important role in pair bond formation and maintenance. OT modulates the stress response via the hypothalamic-pituitary-adrenal (HPA) axis, while the kappa (κ) opioid system may modulate OT signaling in contexts of stress and separation. Here, 20 male and female coppery...

Senescent cells accumulate in chronically diseased liver tissues and are known to actively contribute to disease pathology. To date, these studies have predominantly focussed on senescence in epithelial cells, such as hepatocytes and biliary epithelial cells, and senescence in liver endothelial cells remains largely understudied. Here, we utilise publicly available single-cell RNA-sequencing data, immunohistochemical and immunofluorescent staining to detect senescent endothelial cells within...

Aging is a progressive and irreversible biological process that contributes to the pathogenesis of numerous age-related diseases. Elucidating the molecular mechanisms of aging is crucial for promoting healthy aging and extending healthspan. RNA-binding proteins (RBPs) are pivotal regulators of post-transcriptional gene expression and play essential roles in diverse biological processes. RBPs interact with both coding and non-coding RNAs to regulate RNA metabolism, stability, localization, and...

Age acceleration, or the difference between biological and chronological age, is a research area of growing interest, particularly in the field of age-related and neurodegenerative disorders, including Alzheimer's disease (AD). First-generation epigenetic clocks that predict chronological age utilising DNA methylation data were the first to derive estimates of age acceleration, which have been associated with several age-related conditions. More recently, second-generation epigenetic clocks that...

Alzheimer's disease (AD) involves early disruptions in brain connectivity, yet how AD risk markers relate to resting-state dynamic functional connectivity (rs-dFC) remains unclear. We examined associations of AD pathology, genetic risk, and blood-based biomarkers (BBMs) of neurodegeneration with local and distant rs-dFC in cognitively normal older adults and explored links with cognitive performance. Baseline data from 86 cognitively normal older adults in the AGUEDA trial (NCT05186090) were...

Telomere length (TL) has been proposed as a marker of appendicular lean mass (ALM) decline; however, longitudinal evidence remains limited. We aimed to investigate the longitudinal association between TL and 6-year trajectories of ALM. This longitudinal study included 185 older adults aged 55-75 years with overweight or obesity and metabolic syndrome at baseline. Baseline TL was assessed using a monochrome multiplex real-time quantitative PCR. ALM from the four limbs was obtained at baseline,...

Immune checkpoint blockade (ICB) shows limited efficacy in pancreatic ductal adenocarcinoma (PDAC). Here, we demonstrate that ICB-induced IFN-γ signaling upregulates H2-T23 on pancreatic tumor cells, which interacts with NKG2A on NK cells to induce NK cell senescence through activation of p38 MAPK and STAT1/3 pathways. This impairs NK cell cytotoxicity and restricts antitumor immunity. Dual blockade of PD-1 and NKG2A effectively prevents NK cell senescence, restores NK cell function, and...

CONCLUSION: SSDH that shape dementia risk and brain resilience, many modifiable at the community and policy levels, remain unevenly collected in Canadian aging and dementia cohorts. Strengthening and harmonizing SSDH measurement is a critical step toward equitable dementia prevention and reducing health disparities.