Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samples
This study aimed to identify age-related genes and alternative splicing (AS) events by comprehensive transcriptome analysis of 1,255 healthy blood samples from individuals aged 8–87 years. We identified 1,029 up-regulated and 1,186 down-regulated genes in older individuals, including 17 genes overla...
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| Language: | English |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Aging |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fragi.2025.1575862/full |
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| author | Shuhan Li Shuhan Li Haohao Lv Haohao Lv Renxin Zhang Renxin Zhang Jinjun Li Jinjun Li Zhiyuan Chen Zhiyuan Chen Naixue Yang Naixue Yang Shaoxing Dai Shaoxing Dai |
| author_facet | Shuhan Li Shuhan Li Haohao Lv Haohao Lv Renxin Zhang Renxin Zhang Jinjun Li Jinjun Li Zhiyuan Chen Zhiyuan Chen Naixue Yang Naixue Yang Shaoxing Dai Shaoxing Dai |
| author_sort | Shuhan Li |
| collection | DOAJ |
| description | This study aimed to identify age-related genes and alternative splicing (AS) events by comprehensive transcriptome analysis of 1,255 healthy blood samples from individuals aged 8–87 years. We identified 1,029 up-regulated and 1,186 down-regulated genes in older individuals, including 17 genes overlapped with known aging-associated genes, such as TFAP2A and Klotho. Gene set enrichment analysis revealed significant alterations in immunoregulatory and metabolic pathways during aging. However, many senescence-associated secretory phenotypes (SASP) involved genes did not exhibit changes in gene expression, suggesting that AS events may reveal additional age-related mechanisms. Aging also altered 6,320 AS events in 4,566 genes, impacting immune-related protein domains. The RNA-binding protein RBMS3 emerged as a key regulator of aging-specific AS events. In addition, neoantigen prediction analyses further identified potential neoantigens generated by aging-related AS events, with the HLA-C14:02 allele presenting the most neoantigenic peptides. Notably, 60 neoantigenic peptides were confirmed using proteomic data from elderly individuals, suggesting their potential as novel targets for anti-aging immunotherapy. Our study provides new insights into the role of alternative splicing in aging, highlights promising avenues for anti-aging immunotherapy. |
| format | Article |
| id | doaj-art-cfa545ccb9da4fb89d2c58ca0555d50a |
| institution | Kabale University |
| issn | 2673-6217 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging |
| spelling | doaj-art-cfa545ccb9da4fb89d2c58ca0555d50a2025-08-20T03:53:06ZengFrontiers Media S.A.Frontiers in Aging2673-62172025-05-01610.3389/fragi.2025.15758621575862Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samplesShuhan Li0Shuhan Li1Haohao Lv2Haohao Lv3Renxin Zhang4Renxin Zhang5Jinjun Li6Jinjun Li7Zhiyuan Chen8Zhiyuan Chen9Naixue Yang10Naixue Yang11Shaoxing Dai12Shaoxing Dai13State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, ChinaYunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, ChinaYunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, ChinaYunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, ChinaYunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, ChinaYunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, ChinaYunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, ChinaState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, ChinaYunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, ChinaThis study aimed to identify age-related genes and alternative splicing (AS) events by comprehensive transcriptome analysis of 1,255 healthy blood samples from individuals aged 8–87 years. We identified 1,029 up-regulated and 1,186 down-regulated genes in older individuals, including 17 genes overlapped with known aging-associated genes, such as TFAP2A and Klotho. Gene set enrichment analysis revealed significant alterations in immunoregulatory and metabolic pathways during aging. However, many senescence-associated secretory phenotypes (SASP) involved genes did not exhibit changes in gene expression, suggesting that AS events may reveal additional age-related mechanisms. Aging also altered 6,320 AS events in 4,566 genes, impacting immune-related protein domains. The RNA-binding protein RBMS3 emerged as a key regulator of aging-specific AS events. In addition, neoantigen prediction analyses further identified potential neoantigens generated by aging-related AS events, with the HLA-C14:02 allele presenting the most neoantigenic peptides. Notably, 60 neoantigenic peptides were confirmed using proteomic data from elderly individuals, suggesting their potential as novel targets for anti-aging immunotherapy. Our study provides new insights into the role of alternative splicing in aging, highlights promising avenues for anti-aging immunotherapy.https://www.frontiersin.org/articles/10.3389/fragi.2025.1575862/fullagingtranscriptome analysisalternative splicingimmunosenescenceneoantigensanti-aging immunotherapy |
| spellingShingle | Shuhan Li Shuhan Li Haohao Lv Haohao Lv Renxin Zhang Renxin Zhang Jinjun Li Jinjun Li Zhiyuan Chen Zhiyuan Chen Naixue Yang Naixue Yang Shaoxing Dai Shaoxing Dai Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samples Frontiers in Aging aging transcriptome analysis alternative splicing immunosenescence neoantigens anti-aging immunotherapy |
| title | Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samples |
| title_full | Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samples |
| title_fullStr | Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samples |
| title_full_unstemmed | Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samples |
| title_short | Aging-related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1,255 human blood samples |
| title_sort | aging related alternative splicing drive neoantigen emergence revealed by transcriptome analysis of 1 255 human blood samples |
| topic | aging transcriptome analysis alternative splicing immunosenescence neoantigens anti-aging immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fragi.2025.1575862/full |
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