Mayo’s Kogod Center On Aging Spawning Spinoffs, Breakthrough Research

After launch of Unity Biotechnology, study links osteoarthritis to ‘senescent’ cells.
Mayo’s Kogod Center On Aging Spawning Spinoffs, Breakthrough Research

The same Mayo Clinic lab that earlier this year spawned a buzzworthy anti-aging startup firm has recorded another research breakthrough connecting “senescent” human cells to age-related maladies—in this case, osteoarthritis.
The Robert and Arlene Kogod Center on Aging at Mayo Clinic is the home of researchers Jan van Deursen and Dr. James Kirkland (its director). They and colleagues have been investigating the role played in the aging process by senescent cells—living cells that have stopped reproducing due to age or damage.
Such senescent cells should destroy themselves or be eliminated by the body’s immune system, but some survive and emit secretions that harm surrounding tissue and influence other nearby cells to also become senescent. Cellular senescence is regarded as one of the root causes of degenerative aging, but its role in age-related diseases such as osteoarthritis, glaucoma and atherosclerosis has been speculative and largely unproven.
That changed in February when Van Deursen co-published groundbreaking research demonstrating how cellular senescence is linked to the aging process in mice. Specifically, his study showed that removing senescent cells extends the lives of otherwise normal mice by 25 percent. And crucially, it also showed that removing such cells actually sets back aging process, delaying the formation of eye cataracts, the onset of heart and kidney deterioration and even tumor formation.
Those results opened the possibility of developing a whole new class of drug therapies targeting cellular senescence as an anti-aging strategy and led to the creation this year of San Francisco-based Unity Biotechnology, co-founded by Van Deursen and backed by Mayo Clinic Ventures. Its initial funders also included the well-known VC firms ARCH Venture Partners and Venrock.
The cellular senescence research program at Mayo is so promising that it’s one of the clinic’s most generously funded by the U.S. National Institutes of Health. The effort has received more than $1.9 million in NIH funding this year, and this month Dr. Kirkland and a group of colleagues published a study that for the first time demonstrated a causal relationship between senescent cells and an age-related illness – specifically, osteoarthritis.
Osteoarthritis (OA) is the most common form of arthritis in the elderly, causing widespread pain, disability, and immobility. Currently it is treatable only though pain management, joint replacement and mobility aids such as wheelchairs and walkers. Overall in the United States, OA in 2005 affected 33.6 percent of those 65 older (some 12.4 million people). Its estimated costs due to hospital expenditures for total knee and hip joint replacements were $42 billion in 2009, according to the U.S. Centers for Disease Control and Prevention.
Thus, a potential drug therapy that could effectively target osteoarthritis could be a true paradigm-shifter both in improving elderly patients’ quality of life and reducing a massive healthcare cost center.
Mounting evidence had associated osteoarthritis with the accumulation of senescent cells in or near joints. However, evidence for a causal link between OA and cellular senescence had been lacking until now. In Dr. Kirkland’s study, researchers transplanted senescent cells from the ear cartilages of lab mice into the knee joint area of wild mice, and by using scanning imaging, kept track of the injected cells for more than 10 days.
What they found was that transplanting senescent cells into the wild mice caused leg pain, impaired mobility and other changes suggestive of OA. Transplanting non-senescent cells, meanwhile, produced fewer effects. Thus it was shown that senescent cells could induce an OA-like state, leading to the conclusion that “targeting senescent cells could be a promising way to prevent or alleviate age-related osteoarthritis.”
“Osteoarthritis has previously been associated with the accumulation of senescent cells in or near the joints, however, this is the first time there has been evidence of a causal link,” Kirkland said in a Mayo press release. “Additionally, we have developed a new senescent cell transplantation model that allows us to test whether clearing senescent cells alleviates or delays osteoarthritis.
“While there is more work to be done, these findings are a critical step toward that goal.”