Does aging change docosahexaenoic acid homeostasis? Implications for the challenge to cognitive health in the elderly

¹ Research Center on Aging, Université de Sherbrooke, 1036 Belvedere Sud, Sherbrooke, QC, Canada J1H 4C4
² Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
³ Metabolic Research Centre, School of Health Sciences, University of Wollongong NSW 2522, Australia
⁴ Departments of Medicine and Physiology and Biophysics, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC, Canada J1H 5N4

^* Stephen.Cunnane@USherbrooke.ca

Abstract

Epidemiological studies fairly convincingly suggest that higher intake of fish and omega-3 fatty acids present in fish is associated with reduced risk for age-related cognitive decline (ARCD). Normally, docosahexaenoic acid (DHA) in plasma is positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, ARCD is not consistently associated with lower plasma DHA. Furthermore, DHA is often slightly but significantly higher in plasma and erythrocytes in the elderly without ARCD compared to young adults. Higher plasma DHA in the elderly may be a sign that their fish or DHA intake is higher but we show here that various aspects of DHA homeostasis also change with age. Our supplementation and tracer studies show that DHA metabolism, e.g. transit through the plasma and apparent retroconversion but not beta-oxidation, is different in healthy elderly compared to healthy young adults. Apolipoprotein E4 increases the risk of ARCD, possibly in part because it changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may contribute to making the elderly more susceptible to cognitive decline despite them having similar or sometimes higher plasma DHA than in younger adults.