Endocrine Abstracts

JOINT658

Introduction: Aging is a natural universal and irreversible phenomenon. It is associated with decreased autophagic activity. Spermidine is a naturally occurring polyamine that was discovered in human semen in 1678. Its sources are endogenous (e.g., synthesis by gut microbiome) and exogenous (e.g., dietary intake and supplements). Spermidine is involved in various physiological processes including regulation of autophagy and maintenance of cellular homeostasis. Spermidine administration may be beneficial in the fight against aging. This review presents an update on the role of spermidine in longevity.

Methods: A systematic search of literature was conducted using the search terms spermidine, autophagy, aging, and longevity.

Results: Aging is associated with a progressive deterioration of the cell and organ functioning and the occurrence of several age-related diseases responsible for increased mortality. Autophagy, a major protein turnover pathway that maintains cellular homeostasis under stress conditions, decreases in aging individuals, impacting the longevity. Spermidine plays an important role in cellular growth, regeneration, and regulation. It stimulates autophagy through the inhibition of several acetyltransferases, has anti-inflammatory and antioxidant properties, and positively affects the cell cycle. Stimulation of autophagy is the main mechanism of action of spermidine at the molecular level. Spermidine has the potential to prevent or postpone the occurrence and severity of various age-related diseases (e.g., ischemic heart disease, stroke, chronic obstructive pulmonary disease, cancer, respiratory infection, type 2 diabetes, osteoporosis, and dementia), decrease mortality, and increase longevity. An association between high dietary spermidine intake and reduced mortality has been reported in a cohort of 1,770 healthy subjects aged 39-67 years with a medium follow-up of 13 years. The median of serum spermidine level in normal subjects is around 25 ng/ml and the level declines with aging. Considering the physiological properties of spermidine, foods with high contents of spermidine (e.g., plant-derived products and aged cheese), the Mediterranean diet, and spermidine supplements (spermidine in capsule) may potentially be beneficial for healthy aging and increased longevity. However, the safety of chronic spermidine administration should be further investigated before clinical guidelines are established.

Conclusion: Spermidine regulates a wide range of biochemical and physiological aging processes. Its anti-aging properties is mainly through the stimulation of autophagy. Spermidine can prevent or postpone the occurrence and severity of several age-related diseases. Diet rich in spermidine and spermidine supplements can be beneficial for healthy aging and increased longevity. However, more investigations are necessary to better define the risks and benefits of long-term spermidine administration.