Ageing, Cognitive Decline, and Effects of Physical Exercise: Complexities, and Considerations from Animal Models

Abstract

In our ageing global population, the cognitive decline associated with dementia and neurodegenerative diseases represents a major healthcare problem. To date, there are no effective treatments for age-related cognitive impairment, thus preventative strategies are urgently required. Physical exercise is gaining traction as a non-pharmacological approach to promote brain health. Adult hippocampal neurogenesis (AHN), a unique form of brain plasticity which is necessary for certain cognitive functions declines with age and is enhanced in response to exercise. Accumulating evidence from research in rodents suggests that physical exercise has beneficial effects on cognition through its proneurogenic capabilities. Given ethical and technical limitations in human studies, preclinical research in rodents is crucial for a better understanding of such exercise-induced brain and behavioural changes. In this review, exercise paradigms used in preclinical research are compared. We provide an overview of the effects of different exercise paradigms on age-related cognitive decline from middle-age until older-age. We discuss the relationship between the age-related decrease in AHN and the potential impact of exercise on mitigating this decline. We highlight the emerging literature on the impact of exercise on gut microbiota during ageing and consider the role of the gut-brain axis as a future possible strategy to optimize exercise-enhanced cognitive function. Finally, we propose a guideline for designing optimal exercise protocols in rodent studies, which would inform clinical research and contribute to developing preventative strategies for age-related cognitive decline.

Keywords: Aging; cognition; exercise; gut microbiota; hippocampus; middle age; neurogenesis; rodents.

Fig. 1

An ageing population is leading to an increase in the prevalence of dementia worldwide. A) Number of people and percentage of global population aged 60 and over in 2000, 2023, and predicated for 2050. Data source: World Health Organization (2023). B) Approximate and predicted numbers of people living with dementia worldwide (2).

Fig. 2

Central and systemic effects of physical exercise. Abbreviations: AHN: adult hippocampal neurogenesis; BDNF: brain derived neurotrophic factor; IGF-1: insulin-like growth factor 1; IL-4: interleukin 4; IL-6: interleukin 6; IL-10: interleukin 10; IL-1β: interleukin 1β; LTP: long-term potentiation; SCFAs: short-chain fatty acids; TNF-α: tumor necrosis factor α; VEGF: vascular endothelial growth factor.

Fig. 3

Stages of adult hippocampal neurogenesis in the dentate gyrus of the hippocampus in adulthood (top panel) and older age (bottom panel). Abbreviations: DCX: doublecortin; DG: dentate gyrus; GFAP: glial fibrillary acidic protein; PSA-NCAM: polysialic-acid neural cell adhesion molecule; SGZ: sub-granular zone; SOX 2: SRY-related HMG box.

Fig. 4

Checklist for planning preclinical experiments involving physical exercise.