In recent years, fasting has become the new favorite of the scientific community, fasting has been shown to lose weight and extend the life span of animals, in fact, a growing number of studies show that fasting has many health benefits, improving metabolic health, preventing or delaying diseases that come with aging, and even slowing the growth of tumors.
Intermittent fasting, like caloric restriction, has been shown to extend the lifespan and healthy lifespan of model animals such as yeast, nematodes, fruit flies, and mice. In humans, intermittent and long-term fasting, as well as continuous caloric restriction, have favorable effects on multiple health-related parameters that may have a common mechanistic basis, and there is strong evidence that autophagy mediates these effects.

In addition, spermidine (SPD) has been similarly associated with enhanced autophagy, anti-aging, and reduced incidence of cardiovascular and neurodegenerative diseases across species.

On August 8, 2024, Researchers from the University of Graz in Austria, the Sorbonne in Paris and the University of Crete in Greece published a paper entitled "Spermidine is essential for fasting mediated autophagy" in the journal Nature Cell Biology and longevity "research paper.

Studies have shown that spermidine is necessary for faster-mediated autophagy and longevity, and that the improvement of life span and health span by fasting in multiple species is partially dependent on spermidine-dependent eIF5A-hypusination modification and subsequent induction of autophagy.

In mammals, age-related reductions in autophagy flux promote the accumulation of protein aggregates and dysfunctional organelles, as well as failure of pathogen clearance and increased inflammation.

Inhibition of autophagy at the genetic level accelerated the aging process in mice. The loss of functional mutations in genes that regulate or perform autophagy has been causally linked to cardiovascular disease, infectious disease, neurodegenerative disease, and metabolic, musculoskeletal, eye, and lung diseases, many of which resemble premature aging. In contrast, autophagy stimulation at the genetic level promotes longevity and healthy longevity in model animals, including fruit flies and mice.

In addition to nutritional interventions, the use of natural polyamine spermidine on model animals such as yeast, nematodes, fruit flies, and mice is another strategy to extend lifespan in an autophagy dependent manner. In addition, spermidine can restore autophagy flux in circulating lymphocytes in the elderly, which is consistent with the observation that increased dietary spermidine uptake is associated with reduced overall mortality in humans.

Spermidine is a kind of natural polyamine that exists widely in organisms. In recent years, more and more studies have shown that spermidine has magical and powerful anti-aging effects.

Thus, fasting, caloric restriction, and spermidine prolong the lifespan of model animals and activate a phylogenetically conserved, autophagy dependent protective effect in old age. In this latest study, the research team further explored whether the geriatric protective effects of intermittent fasting are related to or dependent on spermidine.

The study found that spermidine levels increased in yeast, fruit flies, mice and humans under different fasting or caloric restriction regimens. Genes or drugs that block endogenous spermidine synthesis reduce faster-induced autophagy in yeast, nematodes, and human cells.

In addition, interfering with the polyamine pathway in the body can eliminate the prolonging effects of fasting on longevity and healthy life, as well as the protective effects of fasting on the heart and anti-arthritis effects.

Mechanically, spermidine mediates these effects by inducing autophagy and hypusination of eukaryotic translation initiation factor eIF5A. The polyamine-Hypusination axis is a phylogenetically conserved metabolic regulatory hub in faster-mediated autophagy enhancement and life extension.

Overall, the study suggests that the improvement of fasting on longevity and healthy life span in multiple species is partially dependent on spermidine-dependent eIF5A-hypusination modification and subsequent induction of autophagy.