From Longer Life to Cancer
The same molecules that help plants survive drought might also hold the key to human longevity—and pose a hidden risk in our diets.
Imagine if the secret to healthier plants and longer human life lay in tiny molecules found in everything from the soybeans in your tofu to the tomatoes in your salad. These invisible heroes, called polyamines, are among the most ancient and essential compounds in nature, found in every living organism from simple bacteria to humans.
Despite their low profile, polyamines play crucial roles in growth, stress resistance, and aging. Recent groundbreaking research reveals a fascinating paradox: the very same molecules that can promote healthy aging in normal cells may also fuel the growth of cancer cells.
This article explores the dual nature of these remarkable compounds and their potential to revolutionize both agriculture and human health.
Polyamines are low-molecular-weight organic compounds with multiple amino groups that are positively charged at physiological pH. Think of them as tiny, positively-charged magnets that can interact with negatively-charged cellular components like DNA, RNA, and proteins.
The foundational diamine (containing two amino groups)
A triamine (three amino groups) increasingly recognized for its health benefits
A tetraamine (four amino groups) with important regulatory functions
These molecules are not just passive cellular residents; they're dynamic regulators of growth, development, and response to environmental challenges. Their positive charges allow them to bind to and influence the function of various cellular components, making them master regulators of cell activity 2 5 .
In the plant kingdom, polyamines function as natural growth regulators with remarkable influence over virtually every stage of plant development. Research has shown they play critical roles in:
Plants have evolved sophisticated systems for polyamine production and regulation. The biosynthetic pathways begin with the amino acids arginine or ornithine, which are converted to putrescine—the gateway to producing more complex polyamines like spermidine and spermine 2 8 .
The practical applications of polyamines in agriculture are increasingly significant. Farmers and horticulturists can use polyamines to:
Enhance drought and salinity tolerance in crops
Improve seed germination under stressful conditions
Delay senescence and extend the vase life of cut flowers
Improve fruit quality and postharvest characteristics
| Application Method | Crop Example | Observed Benefits |
|---|---|---|
| Seed pre-soaking | Various crops | Improved germination under stress |
| Foliar spraying | Ornamental plants | Extended flower vase life |
| Genetic manipulation | Tomato | Enhanced stress tolerance |
| Pre-harvest treatment | Fruits | Delayed ripening and senescence |
While our bodies can produce polyamines, dietary intake becomes increasingly important as we age and endogenous production declines. Polyamines from food are absorbed through the intestinal tract and contribute significantly to our body's polyamine pool 5 .
The Mediterranean diet, renowned for its health benefits, is naturally rich in polyamine-containing foods. Estimated daily polyamine intake ranges between 250-400 μmol/day, depending on dietary patterns 8 .
Soy products
Aged cheeses
Whole grains
Citrus fruits
Research spearheaded by scientists has revealed that increased polyamine intake, particularly spermidine, can have remarkable effects on health and longevity. Studies have shown that long-term consumption of polyamine-rich food:
The mechanisms behind these benefits are diverse, including activation of autophagy (cellular self-cleaning), antioxidant and anti-inflammatory properties, and potential regulation of age-related changes in DNA methylation 5 .
| Food Item | Polyamine Content | Primary Polyamines Present |
|---|---|---|
| Soybeans | High | Spermidine, Spermine |
| Wheat germ | High | Spermidine |
| Aged cheese | Moderate to High | Putrescine, Cadaverine |
| Citrus fruits | Moderate | Putrescine, Spermidine |
| Chicken | Moderate | Spermidine |
The same polyamines that promise longer, healthier lives have a darker side. Elevated polyamine levels are consistently observed in various cancers and are associated with rapid tumor growth. This creates a troubling paradox: how can the same molecules that promote health in normal tissues fuel disease in cancerous ones? 3
Promote cellular health, longevity, and stress resistance in normal tissues
PARADOX
Fuel tumor growth and proliferation in cancerous tissues
For years, this duality puzzled scientists. The answer, it turns out, lies not in the polyamines themselves, but in how they're utilized by different tissues through distinct molecular pathways.
Groundbreaking research from Tokyo University of Science, published in 2025, has shed light on this paradox. Led by Associate Professor Kyohei Higashi, the team uncovered how polyamines promote cancer growth through pathways distinct from those linked to their beneficial effects in healthy aging 3 .
They first depleted polyamines in human cancer cell lines using specific inhibitors, then manually restored them through spermidine supplementation.
Using cutting-edge liquid chromatography-mass spectrometry (LC-MS) techniques, the team examined changes in over 6,700 proteins in response to polyamine manipulation.
They compared the functions of two highly similar proteins, eIF5A1 and eIF5A2, and their interactions with polyamines.
Further experiments pinpointed the precise molecular mechanism by which polyamines stimulate eIF5A2 production.
The findings revealed a striking divergence in how polyamines act in healthy versus cancerous contexts:
In normal tissues, polyamines activate eIF5A1, which supports mitochondrial function and cellular health through autophagy.
In cancer tissues, polyamines promote the synthesis of eIF5A2, which reprogrammed cellular metabolism toward glycolysis (the Warburg effect) and facilitated cancer cell proliferation.
The researchers discovered that polyamines interfere with a natural suppression mechanism involving a small regulatory RNA molecule called miR-6514-5p, allowing eIF5A2 levels to increase unchecked in cancer cells 3 .
| Characteristic | eIF5A1 (Health) | eIF5A2 (Cancer) |
|---|---|---|
| Primary function | Mitochondrial activation via autophagy | Glycolysis activation |
| Effect on cells | Cellular maintenance & health | Rapid proliferation |
| Regulated by | Normal polyamine activity | miRNA disruption |
| Physiological role | Healthy aging | Cancer progression |
Modern polyamine research relies on sophisticated tools and techniques:
Advanced method for precise polyamine quantification and metabolic profiling without derivatization 7 .
Specially designed polyamine analogs that form covalent bonds with interacting proteins upon UV exposure 9 .
Heavy isotope variants of polyamine precursors that enable precise tracking of metabolic conversions 7 .
Used to create specific polyamine pathway mutants to study gene function 7 .
An irreversible inhibitor of ornithine decarboxylase, used to study polyamine depletion effects 9 .
Polyamines represent both promise and peril—natural compounds essential for life that can be hijacked by disease. The future of polyamine research lies in learning to harness their benefits while minimizing their risks.
Developing treatments that specifically inhibit the eIF5A2 pathway without affecting beneficial eIF5A1 functions
Creating polyamine-rich functional foods optimized for health promotion
Engineering crops with enhanced stress resistance through polyamine pathway manipulation
As research continues, we're learning that context matters enormously with polyamines. The same molecules that nourish us may need careful regulation in certain circumstances. Understanding this balance brings us closer to harnessing the full potential of these ancient molecules for a healthier future 3 5 8 .
For further reading, explore the special issue "Polyamines in Food, Human Nutrition and Health" in the journal Nutrients 1 .