The practice of calorie restriction is well established to slow aging, albeit to a lesser degree in long-lived species than in short-lived species. Calorie restriction memetics are compounds that trigger some of the same beneficial mechanisms involved in the response to reduced calorie intake. They do not capture the full effect, but the best of them (such as rapamycin) are nonetheless still beneficial enough to command attention from the research community.
Like rapamycin, the calorie restriction mimetic spermadine has been shown to upregulate the operation of autophagy, an effect presently thought to be the most important aspect of the response to calorie restriction. Long-term treatment with spermadine modestly extends life in mice, to a lesser degree than rapamyin (~10% versus ~25%). Here, researchers focus on clinical trials that measured spermadine levels or treated with spermadine and observed the outcome on cognitive function; the data is mixed, but also not all that consistent, a common issue in the field.
Increasing evidence suggests that caloric restriction (CR) and intermittent fasting may elevate endogenous levels of spermidine (SPD), a polyamine compound now being investigated as a natural caloric restriction mimetic (CRM) candidate. Beyond its endogenous role in cellular metabolism, SPD can be obtained from dietary intake and synthesised by commensal gut microbiota. SPD is involved in several critical biological processes, including cell growth, differentiation, and autophagy, a fundamental mechanism for cellular maintenance and repair. Recognised as a natural inducer of autophagy, SPD is considered an antiageing compound with properties resembling those of CR, positioning it as a potential CRM.
This article provides a comprehensive synthesis of current evidence on the impact of SPD on cognitive ageing, drawing from both observational and interventional studies. A systematic search of major electronic databases identified 22 relevant studies, comprising 4 interventional trials and 18 observational studies. Observational evidence suggests a potential association between SPD levels and cognitive function, with indications of a protective effect against cognitive decline. However, the variability in results, driven by inconsistencies in SPD measurement methods (eg, brain tissue, blood serum/plasma, red blood cells, or dietary intake), poses challenges to drawing definitive conclusions.
Interventional studies offer preliminary evidence suggesting that SPD supplementation may serve as a potential strategy to mitigate age-related cognitive decline. Some studies have indicated positive cognitive effects of SPD supplementation on cognitive function, such as improvements in memory performance and cognitive assessments. However, inconsistencies remain. The observed differences may be potentially due to variations in SPD dosage, the sensitivity of cognitive assessment tools, and other methodological differences.
Link: https://doi.org/10.1136/gpsych-2024-101723
View the full article at FightAging
