Journal Article

Pathogenic SIV infection is associated with acceleration of epigenetic age in rhesus macaques

He, Tianyu, Xu, Cuiling, Brocca-Cofano, Egidio, Milčiūtė, Milda, Sivanandham, Sindhuja, Nayak, Krishna, Ma, Dongzhu, Sivanandham, Ranjit, Brooke, Robert T., Jasinska, Anna J., Policicchio, Benjamin B., Pandrea, Ivona, Ribeiro, Ruy M., Annapureddy, Haritha, Sette, Paola, Talwar, Saharsh, Gordevicius, Juozas, Apetrei, Cristian

2025

Overview

HIV infection accelerates biological aging, but the contribution of the host's age to this process is unknown. We investigated the influence of SIV infection in macaques (SIVmac) on the risk of comorbidities and aging in young and old rhesus macaques (RMs) by assessing pathogenesis markers, DNA methylation-based epigenetic age (EA), and EA acceleration (EAA) in blood and tissues. Initially, upon SIV infection, the young RMs showed greater resilience to CD4+ T cell depletion, better control of T cell activation, hypercoagulation, and excessive inflammation, yet this resilience was progressively lost in the advanced stages of infection. During the late stages of infection, the young RMs, but not the aged ones, showed an increase in EA in PBMCs; also, EAA in the cerebellum and heart of young RMs was higher compared with old RMs. SIV infection was more pathogenic in aged animals in early stages, leading to a more rapid disease progression; however, accelerated aging mostly affected young animals, so that the levels of multiple key pathogenesis markers in the young RMs converged toward those specific to aged ones in the late stages of infection. We conclude that SIV infection-driven age acceleration is tissue specific, and that host age influences the susceptibility of different tissues to enhanced aging.

• Publisher: American Society for Clinical Investigation
• Subject: Acquired immune deficiency syndrome / Age / Age factors in disease / Aging / Aging - genetics / Aging - immunology / Aging - pathology / AIDS / AIDS/HIV / Animals / Brain / CD4 antigen / CD4-Positive T-Lymphocytes - immunology / CD4-Positive T-Lymphocytes - pathology / Cell activation / Cerebellum / Chronic illnesses / Comorbidity / Disease / DNA Methylation / Epigenesis, Genetic / Epigenetics / Gene expression / Genetic aspects / Health aspects / HIV / Human immunodeficiency virus / Infections / Infectious disease / Inflammation / Life expectancy / Lymphocytes / Lymphocytes T / Macaca mulatta / Male / Mortality / Older people / Pathogenesis / Plasma / Senescence / Simian Acquired Immunodeficiency Syndrome - genetics / Simian Acquired Immunodeficiency Syndrome - immunology / Simian Acquired Immunodeficiency Syndrome - pathology / Simian immunodeficiency virus / Simian Immunodeficiency Virus - immunology / Virulence (Microbiology)