Immunosenescence, or immune system aging, has profound implications on infection susceptibility, vaccine efficacy, and immune resilience across the human lifespan. Despite extensive cross-sectional studies, little is known about how aging shapes CD8+ T cell subsets and their antigen-specific functionality in a longitudinal context. In this study, we employed a multi-omics approach integrating gene expression, surface proteomics, and TCR sequencing to characterize immunosenescence. CD8+ T cells were isolated from three individuals ranging from age 37 to 85. RNA-seq and CITE-seq data were integrated using a weighted nearest neighbors (WNN) approach to identify 12 functionally distinct CD8+ T cell subsets. Age-related upregulation of exhaustion markers (e.g., PD-1, KLRG1) and downregulation of key effector cytokine pathways (e.g., IFN-γ, TNF-α) were subset-specific. Comparisons between rare and hyperexpanded antigen-experienced clonotypes highlighted a trade-off between cytotoxicity and long-term maintenance. Public HCMV- and public influenza-specific clonotypes were identified and exhibited similar aging-associated dysfunction. These results suggest chronic inflammation (inflammaging) compromises CD8+ T cell function regardless of antigen-specificity. We highlight the TCF7 gene as the strongest potential candidate for immune system “rejuvenation.” Our findings underscore the importance of targeted interventions to address immune decline in aging populations to improve vaccine efficacy and infectious disease outcomes in older populations.

Disease susceptibility in bat colonies is an increasing concern, particularly following the recent global SARS-CoV-2 pandemic, and repeated spillover events. Despite extensive research, the factors influencing viral circulation within bat populations are under-investigated. This study aimed to investigate how sex, seasonality, and age structure the serological patterns of Henipavirus exposure in a captive population of Eidolon helvum bats in Ghana over a nine-year period. Longitudinal serological data were analyzed using statistical approaches including mixture models, t-tests, ANOVA, generalized additive mixed models (GAMMs), and a basic susceptible-infected-recovered (SIR) model to evaluate antibody dynamics and transmission trends. Results indicated that female bats maintained consistently higher Nipah virus antibody levels than males, particularly during the breeding season, suggesting a potential link between reproductive physiology and viral maintenance. Age-related patterns were less clear, likely due to sampling limitations. A simple SIR model captured basic serological trends but failed to fully replicate observed fluctuations, highlighting the need for more biologically complex models. These findings emphasize the importance of sex and seasonality in bat viral ecology, and contribute to improving our understanding of zoonotic transmission risk, which is critical for informing targeted surveillance and intervention strategies.