Spermidine

Spermidine is a natural polyamine ubiquitously found in organisms from all kingdoms and present in common food items. ^[1] It is described as a caloric restriction mimetic, an agent that mimics the beneficial effects of dietary restriction while limiting its detrimental effects. ^[2] The major polyamines are putrescine, spermidine, spermine, and cadaverine, and their cellular levels are tightly controlled. ^[3]

Mechanistically, spermidine induces protein deacetylation and depends on functional autophagy, sharing the molecular pathways engaged by other caloric restriction mimetics. ^[2] It preserves mitochondrial function, exhibits anti-inflammatory properties, and prevents stem cell senescence. ^[2] Caloric restriction mimetics such as spermidine act by promoting autophagy, a cytoplasmic recycling mechanism, via a reduction in protein acetylation. ^[4]

In model organisms, spermidine prolongs the lifespan of fungi, nematodes, insects and rodents, and in mice it also postpones the manifestation of age-associated disorders such as cardiovascular disease and neurodegeneration. ^[1] In rodent models the natural polyamine spermidine has prominent cardioprotective and neuroprotective effects and stimulates anticancer immunosurveillance. ^[2] In human epidemiological studies, dietary polyamine uptake correlates with reduced cardiovascular and cancer-related mortality. ^[2] In an assessment grouping interventions to slow ageing by the robustness of preclinical and some clinical results, spermidine is placed in the top tier of candidates alongside rapamycin, senolytics and metformin. ^[5] Spermidine is among a set of promising drugs and natural compounds that have been tested in the clinic as candidate

Spermidine levels experience an age-related decrease, and the development of age-related diseases is correlated with decreased endogenous spermidine concentrations. ^[7] Because spermidine is already present in daily human nutrition, clinical trials aiming to increase the uptake of this polyamine appear feasible. ^[2] Its specific features, including its presence in common food items, make spermidine an interesting candidate for translational aging research. ^[1]