Aging & Longevity
An OpIE2-DsRed marker disrupts female blood-feeding and shortens lifespan in the malaria vector Anopheles gambiae
Anopheles gambiae is one of the principal vectors of human malaria. Over the past two decades, transgenic mosquito strains have been essential tools for studying mosquito biology and developing genetic control strategies such as gene drives. Mosquito transformants are typically identified using fluorescent markers, which are assumed to be phenotypically neutral. While generating CRISPR-based gene drive strains carrying an OpIE2-DsRed marker we unexpectedly found that transgenic females were...
APOE ε4 and Decline in Health and Financial Literacy in Advanced Age
CONCLUSIONS: ε4 contributes to literacy decline among older adults, presumably due in part to the accumulation of neuropathologies associated with ε4. We discuss the potential clinical implications of ε4-related literacy decline.
Development and Feasibility of PATH: Preparation for Appropriate Transitions From Home
CONCLUSIONS: A decision support tool for caregivers of PLwD that provides education about transitions in care site, along with support for the emotional aspects of decision making, is highly acceptable and supports caregivers' ability to engage with what can be a challenging topic.
Resting-state EEG aperiodic exponent moderates the association between age and memory performance in older adults
Memory functions are susceptible to age-related cognitive decline, making it essential to explore the underlying neurophysiological mechanisms that contribute to memory function during healthy ageing. Resting-state EEG (rsEEG) parameters, particularly the aperiodic exponent, a marker of cortical excitation-inhibition balance, and individual alpha peak frequency, a correlate of neural processing efficiency, have demonstrated associations with ageing and cognitive functions. This study...
Unraveling sex differences in age-related hippocampal decline: differential mitochondrial dysfunction, Lonp1-dependent mitochondrial proteostasis and mtROS production in aged C57BL/6 mice
Aging is a progressive process characterized by cellular and molecular damage leading to mitochondrial dysfunction and cognitive decline. Mitochondrial dysfunction is a critical factor in memory impairment in aging and neurodegenerative diseases. While sex differences in aging have been observed across various species, the underlying cellular and molecular mechanisms remain poorly understood, mainly focused on mitochondrial proteostasis. This study examined hippocampal-dependent cognitive...
How do the oldest old die in very fast ageing territories? The case of overseas France
CONCLUSIONS: The population of nonagenarians was specific in causes of death and comorbidities. Improving end-of-life care for these patients can include a high access to specialist palliative care and symptoms management.
Chemotherapy-induced adipo-lineage cell senescence drives bone loss
Chemotherapy-induced bone loss is a debilitating and common side effect of cancer treatment, though its underlying mechanisms remain poorly understood. Here, we show that, despite the systemic administration of chemotherapy, cellular senescence is restricted to bone marrow adipo-lineage cells specifically Cxcl12-abundant reticular (CAR) cells and bone marrow adipocytes (BMAds). Induction of senescence within these populations promotes RANK ligand (RANKL)-mediated osteoclastogenesis, leading to...
Multiscale mitochondrial cristae remodeling links Opa1 downregulation to reduced OXPHOS capacity in aged hearts
Aging is closely associated with cardiovascular diseases, the leading cause of mortality worldwide. Mitochondrial dysfunction is a hallmark of cardiovascular aging. Most of the heart's ATP is produced at the cristae, specialized subcompartments where oxidative phosphorylation (OXPHOS) takes place. In this study, we used multiple-scale electron microscopy approaches to evaluate age-related mitochondrial and ultrastructural alterations of cristae in human and mouse hearts. We found that aged...
Charting brain morphology in international healthy and neurological populations
Quantifying individual deviations in brain morphology from normative references is useful for understanding neurodiversity and facilitating personalized management of brain health. Here we report Chinese brain normative references using morphological imaging scans of 24,061 healthy volunteers from 105 sites, revealing later peak ages of lifespan neurodevelopmental milestones (1.2-8.9 years) than European/North American populations. We model individual brain deviation scores in 3,932 individuals...
Proactive health management strategies for older adults with motoric cognitive risk syndrome: a scoping review
CONCLUSIONS: Current research on MCR management is in its early stages and does not fully align with the integrated, proactive principles of the PHM framework. The evidence base is dominated by risk stratification and preliminary intervention studies, while foundational areas like health literacy and technological monitoring are less developed. Future work could focus on standardizing MCR assessment, addressing key gaps in the underrepresented PHM dimensions, and developing and testing...
Senolytic Treatment With Dasatinib and Quercetin Reshapes Influenza-Specific CD8 T Cell Responses During Infection in Aged, Vaccinated Mice
Older adults are disproportionately affected by infectious diseases like influenza (flu) due to immune declines and poor vaccine responses. Senolytics have been shown to improve various age-related conditions and positively influence infection outcomes, yet their potential to enhance vaccine responses has not yet been explored. Here, we evaluated the potential of senolytic combination Dasatinib (D) and Quercetin (Q) treatment prior to influenza vaccination to potentiate immune responses in aged...
Senolytic-Resistant Senescent Cells Have a Distinct SASP Profile and Functional Impact: The Path to Developing Senosensitizers
The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30%-70% of SCs, act by transiently disabling the senescent cell antiapoptotic pathways (SCAPs), which defend those SCs that are proapoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human...
Parental kinship influences global methylation and epigenetic age estimation in Peromyscus
Kinship relationships between parents affect offspring fitness. Beyond its effects in heterozygosity or its impact in deleterious alleles that can be reduced to homozygosity and decrease the individuals' fitness, the consequences of parental relatedness in the offspring remain understudied. By leveraging the availability of detailed pedigrees of captive Peromyscus we explored how parental relatedness impacts the methylome and the epigenetic age estimation of the offspring. Global CpG methylation...
The Right Person, the Right Treatment, at the Right Time in Alzheimer's Disease: Insights From the 2025 Brain Aging Symposium
On October 22nd, 2025, Brain Aging Symposium took place at Harvard Medical School bringing together leading researchers from academia and partner organizations to discuss recent advances in measuring and monitoring human brain aging trajectories, with a particular focus on Alzheimer's disease (AD). A central theme emerged: achieving "the right treatment for the right person and the right time" through precision medicine approaches. Key advances included the unprecedented validation of...
Loss of p62 Binding Allows TIF-IA Accumulation in Senescence, Which Promotes Phenotypic Changes to Nucleoli and the Senescence Associated Secretory Phenotype
A key characteristic of senescent and ageing cells is a reduction in number and increase in size of nucleoli. Although a number of pathways have been suggested, the mechanisms underlying this altered nucleolar phenotype, and the downstream consequences, remain poorly understood. The PolI complex component, TIF-IA, has previously been implicated in regulating this characteristic nucleolar phenotype in response to stress. Here we explored the role of TIF-IA in senescence and ageing. We show that...
Taxonomic and functional signatures of smoking and periodontitis severity in the subgingival microbiome of older adults
Periodontitis and smoking are major contributors to oral and systemic health deterioration in aging adults. This study investigated the combined effects of smoking status and periodontitis severity on the subgingival microbiome in 1107 individuals aged 69-72 using shotgun metagenomic sequencing. Smoking was linked to reduced microbial diversity, enrichment of periodontal pathogens, and depletion of health-associated commensals, while increasing periodontitis severity was associated with broader...
IL-17a induces age-related olfactory dysfunction by impairing regeneration and promoting respiratory metaplasia in mice
The olfactory epithelium (OE) undergoes life-long renewal and regeneration. This process is supported by the globose basal cells (GBC) during the homeostatic state, as well as horizontal basal cells (HBC) during severe damage. Inflamm-aging refers to the low-grade, chronic and progressive state of heightened pro-inflammation associated with aging. However, the impact of inflamm-aging on OE homeostasis, regeneration, and the inflammatory microenvironment is not fully understood. In this study...
Plasma proteomic signatures of social support and their association with cardiovascular disease and mortality: exploratory analyses in a national cohort study
Social support has been related to cardiovascular disease (CVD) incidence and mortality in longitudinal cohort analyses, but the biological pathways underpinning this remain underexplored. This exploratory study examined the associations between social support and a wide range of proteomic biomarkers and performed the mediating effect of proteomic biomarkers in the association between social support and CVD and mortality to identify potential biological pathways linking social support to health...
Self-Organizing Ovarian Somatic Organoids Preserve Cellular Heterogeneity and Reveal Cellular Contributions to Ovarian Aging
Ovarian somatic cells are essential for reproductive function, but no existing ex vivo models recapitulate the cellular heterogeneity or interactions within this compartment. We engineered an ovarian somatic organoid model by culturing a stroma-enriched fraction of mouse ovaries in scaffold-free agarose micromolds. Self-organized ovarian somatic organoids maintained diverse cell populations, produced extracellular matrix, and secreted hormones. Organoids generated from reproductively old mice...
Body roundness index and mortality risk in chronic diseases: a national prospective longitudinal study in China
CONCLUSIONS: BRI is a multifaceted predictor of chronic disease mortality, with associations varying by disease pathophysiology and population characteristics. It offers a pragmatic tool for refining risk stratification in aging populations and challenges one-size-fits-all approaches to obesity management. Future research should investigate dynamic BRI trajectories and interactions with disease-specific biomarkers.
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