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Can medical treatments halt or slow aging?

Post-Bulletin

09-19-17

Sept. 18--A Mayo Clinic researcher is targeting aging itself in an attempt to stave off age-related health conditions.

Doctor James Kirkland, the director of the Robert and Arlene Kogod Center on Aging, is the lead author of a study on senolytic drugs, which could help delay the onset of serious health conditions by clearing the body of senescent, or damaged cells.

Senolytic drug trials may be the next step in keeping people healthier longer.

"If you target fundamental aging processes, you may be able to delay, prevent or target multiple aging issues as a group, instead of one at a time," Kirkland said.

Cellular senescence is only one facet of aging, but Kirkland said there's evidence that targeting one aging process can target all of them.

Aging -- and the fundamental bodily processes thereof -- is the No. 1 risk factor for many health conditions.

"Your risk of getting a heart attack is increased two- to four-fold by your family history, by having high blood pressure or high blood sugar, you know, smoking and other sorts of things," Kirkland said. "Whereas, if you're 85, as opposed to 30, your relative risk is increased a thousandfold."

One thing or another

There's a long list of health conditions that are also associated with aging -- things like Alzheimer's, most cancers, arthritis and osteoporosis.

But physical aging also carries risk of frailty and "loss of resilience," or the ability to recover after an illness like pneumonia or an operation. Age-related conditions tend to appear in force, as well.

"There's this phenomenon of multi-morbidity in older people," Kirkland said. "If you get one age-related disease, the time to get to the next one is not that far away, if you're older. So if you cured, for example, heart attacks, you would be choosing instead to die of something like Alzheimer's or a cancer, or something like that. The next disease would be quick to follow."

Senescent cells can't divide, but don't die, either. Many, but not all, release "noxious" materials which damage and kill other cells and cause "systemic dysfunction."

Senescent cells have "survival pathways" and are immune to their own toxicity, Kirkland said.

Senolytic drugs briefly disable those pathways, so the cells kill themselves.

"In animals, we could clear senescent cells and get a range of outcomes showing improvement in age-related disorders," Kirkland said. "In mice, at least."

So far, research into senescent cells shows that clearing them relieves the mouse equivalents of human age-related diseases like osteoporosis, pulmonary fibrosis, and stiffening of arteries.

Possible treatments

Most recently, Kirkland's team published a paper on the potential to treat multiple age-related illnesses at once with their use.

Senescent cells take weeks or months to develop, but the drugs only need to be in the body for a few hours to disable the cells' pathways and clear them out. So the treatments can be intermittent, instead of continuous (read: chemo, not blood pressure meds).

"That, hopefully, will reduce side effects," Kirkland said. "Because they can be given in periods of relatively good health, they don't have to be given continuously -- at least in mice."

Kirkland envisions that initial clinical trials will be in populations with serious conditions related to cellular senescence -- pulmonary fibrosis, for example, which can be life-threatening -- and will be short-term.

"This is the first use of these kinds of drugs for this purpose in people," he said. "Therefore, we have no idea yet what the side effects and dangers could be, and the kinds of situations where you're trying a completely new therapy like this, are situations where people have a serious condition, and where the risk to them is potentially greatly outweighed by the potential benefit."

Kirkland cautioned the general public not to try to take senolytic drugs until they have been studied and approved.

If the drugs prove safe and effective in a range of serious conditions, then he said the next step would be to see how the drugs work with less-serious conditions like osteoporosis.

There's a long way to go. Small studies with brief endpoints could happen within a year. More complex tests, in a general population with non-serious conditions, will take years.

Fourteen senolytic drugs have been discovered so far. Kirkland and the Mayo Clinic described 11 of those.

"It's an evolution," Kirkland said. "There are many, many instances where drugs look promising in mice and they don't pan out in people. The good thing is that there are multiple different treatments that work in different ways, so there are going to be multiple kicks at the can with this."

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