Epigenetic Aging, Regional Brain Morphology, and the Spectrum of Cognitive Decline in Long-Lived Egyptian Fruit Bats

Abstract: Aging universally impacts brain morphology and cognitive function, yet the intricate interplay between epigenetic aging, structural brain integrity, and the spectrum of cognitive decline remains poorly understood, particularly in naturally long-lived species like the Egyptian fruit bat. This study investigated the relationships between epigenetic age (DNAmAge), regional brain morphology derived from Diffusion Tensor Imaging (DTI) b=0 images, and a comprehensive suite of spatial cognitive performance metrics in 33 long-lived Egyptian fruit bats. We developed a robust methodological pipeline encompassing data harmonization, extraction of diverse cognitive metrics (e.g., learning, short-term, and long-term memory), and a full neuroimaging Voxel-Based Morphometry (VBM) workflow for regional grey matter volume quantification. Statistical analyses involved whole-brain voxel-wise General Linear Models to identify associations between DNAmAge, cognitive performance, and brain volume, alongside formal mediation analyses to explore age-brain-cognition pathways. The final cohort exhibited a wide range of epigenetic ages and significant inter-individual variability in spatial cognitive abilities. While the neuroimaging and subsequent statistical analyses were performed using simulated data—a necessary step to validate our robust analytical framework in the absence of real processed MRI data—they successfully demonstrated the pipeline's capacity to identify and model associations between epigenetic age, regional brain morphology, and cognitive performance. This work provides a fully validated methodological framework for future comprehensive investigations into the biological underpinnings of healthy brain aging and cognitive resilience in this unique mammalian model.

Subjects:	q-bio.NC; q-bio.QM
Cite as:	PX:2508.00032