Chrono-Gerontology: Integrating Circadian Rhythms and Aging in Stroke Research

Stroke is a significant public health concern for elderly individuals. However, the majority of pre-clinical studies utilize young and healthy rodents, which may result in failure of candidate therapies in clinical trials. In this brief review/perspective, the complex link between circadian rhythms, aging, innate immunity, and the gut microbiome to ischemic injury onset, progression, and recovery is discussed. Short-chain fatty acids and nicotinamide adenine dinucleotide⁺ (NAD⁺) production by the gut microbiome are highlighted as key mechanisms with profound rhythmic behavior, and it is suggested to boost them as prophylactic/therapeutic approaches. Integrating aging, its associated comorbidities, and circadian regulation of physiological processes into stroke research may increase the translational value of pre-clinical studies and help to schedule the optimal time window for existing practices to improve stroke outcome and recovery.