New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases

High incidences of morbidity and mortality associated with age-related diseases among the elderly population are a socio-economic challenge. Aging is an irreversible and inevitable process that is a risk factor for pathological progression of diverse age-related diseases. Spermidine, a natural polyamine, plays a critical role in molecular and cellular interactions involved in various physiological and functional processes. Spermidine has been shown to modulate aging, suppress the occurrence and severity of age-related diseases, and prolong lifespan. However, the precise mechanisms through which spermidine exerts its anti-aging effects have not been established. In this review, we elucidate on the mechanisms and roles underlying the beneficial effects of spermidine in aging from a molecular and cellular perspective. Moreover, we provide new insights into the promising potential diagnostic and therapeutic applications of spermidine in aging and age-related diseases.

The Regulatory Effect of Biogenic Polyamines Spermine and Spermidine in Men and Women

"The incidence and prevalence of infertility and sexual dysfunction in men and women is increasing. The biogenic polyamines spermine and spermidine are important for sexual function as well as fertility." "The biogenic polyamines spermine and spermidine appear to support a trend toward hormone balance,

Mechanisms of spermidine-induced autophagy and geroprotection

Great review article from Nature Aging detailing updated understanding of the science of spermidine.

Spermidine ameliorates high-fat diet-induced hepatic steatosis and adipose tissue inflammation in preexisting obese mice

Spermidine administration improved high-fat diet-induced glucose tolerance.
Spermidine attenuated hepatic steatosis and reduced fat inflammation.
Spermidine promoted brown adipose tissue thermogenesis.
Spermidine enhanced gut barrier function in obese mice.

Spermidine in Health and Disease

Review article published in Science that serves as a great starting point in your spermidine research.

A spermidine-based nutritional supplement prolongs the anagen phase of hair follicles in humans: a randomized, placebo-controlled, double-blind study

Spermidine has been shown both in vitro and in mice models to have an anagen-prolonging effect on hair follicles (HFs). To evaluate the effects of a spermidine-based nutritional supplement on the anagen phase of HFs in healthy human subjects in a randomized, double-blind, placebo-controlled trial. One hundred healthy males and females were randomized to receive a tablet containing a spermidine-based nutritional supplement or a placebo once daily for 90 days.

Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions.

Rapidly regenerating tissues need sufficient polyamine synthesis. Since the hair follicle (HF) is a highly proliferative mini-organ, polyamines may also be important for normal hair growth. However, the role of polyamines in human HF biology and their effect on HF epithelial stem cells in situ remains largely unknown.

Induction of autophagy by spermidine promotes longevity.

Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells.

Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?

Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy. External supplementation of spermidine extends lifespan and health span across species, including in yeast, nematodes, flies and mice. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested.

Higher spermidine intake is linked to lower mortality: a prospective population-based study.

Spermidine administration is linked to increased survival in several animal models. The aim of this study was to test the potential association between spermidine content in diet and mortality in humans. This prospective community-based cohort study included 829 participants aged 45–84 y, 49.9% of whom were male. Diet was assessed by repeated dietitian-administered validated food-frequency questionnaires (2540 assessments) in 1995, 2000, 2005, and 2010. During follow-up between 1995 and 2015, 341 deaths occurred.

The importance of dietary polyamines in cell regeneration and growth.

The polyamines putrescine, spermidine and spermine are essential for cell renewal and, therefore, are needed to keep the body healthy. It was previously believed that polyamines are synthesized by every cell in the body when required. However, in the present paper evidence is provided to show that, as in the case of the essential amino acids, the diet can supply sufficient amounts of polyamines to support cell renewal and growth.

Spermidine Prolongs Lifespan and Prevents Liver Fibrosis and Hepatocellular Carcinoma by Activating MAP1S-Mediated Autophagy.

Liver fibrosis and hepatocellular carcinoma (HCC) have worldwide impact but continue to lack safe, low cost, and effective treatments. In this study, we show how the simple polyamine spermidine can relieve cancer cell defects in autophagy, which trigger oxidative stress-induced cell death and promote liver fibrosis and HCC.