UCLA

Epigenetic clocks, DNA methylation-based biomarkers, accurately measure age withinspecific species and tissues but face challenges in multi-species and non-mammalian contexts. This study aims to enhance the construction of biologically meaningful, multi-species epigenetic clocks, particularly applicable to both humans and animals. Utilizing supervised machine learning on DNA methylation data, this research incorporates biological information, such as genome mapping and life history traits, to improve clock accuracy and interpretability. Findings include the development of diverse epigenetic clocks for various mammalian species, enabled by robust statistical methods and a reproducible software pipeline. An R package, MammalMethylClock, was introduced to facilitate the construction, assessment, and application of these clocks, incorporating existing models from the Mammalian Methylation Consortium. This package supports translational biomedical research by enhancing the study of age-related chronic diseases across different model organisms. Moreover, the remainder of this study examines the research problem of accelerated aging in people living with HIV (PLWH) and the mitigating effects of highly active antiretroviral therapy (HAART). Previous research indicates that HIV-related age acceleration begins shortly after seroconversion. This longitudinal study within the Multicenter AIDS Cohort Study (MACS) examines 60 PLWH and 60 matched controls across four specific time points: pre- seroconversion, closest to seroconversion, pre-HAART, and post-1-3 years of HAART. The study uses comprehensive epigenetic clock data and flow cytometry measures, including naive, senescent, activated, and total CD4/CD8 counts. The method involves analyzing epigenetic aging through five different aging clocks at these time points to assess the impact of HIV on aging and the partial restoration effects of HAART on immune function and aging patterns. By tracking these changes, the study aims to identify specific aging patterns associated with HIV and guide potential interventions. The findings reveal that HIV infection significantly accelerates epigenetic aging in most clocks, and this acceleration is only partially mitigated by HAART. This suggests that HIV contributes to the premature onset of clinical aging through its profound effects on the immune system, even when viral replication is controlled. The study underscores the need for interventions to enhance the healthspan of PLWH and offers insights into the broader aging process.