Since the onset of the COVID-19 pandemic, heightened awareness of our sense of smell has sparked intriguing possibilities.

Researchers at the University of California, Riverside, are exploring the potential of odors, such as those from ripening fruits and fermented foods, to influence gene expression and potentially delaying cancer, inflammation, or neurodegenerative diseases.

(Photo : Unsplash/David Clode)
Odors from Ripening Fruits and Fermented Foods Prompt Gene Expression Changes, Signaling Potential Breakthroughs in Cancer and Neurodegeneration

Fruit Flies Exposed to Yeast-Derived Diacetyl Exhibit Rapid Gene Expression Changes

In experiments led by Anandasankar Ray, a professor of molecular, cell, and systems biology, fruit flies exposed to diacetyl, a microbial volatile compound found in yeast, exhibited changes in gene expression within days.

The research team exposed fruit flies (Drosophila melanogaster) and mice to varying doses of diacetyl vapors over a 5-day period. Diacetyl, a volatile compound released by yeast during fruit fermentation and also produced as a by-product in brewing, was historically utilized to impart a buttery aroma to foods such as popcorn and is occasionally found in e-cigarettes.

Surprisingly, these alterations were observed not only in the fly's antennae but also in mice and human cells. Diacetyl, commonly used in food flavorings, raised concerns due to its unsafe inhalation at high concentrations.

While diacetyl served as a proof of concept, Ray emphasized ongoing efforts to identify other volatiles influencing gene expression, marking the first report of common volatiles behaving this way.

The study, titled "Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs"
published in eLife, reveals that certain odor molecules absorbed into skin, nose, and lungs can fundamentally alter gene expression, prompting questions about their impact on disease predisposition and overall gene expression.

Diacetyl's role as a histone deacetylase (HDAC) inhibitor, along with the discovery of related volatiles with similar potential, suggests potential applications in anti-cancer drugs, inflammatory disease treatment, and neurodegeneration.

Inhibiting HDACs, present in both plants and animals, can lead to less compact DNA winding, enhancing gene expression. This opens avenues for odorant-based HDAC inhibitors to potentially delay neurodegeneration and memory deficits in various diseases.

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Therapeutic Potentials of Scent-Based Health Solutions

Researchers noticed that fruit flies exposed to diacetyl volatiles exhibited a significant slowdown in the degeneration of photoreceptor cells associated with Huntington's disease. Additionally, transgenic mice exposed to diacetyl showed notable changes in gene expression in their lungs and brains, with reduced levels of genes associated with cancers like neuroblastoma.

Human cell lines exposed to diacetyl displayed altered acetylation levels, resulting in increased gene expression, and further tests on human cancer cell lines revealed that diacetyl exposure prevented the proliferation of neuroblastoma.

Beyond its impact on human diseases, the research carries substantial implications for agriculture. Due to the highly conserved nature of HDAC enzymes, which diacetyl inhibits, plants also exhibited strong responses to these volatiles.

Ray noted that exposure to this specific class of odorants could affect any process in plants requiring changes in gene expression, potentially enhancing growth and responses to stress such as freezing and drought.

With the potential to deliver therapeutic doses without the need for pills or injections, volatile chemicals present a novel avenue for both plant and animal health, giving a new dimension to scent-based therapy.

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