Decoding immune aging: alternative splicing in T cells

The immune system's gradual decline with age, known as immune aging, increases susceptibility to infections, autoimmune diseases, and cancers. T cells, crucial for adaptive immunity, undergo significant changes in number and function over time. Previous studies have focused on age-related alterations in T cell populations and gene expression, but the role of alternative splicing remains unclear. Based on these challenges, it is essential to conduct in-depth research on the alternative splicing events in T cells to better understand and potentially mitigate immune aging.

Researchers from Jinan University, China, have published a study (DOI: 10.26599/AGR.2023.9340007) on 29 May 2024, in the journal Aging Research, exploring age-related alternative splicing in human T cells. The study presents a detailed analysis of splicing events across 13 T cell subtypes from young and old individuals, identifying numerous age-related changes. By constructing an atlas of these splicing events, the researchers aim to uncover the molecular mechanisms underlying immune aging and suggest potential therapeutic targets for enhancing immune function in the elderly.

The study analyzed RNA-seq data from 205 samples of 13 distinct T cell subtypes from both young (20-30 years) and old (over 65 years) individuals. Researchers identified differential splicing events (DSEs) that occur more frequently in specific T cell subtypes, such as effector and tissue-resident memory T cells, with aging. Key genes like PDCD4 and ARCN1, involved in T cell activation and apoptosis, showed significant age-related splicing changes. The findings reveal that aging primarily affects pathways related to RNA splicing, immune response regulation, and T cell differentiation. By highlighting the unique splicing profiles of different T cell subtypes, this research underscores the complexity of immune aging and its impact on immune functionality. The splicing atlas created in this study serves as a valuable resource for understanding post-transcriptional regulation in T cells and opens new avenues for developing therapies to mitigate the effects of aging on the immune system.

Dr. Oscar Junhong Luo, a senior researcher involved in the study, comments, "Our findings shed light on the intricate changes in T cell functionality driven by alternative splicing as we age. This detailed splicing atlas opens up new possibilities for understanding immune aging and developing targeted therapies to enhance immune resilience in the elderly. The identification of key genes involved in age-related splicing changes presents exciting opportunities for future research and therapeutic interventions."

The study's insights into alternative splicing in T cells pave the way for innovative approaches to address immune aging. Potential applications include the development of targeted therapies aimed at modulating splicing events to enhance T cell function in the elderly. These interventions could improve resistance to infections, reduce the incidence of autoimmune diseases, and enhance overall immune health. Furthermore, the comprehensive splicing atlas serves as a valuable resource for researchers exploring the molecular underpinnings of immune aging, potentially leading to breakthroughs in age-related disease prevention and treatment.

This work was supported by grants from the Natural Science Foundation of China (No. 32050410285 to O.J.L.); the Guangzhou Planned Project of Science and Technology (No. 202002020039 to O.J.L.); the Pearl River Talents Scheme of Guangdong Province (No. 2019QN01Y990 to O.J.L.); and the Initial Startup Fund of Jinan University (O.J.L.).

About Aging Research

Aging Research is a peer-reviewed, Open Access publication sponsored by Jinan University and published by Tsinghua University Press. It publishes original research in all areas of aging, longevity, aging related diseases and health issues, specifically accepting the results of unusual significance or broad conceptual or technical advances, particularly the innovative phenotypic reporting without relevant mechanisms, innovative clinical case reports and studies with negative results. Aging Research aims to foster interactions among different areas of this diverse field of research and to promote new and exciting ideas within and beyond the research community, to enable synergy and maximize scientific and societal impact.

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