Effects of lifespan-extending interventions on cognitive healthspan

Abstract Ageing is known to be the primary risk factor for most neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease. They are currently incurable and worsen over time, which has broad implications in the context of lifespan and healthspan extension. Adding years to life and even to physical health is suboptimal or even insufficient, if cognitive ageing is not adequately improved. In this review, we will examine how interventions that have the potential to extend lifespan in animals affect the brain, and if they would be able to thwart or delay the development of cognitive dysfunction and/or neurodegeneration. These interventions range from lifestyle (caloric restriction, physical exercise and environmental enrichment) through pharmacological (nicotinamide adenine dinucleotide precursors, resveratrol, rapamycin, metformin, spermidine and senolytics) to epigenetic reprogramming. We argue that while many of these interventions have clear potential to improve cognitive health and resilience, large-scale and long-term randomised controlled trials are needed, along with studies utilising washout periods to determine the effects of supplementation cessation, particularly in aged individuals.