James Kirkland and Tamara Tchkonia, researchers at the Mayo Clinic, are at the forefront of a movement focused on stopping chronic disease by targeting aging cells. These so-called “senescent” cells are cells that stop dividing but don’t die. They can build up in tissues due to damage, stress, or — most commonly — aging. And the build-up of these senescent cells is dangerous. They create a toxic, inflamed environment, making a person more susceptible to a number of chronic diseases and conditions linked to aging, including diabetes, stroke, osteoporosis, and more. Could destroying toxic senescent cells mitigate these chronic diseases and reverse aging? Kirkland and Tchkonia’s research explores that very question.
The Senescence Problem
The greatest single risk factor for all human disease is chronological age. One reason for this? Cellular senescence, in which aging or stressed cells enter a state of arrest. Senescent cells stop dividing and multiply, but they do not die. They build up in tissues over time and as a consequence of the aging process. They’ve also been identified as one of the primary mechanisms driving aging and illnesses related to aging, such as cancer, atherosclerosis, diabetes, stroke, and osteoarthritis, because they secrete compounds that create a toxic, inflamed environment primed for these and other related diseases.
Scientists have a number of theories about the evolution and function of senescent cells, which are not in and of themselves toxic. In aging people, however, senescent cells become dangerous because of how long they remain in the tissue. An aging person’s immune system cannot eliminate all of the senescent cells, so they build up in the aging person’s tissues. There they remain, secreting a cocktail of molecules and compounds, triggering an ongoing immune response, damaging surrounding tissues, and stirring up a dangerous environment that could lead to the development of a number of diseases or ailments.
Would a treatment focused on destroying senescent cells be able to reduce the chronic diseases and age-related ailments associated with them? A new movement of researchers believes that it’s possible.
Targeting Old Cells to Reverse Aging
James Kirkland, geriatrician-turned-biochemist, and Tamara Tchkonia, molecular biologist, are two of the researchers at the Mayo Clinic at the head of a new push for therapies that aim to treat chronic disease and slow the aging process by killing senescent cells.
Part of the research has been the search for the senolytics — drugs that kill senescent cells — that effectively target senescent cells while leaving healthy cells intact. Since senescent cells appear to be resistant to apoptosis, or programmed cell death, researchers have focused on finding drugs that would unblock that process. In 2018, Kirkland and Tchkonia’s research uncovered two promising senolytics: dasatinib (a cancer drug) and quercetin (a naturally-occurring antioxidant). Both work by inhibiting cellular enzymes, which ultimately kills senescent cells by allowing them to self-destruct.
Kirkland and Tchkonia conducted initial animal trials using a combination of both dasatinib and quercetin (D+Q). In lab tests, mice who were treated with D+Q demonstrated increased walking speed, endurance, and grip strength. Further trials found that mice who were administered D+Q increased their remaining lifespan by 36 percent compared to mice who were not.
Their discovery in those 2018 animal trials — that senolytic treatment appears to protect against a range of ailments and diseases associated with aging — has been replicated in ongoing studies by other research teams in the years since.
Human Trials in Progress
Thus far, only a few small-scale human trials focusing on the effectiveness of senolytics as a treatment for age-related diseases have been completed. But more are expected in the coming months and years. The National Institute on Aging has committed $3 million in funding over four years to the Translational Geroscience Network (TGN), a multicenter team led by Kirkland, and The TGN is currently running several small preliminary clinical trials looking at the effectiveness of using senolytics for several conditions, including osteoarthritis, Alzheimer’s disease, idiopathic pulmonary fibrosis, chronic kidney disease, and more.
Kirkland and Tchkonia are also looking at how senolytics might eventually help not only with aging, but also with conditions suffered by younger people due to injury or medical treatments like chemotherapy. They’re currently working with SpaceX and Axiom Space to investigate how space radiation affects senescence in astronauts and collaborating with other researchers to look at how senolytics may help expand the pool of available transplant organs.
Although there is a lot of hype surrounding senolytics, scientists urge caution. More data from human trials are needed, and that’s a process that will take time. But there’s reason to be optimistic. Senolytics may eventually be part of a comprehensive treatment strategy that reduces the incidence of a number of painful chronic diseases.
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