Epigenetic clock and methylation studies in the rhesus macaque

Area of Science:

• Epigenetics and aging research
• Mammalian genomics
• Primate biology

Background:

• Epigenetic clocks, based on DNA methylation, accurately estimate chronological age in various species.
• While generally species-specific, the underlying principles of epigenetic clocks are conserved across mammals.
• Rhesus macaques are crucial models in biomedical research, necessitating species-specific aging biomarkers.

Purpose of the Study:

• To develop and validate novel epigenetic clocks for the rhesus macaque (Macaca mulatta).
• To assess the applicability of these clocks across different tissue types and species (human-macaque).
• To explore the potential of epigenetic clocks in understanding primate aging and age-related conditions.

Main Methods:

• Profiling DNA methylation using a custom array (HorvathMammalMethylChip40) in 281 tissue samples from rhesus macaques.
• Generating five distinct epigenetic clocks tailored for macaques, including pan-tissue, blood, and skin-specific models.
• Evaluating cross-species applicability (human-macaque) and correlation with other primate species (vervet monkey).

Main Results:

• Five epigenetic clocks for macaques were successfully generated, demonstrating applicability across various tissues (blood, skin, adipose, kidney, liver, lung, muscle, cerebral cortex).
• A human-macaque epigenetic clock showed high age correlation (R=0.89) with vervet monkeys.
• Four specific CpGs in the KLF14 promoter consistently changed with age across four tissues.

Conclusions:

• Developed epigenetic clocks provide reliable tools for estimating chronological age in rhesus macaques.
• These clocks can be applied across multiple tissues and potentially bridge human and macaque aging research.
• Further research is warranted to investigate the predictive power of these epigenetic clocks for age-related diseases in macaques.