The quest to prolong life has gone on for as long as human existence itself, from the mythical Fountain of Youth to quick-fix fads like intermittent fasting, supplements and injections. But if you take a look in your medicine cabinet, you may unwittingly come across a drug that holds a key to longevity. Could that nasal spray for your stuffy nose be repurposed to reverse one or more of the processes of aging?
A team led by Northeastern University researchers say perhaps. They have found an approach to identify existing drugs that could be repurposed to affect aging, according to research published in Nature Aging on Friday.
Looking at the arsenal of drugs that are already available for new therapies is often cheaper and quicker than developing a whole new drug from scratch, according to experts.
“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,” said Albert-László Barabási, Distinguished University Professor of Physics at Northeastern who oversaw the study, which was undertaken in collaboration with researchers at Harvard . “The challenge is figuring out which drugs are worth testing.”
The researchers specifically looked at aging-related genes that seem to play a role in 11 different biological processes that all influence the concept of getting older. These “hallmarks of aging,” as they are called, include epigenetic alterations, which control when genes are turned on or off and mitochondrial dysfunction, or the decreasing ability for a cell’s powerhouse to produce the energy needed to function.
An important first step that the researchers undertook was to make sense of the different genes involved in aging a postdoctoral researcher in Barabási’s lab at Northeastern and lead author on the study
“You have genes related to aging by some definition or by some reasoning, but it feels like you just have a very big pile of genes related to aging,” he said. “Networks allow us to organize them, saying, ‘OK, it’s not just a pile of genes. They are connected to each other. They form some sort of organization. It’s not a random process.”
The researchers used the Open Genes database, which provides information on genes related to aging and longevity, to narrow down 1,250 genes that are associated with one or more hallmarks of aging. These genes were then mapped out onto a specific part of the human interactome, a comprehensive catalog of over half a million interactions that proteins have with other proteins, as proteins are the targets of most drugs.
The researchers also discovered that aging-related genes were located in very specific areas of the interactome, forming their own modules around the aging hallmarks Knowing that these hallmark modules overlap with where aging genes are found can help researchers identify drugs that affect multiple aging hallmarks, Gross said
“If the genes were spread randomly, there is no way for a drug to specifically affect it because it’s spread all over. [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,” Gross said
With this knowledge Gross said the next question was how these genes, like diseases, could be targeted with therapies?
The way the researchers answered that question was to first investigate the likelihood that any approved drugs could impact these hallmark modules, and then use a metric to determine whether the drug would reverse or accelerate the aging effects
Looking at all the information they were able to glean, the researchers compiled a list of 6,442 drugs from the DrugBank database, which researchers use for information on drugs and drug targets, to understand how close a drug’s therapeutic target was to this aging gene network
Traditionally, drugs targeting diseases are designed to have a specific effect on a specific gene or mechanism, Gross said. But the network can be used to predict the impact of a drug, perhaps on several hallmarks of aging
“The drug does not necessarily need to hit the [aging hallmark module] directly. It can hit in the neighborhood as long as there is a direct path toward it,” he said.
New research found that existing drugs could be repurposed to affect aging. A study led by Northeastern researchers found that aging-related genes sit in a network associated with the “hallmarks of aging.” That network can be used to find existing drugs that reverse or speed up aging. #Aging#AntiAging#Research#Science
At the same time, knowing whether a drug can impact a hallmark of aging only provides part of the picture. It doesn’t say how great the drug’s effect is, nor whether the drug had a positive or negative impact on aging, the researchers said
So Gross, Barabási and their team introduced a metric to gauge that effect, one that compares the activity of a gene through aging against how the drug potentially changes that activity
If a gene becomes less active as one ages, the goal would be to have the drug make it active again, Gross explained. The opposite would need to be true if a gene becomes more active with aging to not amplify the aging-related effect, Gross explained.
The researchers confirmed the confidence in their approach with 17 drugs for longevity currently being tested on people and 11 drugs that have been shown to extend the lifespan of mice. Aspirin, for example, is often prescribed in daily low doses to reduce a person’s risk for heart attack or stroke and is currently being tested in human trials for any longevity benefits.
In this study, researchers found aspirin could be used to positively affect cell-cell communication, which is important for a variety of functions including hormone distribution or immunity, but decreases as we age. The anti-inflammatory drug also worked to deregulate nutrient sensing, the researchers found, which is the ability to detect when your body needs energy
Researchers also used this method to identify 370 drugs that have potential to affect one or more aging hallmarks. Researchers discovered that 14 of those drugs could promote longevity while 14 others were found to have age-accelerating effects
One drug that emerged as a candidate was oxymetazoline, a drug that comes as an over-the-counter nasal spray known as Afrin or Sinex to treat congestion, eye drops for redness or topical cream for redness from rosacea. It does not currently have any known impacts on longevity, but applying their method, researchers found that the drug could be repurposed to improve cell-cell communication. Cell-line experiments are being done with colleagues at Harvard to validate this prediction, looking to identify the exact pathways that the effect has on the cell, Gross said.
While the results are promising, “This study does not provide a cure for aging, nor does it prove that any specific drug will extend human life. It offers a roadmap … toward actionable interventions that can be tested in cells, animals and eventually humans, Barabási said.
The science of aging is complex, Gross said, with one’s genetics, environment and molecular processes all playing a role. The interconnected nature of aging would mean several different interventions to address multiple hallmarks, the study said. If scientists had to take on each aging hallmark by developing a new drug, it would take a decade or more, according to the study.
While the researchers’ methodology identifies drug candidates that have already been tested and have known targets and side effects, further experimentation would be needed to confirm their computations, Gross added. At some point down the line, this method could be used to tailor anti-aging drugs for a specific person, called precise geroscience
“I think we are not there yet,” Gross noted, but “we are moving toward the era of preciseness.”
