Scientists Uncover Link Between Anti-Aging Compounds and Cancer Growth

New research from the Tokyo University of Science has revealed a complex relationship between polyamines, compounds often heralded for their anti-aging properties, and their potential role in promoting cancer growth. On March 2, 2026, findings published in the Journal of Biological Chemistry highlighted how these natural molecules, which are crucial for cellular functions, can simultaneously support healthy aging while being linked to aggressive tumor growth in cancer.

Polyamines, including spermidine, have garnered attention for their ability to stimulate autophagy, a process that helps clear damaged cellular components. This mechanism is largely dependent on a protein known as eukaryotic translation initiation factor 5A (eIF5A1). In healthy cells, eIF5A1 promotes mitochondrial function and cellular maintenance. Yet, researchers have consistently observed elevated levels of polyamines in various cancers, raising questions about how these same compounds can foster both longevity and tumor proliferation.

A Molecular Puzzle in Cancer Metabolism

The intricate connection between polyamines and cancer has been acknowledged for years, but the specific mechanisms at play have remained elusive. Cancer cells often undergo metabolic changes, favoring aerobic glycolysis to rapidly produce energy. Understanding how polyamines influence these shifts is vital for deciphering their dual role in health and disease.

The research team, led by Associate Professor Kyohei Higashi, employed advanced proteomic methods to explore this relationship. They manipulated polyamine levels in human cancer cell lines, first reducing them with a specific drug and then restoring them through the addition of spermidine. This innovative approach enabled the researchers to observe direct effects of polyamines on cancer cell metabolism.

Their analysis, which examined over 6,700 proteins using high-resolution proteomic techniques, revealed that polyamines significantly enhance glycolysis, the rapid conversion of glucose into energy. This finding contrasts with the mitochondrial respiration process, which is more aligned with healthy aging.

Understanding eIF5A1 and eIF5A2 Roles

A crucial aspect of this study was the comparison between eIF5A1 and its closely related counterpart, eIF5A2. Dr. Higashi explained that “the biological activity of polyamines via eIF5A differs between normal and cancer tissues.” In normal cells, eIF5A1, activated by polyamines, facilitates autophagy and mitochondrial function. Conversely, in cancerous tissues, eIF5A2, which is stimulated by polyamines, regulates gene expression to promote cancer cell proliferation.

Further experiments revealed that polyamines increase levels of eIF5A2 by disrupting the regulatory mechanisms that usually limit its production. A small regulatory RNA molecule, miR-6514-5p, plays a key role in this process. By inhibiting this RNA, polyamines allow for higher production of eIF5A2, which in turn affects a distinct set of proteins compared to eIF5A1.

These findings not only clarify the mechanisms by which polyamines influence cell behavior but also highlight their potential implications for cancer therapy. The study suggests that targeting eIF5A2 specifically could slow cancer progression while preserving the positive effects associated with eIF5A1.

This research underscores the importance of biological context in understanding the effects of polyamines. While they may offer anti-aging benefits in healthy tissues, their role in cancerous environments can be detrimental. As scientists continue to explore these compounds, they may develop strategies that harness their benefits while mitigating risks associated with cancer development.

The study received support from various organizations, including the Japan Society for the Promotion of Science and the Hamaguchi Foundation for the Advancement of Biochemistry, highlighting the collaborative effort to unravel these complex biological interactions.