Age is associated with alterations in sensation and cognition, but little is known of how sensory-cognitive interactions change over time, especially during late middle age. This project examined the change in relations between sensation and cognition and their consistency with established models of neurocognitive aging. Three studies examined associations between visual contrast sensitivity (CS), auditory pure tone acuity (PTA), and cognition among male twins from the Vietnam Era Twin Study of Aging (VETSA), who were assessed twice (VETSA 1, x̅𝑎𝑔𝑒 = 56, n =1,237, VETSA 2, x̅𝑎𝑔𝑒 = 62, n =1,016). Study 1 examined sensory relations, with the hypothesis of more and stronger correlations between CS and PTA at VETSA 2 than at VETSA 1 and a larger genetic correlation at VETSA 2 than at VETSA 1. Heritability at VETSA 1 and VETSA 2 was significant for multiple CS and PTA frequencies, and heritability increased with age. At VETSA 2, there were more shared genes between CS and PTA than at VETSA 1. Studies 2 and 3 examined sensory-cognitive associations. The Study 2 hypotheses of more and stronger associations between CS and cognition at VETSA 2 than VETSA 1 were not supported. Performance in five of nine cognitive domains was correlated with low frequency CS at VETSA 1. Four of these five correlations were significant at VETSA 2. The Study 3 hypotheses of increasing associations between PTA and cognition also were not supported. Low frequency PTA correlated with performance in six cognitive domains at VETSA 1 and in four at VETSA 2. High frequency PTA and episodic memory significantly interacted with age. Neither CS nor PTA was associated with cognition dependent on the sensory modality in which the cognitive tests were presented. The hypothesis that correlations between CS and PTA would increase with age was partially supported, and the hypothesis that correlations between sensory function (vision, audition) and cognition would increase with age was not supported, in both cases because these correlations were independent of age. The results did not follow a single established model of cognitive aging, supporting a model-agnostic approach to future aging research.

This chapter begins by describing the appearance of motor abilities, social and play behavior, sexual maturity, and sensory function in laboratory rats. It then discusses cognitive function, the development of simple stimulus associations made in conditioned taste aversion, and complex associations necessitated in spatial memory. The development of brain structures and their possible role in these behaviors are also discussed.

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<p>Aging erodes motivation, cognition, sensory modalities and physical capacities, effectively depleting quality of life. Declining sensory, cognitive and motor function are reliable biomarkers of aging and mortality risk. These declines are associated with dysregulation of systemic and cellular processes. We developed a complex dietary supplement (DSP) designed to ameliorate five mechanisms of aging (oxidative processes, inflammation, mitochondrial function, insulin resistance and membrane integrity). Remarkably, normal mice fed the DSP retained youthful functionality into old ages, reflecting slower aging rates. Marked improvements in motor function, memory capacity, spatial learning, muscle strength, visual acuity, olfaction, fecundity and important behavioral functions were observed in aging supplemented mice. Conversely, untreated control animals showed age-related declines in all of the above. Functional improvements were associated with reduced oxidative damage, elevated mitochondrial activity, positive cellular energy balance, improved glucose tolerance, boosted neurotransmitters, greater synaptic density and higher neuronal numbers throughout the brain. A 30% reduction in cancer rates was also documented for DSP treated p53+/- mice. The vast functional benefits greatly exceed the modest longevity extension (11%) in normal supplemented mice. For aging humans, maintaining functionality and performance into later years may provide greater socioeconomic and health benefits than simply prolonging lifespan. Implications of these findings extend to common age-related pathologies including dementia and neurodegenerative diseases, diabetes, cancer, sarcopenia and age-related macular degeneration. Although identifying the role of specific ingredients remains outstanding, results provide proof of principle that complex dietary cocktails can powerfully ameliorate biomarkers of aging and modulate mechanisms considered ultimate goals for aging interventions.</p> / Doctor of Philosophy (PhD)