Strategies for improving cognition with aging: insights from a longitudinal study of antioxidant and behavioral enrichment in canines

Studies in humans suggest that lifestyle factors can have a beneficial impact on the risk for developing cognitive decline and dementia with age. There is growing evidence that maintaining a physically and intellectually active lifestyle can positively impact cognitive ability in older individuals. Dietary factors, such as the intake of antioxidants, may also prevent age-related cognitive decline. However, studies in humans are challenging; many variables cannot be controlled, making it difficult for researchers to determine the exact types and quantities of enrichment and dietary factors necessary for positive effects on cognition. Studies in animal models of human aging allow researchers to precisely control such variables, and can be used to assess the mechanisms and molecular pathways underlying any positive effects. Here we review the results of an intervention study using a canine model of human aging. The study was unique in that it compared the effects of dietary antioxidant supplementation alone and in combination with behavioral enrichment. We found that both interventions lead to improvements in cognitive ability in aged dogs; however, combining the treatments preserved cognition to a greater extent than either treatment alone. Overall, the results suggest that antioxidant supplementation and behavioral enrichment target separate yet complementary molecular pathways to improve cognition, and support the idea that combinations of treatments to improve cognition and slow brain aging will produce greater benefits than single interventions

Molecular Chaperones and Protein Quality Control System in the Canine Model of Brain Aging and Neurodegenerative Diseases

Aged dogs naturally develop cognitive dysfunction and represent a valuable spontaneous animal model for studying normal aging and neurodegeneration. Elderly canines also share neuropathological hallmarks similar to those observed in humans, especially Alzheimer’s disease-like pathology or amyotrophic lateral sclerosis. In addition, pet dogs share similar living conditions and diets to humans. Increasing oxidative damage, as well as alterations of the intracellular protein quality control system, including ubiquitin-proteasome system (UPS) and Heat shock proteins (Hsp), have been observed in the brain of aged dogs. Thus, future researches carried out on the canine spontaneous model may be useful to define the involvement of age-related alterations in Hsp expression and UPS activity in the pathogenesis of neurodegenerative diseases, as well as to perform translational antioxidant treatment/prevention studies. The possibility to design novel therapeutic approaches, including Hspbased therapies, may help to increase chaperone protection against proteotoxic stress occurring in human and canine brain during aging