Oxymetazoline flagged as an anti-aging drug candidate in a Nature Aging framework

Researchers looking for ways to help people stay healthier for longer are increasingly searching for answers in medicines that already exist.

Because drugs that are already on sale have been approved for human use, repurposing them for longevity and ageing research can be faster and less expensive than developing and trialling entirely new compounds.

Even so, pinpointing medicines that might shift biological ageing or influence lifespan remains difficult, simply because there are so many pharmaceuticals to evaluate.

A group at Northeastern University and Harvard Medical School has now proposed a framework designed to narrow the field and highlight the most promising candidates.

Repurposing medicines to target the hallmarks of ageing

In a new study published in Nature Aging, the team describes an approach that links drugs to clusters of genes and proteins associated with the hallmarks of ageing-cumulative, time-driven changes in the body, such as cells having less energy available to function.

Using this method, one candidate that emerged was oxymetazoline. It is sold over the counter as a nasal spray for congestion (branded as Afrin or Sinex), as eye drops for red eyes, and as a topical cream for facial redness caused by rosacea.

Oxymetazoline has not previously been associated with longevity research. However, the team’s analysis suggests it may enhance cell-to-cell communication-another process that typically deteriorates with age, disrupting many biological functions.

"Ultimately, our findings underscore the potential of leveraging the extensive hallmark-associated genetic evidence to identify drug-repurposing candidates for healthy longevity," write the researchers in their published paper.

Mapping ageing genes on the human interactome

The work began with the collection of data on 1,250 genes already linked to at least one hallmark of ageing.

Next, these genes were plotted onto the human interactome-an existing catalogue of the proteins encoded by genes and the ways those proteins interact with one another-in more than half a million distinct interactions.

This mapping indicated that ageing-related genes were not scattered evenly. Instead, they formed clusters in particular regions of the interactome, with different clusters aligning with different hallmarks of ageing. By examining where clusters overlap, the researchers say it becomes possible to spot drugs that may affect multiple hallmarks at once.

"The challenge is figuring out which drugs are worth testing." – network scientist Albert-László Barabási

"If the genes were spread randomly, there is no way for a drug to specifically affect it because it's spread all over," says network scientist Bnaya Gross from Northeastern University.

"[Our] discovery is that aging genes are located in very specific areas, a very specific neighborhood, allowing you to find drugs that affect this neighborhood."

From 6,442 drugs to oxymetazoline and aspirin

With those interactome regions identified, the team then searched for existing medicines likely to influence the relevant genes and proteins, drawing from a list of 6,442 drugs contained in a recognised pharmaceutical database.

At this stage, they added a further measure intended to capture not only which genes a drug targets, but also whether it appears to speed up or slow down ageing-related processes.

This filtering highlighted oxymetazoline, along with other candidates including aspirin, which is already being examined for possible anti-ageing effects.

What the framework can and can’t show

"This study does not provide a cure for aging, nor does it prove that any specific drug will extend human life," says network scientist Albert-László Barabási, from Northeastern University.

"It offers a roadmap… toward actionable interventions that can be tested in cells, animals and eventually humans."

Ageing and age-related disease have many contributing causes, and any efforts to extend lifespan and healthspan may need to address several of them at the same time.

Approaches like this-aimed at identifying which drugs could be most useful, and the reasons why-could help move the field closer to treatments that meaningfully slow biological ageing.

"As someone whose hair turned gray years ago, I share the universal wish that there might one day be a pill that slows aspects of aging," says Barabási.

"The challenge is figuring out which drugs are worth testing."

The research has been published in Nature Aging.

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