Unraveling Brain Structural Correlates of Cognitive Aging and Resilience in Long-Lived Bats: An Integrated Study of Epigenetic Age and Spatial Memory

Abstract: Understanding the neural basis of cognitive aging and resilience, particularly in exceptionally long-lived species like the Egyptian fruit bat that resist typical age-related pathologies, is crucial for unraveling mechanisms of healthy longevity. Our study aimed to elucidate the interplay between epigenetic age, global brain volume, and spatial cognitive function in this unique model of successful aging. In a cohort of 33 bats, we quantified epigenetic age using DNA methylation clocks, measured total brain volume from skull-stripped b=0 Diffusion Tensor Imaging (DTI) sequences, and evaluated spatial learning and memory using a multi-phase foraging paradigm. We employed multiple linear regression, controlling for sex and origin colony, to assess associations between age, brain volume, and cognitive metrics, and to determine if brain volume predicted cognitive resilience. Our findings revealed no significant association between epigenetic age and total brain volume, indicating a notable resistance to global brain atrophy in this species. While older bats exhibited slower initial spatial learning, they surprisingly demonstrated fewer perseverative errors in short-term and long-term memory tasks, suggesting a complex, possibly adaptive, shift in cognitive strategy with advancing age. Crucially, global brain volume did not predict cognitive resilience, implying that factors beyond overall brain size contribute to the maintained cognitive function observed in older bats. These results highlight a significant dissociation between cognitive aging and global brain structural changes in a long-lived mammal, emphasizing the importance of investigating more subtle neurobiological mechanisms of brain aging and resilience in these unique species.

Subjects:	q-bio.NC; q-bio.QM
Cite as:	PX:2508.00033