Intermittent fasting (IF) is a dietary intervention involving periodic restriction of caloric intake. Common approaches include the 16:8 method and the 5:2 diet. In recent years, IF has emerged as an alternative to continuous caloric restriction in clinical practice, prompting growing interest in its potential effects on aging and longevity. A study published in Nature Cell Biology by researchers at the University of Graz revealed that spermidine, a naturally occurring polyamine, plays a critical role in fasting-induced autophagy and lifespan extension. When endogenous spermidine synthesis was blocked, the autophagy and longevity benefits associated with fasting were significantly diminished. Spermidine is found in various human tissues and dietary sources, including wheat germ, mushrooms, and soybeans. Research suggests that it may support cellular health through several mechanisms, including the regulation of autophagy, oxidative stress, and mitochondrial function. As the global population ages, spermidine has attracted increasing attention as a potential ingredient for healthy-aging supplements. However, its effects on human longevity, the evidence supporting supplementation, and its regulatory status vary across regions and require careful consideration.
Intermittent fasting (IF) is a dietary intervention characterized by periodic restriction of caloric intake. Common approaches include the 16:8 method, which involves fasting for 16 hours and eating within an 8-hour window, and the 5:2 diet, which involves restricting caloric intake on two days of the week. In recent years, IF has become an alternative to continuous caloric restriction in clinical practice. Can IF really delay aging and extend lifespan? A growing body of research has explored this question.
A study conducted by researchers at the University of Graz and published in the Nature journal Nature Cell Biology revealed that the physiological processes through which intermittent fasting induces cellular autophagy and extends lifespan do not depend solely on fasting itself. Instead, they rely heavily on a naturally occurring molecule associated with longevity: spermidine. Once the pathway responsible for synthesizing this molecule is disrupted, the autophagy and lifespan-extension effects associated with fasting are significantly diminished.
1. Introduction to Spermidine
Spermidine is a naturally occurring polyamine compound found widely in human tissues and in everyday foods such as wheat germ, mushrooms, and soybeans. It participates in fundamental biological processes, including DNA replication, mRNA transcription, and protein translation. In 2009, Nature Cell Biology first published research revealing that spermidine could extend lifespan by inducing cellular autophagy.
Figure source: Reference [3]
The human body obtains spermidine through three main pathways: endogenous synthesis, in which arginine serves as a precursor and is converted through putrescine; dietary intake from foods such as wheat germ and legumes; and synthesis by the gut microbiota. Spermidine levels in human tissues, blood, and urine gradually decline with age. In centenarians who maintain good health and longevity, however, spermidine levels may remain close to those observed in middle-aged individuals. For this reason, spermidine has been considered a potential biomarker of biological aging.
In 2017, the European Union included wheat germ extract rich in spermidine in its Novel Food framework. In the United States, spermidine is marketed as a dietary supplement ingredient. By comparison, spermidine has not yet been approved in China as a new food ingredient, a health food ingredient, or a pharmaceutical ingredient. Research and development involving spermidine products in China remain at an early stage, suggesting considerable potential for domestic ingredient applications, formulation development, and the commercialization of health-related products.
2. Mechanisms Through Which Spermidine May Support Longevity
1) An Essential Molecule in Caloric Restriction-Mediated Longevity
Research published in Nature Cell Biology found that spermidine levels increased significantly in yeast, fruit flies, mice, and humans under various fasting or caloric restriction regimens. However, when endogenous spermidine synthesis was blocked through genetic or pharmacological interventions, fasting-induced autophagy was significantly reduced in yeast, nematodes, and human cells, thereby eliminating the lifespan-extension effects of fasting.
The study identified spermidine as a key molecule in caloric restriction-mediated longevity because it activates autophagy pathways and promotes the hypusination of eIF5A, thereby regulating the mechanisms through which fasting contributes to lifespan extension.
Figure source: Reference [1]
2) Induction of Cellular Autophagy
During aging, the regenerative capacity of muscle stem cells declines. Failed autophagy in aged satellite cells and genetically impaired autophagy in younger cells can contribute to cellular senescence, further reducing the function and number of satellite cells.
Research has found that spermidine can inhibit the activation of protein kinase B (AKT), thereby relieving the inhibition of the transcription factor FOXO3. This enhances the transcription of autophagy-related genes and activates autophagic mechanisms that may help improve muscle damage. Through this potential anti-aging mechanism, spermidine has emerged as a candidate for further investigation in age-related muscle atrophy and genetic myopathies.
3) Reduction of Oxidative Stress
Mitochondria are major targets of endogenous free radical attack. Oxidative damage to mitochondria and the resulting genetic mutations are considered important contributors to aging and degenerative diseases. Spermidine may help improve mitochondrial function.
Research has found that spermidine can increase the activity of catalase and superoxide dismutase by activating genes such as ATG3, LC3B, and ULK. It may also reduce reactive oxygen species (ROS) levels and lipid peroxidation, thereby mitigating cellular damage caused by oxidative stress and potentially slowing cellular aging.
3. Market Applications of Spermidine
A recent joint report by a U.S. government agency and Australian academic researchers indicated that, as of 2025, the global population aged 65 and older had reached approximately 852 million, accounting for 10.5% of the world's total population. Meanwhile, children under the age of five accounted for less than 10% of the global population. This marked the first time in recorded history that the number of older adults worldwide exceeded the number of children under five. The continued growth of the global aging population is driving demand for supplements positioned around healthy aging.
According to Precedence Research, the global anti-aging supplements market was valued at USD 4.88 billion in 2025. It is projected to grow from USD 5.28 billion in 2026 to USD 10.49 billion by 2035, representing a compound annual growth rate (CAGR) of 7.95% from 2026 to 2035.
Figure source: Precedence Research
Supplementing with exogenous spermidine has been investigated for its potential to delay aging and reverse unfavorable age-related changes. Spermidine-based anti-aging supplements are already available on the market in various dosage forms, including capsules, tablets, and powders. Target consumers primarily include middle-aged and older adults interested in extending their healthspan, as well as urban consumers seeking anti-aging and oral beauty products.
References
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Hofer, S. J., Daskalaki, I., Bergmann, M., et al. Spermidine is essential for fasting-mediated autophagy and longevity. Nature Cell Biology, 26, 1571–1584 (2024).
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Dai, T., Xu, Y. N., Shen, Y., et al. Spermidine alleviates doxorubicin-induced cardiomyocyte senescence through miR-451-mediated autophagy. Journal of Huazhong University of Science and Technology (Medical Sciences), 53(6): 791–79 (2024).
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Ren, J. L., Yu, T., Gao, X. C., et al. Research progress on the biological activities and development applications of spermidine. Chinese Traditional and Herbal Drugs, 55(16): 5714–5722 (2024).
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Li, H. B., Chen, Z. Y., Lü, X. X. Research progress on spermidine in alleviating cellular senescence and aging-related diseases. Biotechnology Progress, 14(3): 388–398 (2024).
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Ruan, H. L., Xu, Z. M., Chen, Q. Anti-aging mechanisms of spermidine and its application prospects in human skin. China Modern Medicine, 30(35): 21–24 (2023).
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Xie, W. H., Yang, M., Liu, X. G. Research status of metabolites involved in aging intervention. Chemistry of Life, 46(5): 865–876 (2026).