Spermidine Promotes Cardioprotective Autophagy
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Cardioprotection and lifespan extension by the natural polyamine spermidine
Eisenberg et al
Nat Med. 2016;22:1428–1438
A recent study published in Nature Medicine reports that dietary supplementation with spermidine, a natural polyamine, extends life span and reverses aging-associated cardiac dysfunction in mice through induction of autophagy. Similar protective effects of spermidine on human cardiovascular health were also suggested by epidemiological studies.1
Our population is aging—shifting in distribution toward older age—at an unprecedented pace. Based on US population reports, the percentage of people aged >65 years is estimated to increase from 13.4% in 2012 to 19.3% in 2030. And as aging is the greatest risk factor for major life-threatening disorders, including cardiovascular and neurodegenerative diseases, metabolic syndromes, and cancer, these demographic shifts are of great significance.2 Furthermore, the simple extension of longevity falls short of the over-riding objective of extending healthy life (square-waving life). Therefore, there is great interest in interventions that target the aging process per se, as they could potentially provide novel preventive and therapeutic approaches for a wide range of age-associated diseases.
In the past 2 decades, studies have identified multiple genetic and pharmacological interventions that extend the lifespan of model organisms, including yeast, worms, flies, and mammals. Caloric restriction (CR), and pharmacological agents that mimic the effects of CR, including rapamycin, metformin, resveratrol, and spermidine, promote longevity in model organisms.3 Interestingly, most interventions converge on a limited number of common cellular processes, including nutrient signaling (insulin and mechanistic target of rapamycin [mTOR] pathways), mitochondrial efficiency, and autophagy. Both CR and inhibition of nutrient signaling induce autophagy, an evolutionarily conserved mechanism that targets damaged or long-lived proteins and organelles for degradation. Autophagy is downregulated over the course of aging, and inhibition of autophagy abolishes the longevity-promoting effects of many manipulations, indicating a strong connection between …