How We Can Make Older Bodies Young Again
A researcher from the Stanford Center on Longevity reports on a new discovery that could help maintain muscle tissue well into old age
By Thomas RandoFrom Stanford Center on Longevity November 26, 2012
By Thomas Rando
Credit: Ingram Publishing/Thinkstock
There is something about aging that predisposes us to disease. But there is still much we don't understand about the process. The diseases we associate with getting older are difficult to distinguish from the changes that occur from "normal" wear and tear on the body. If we could somehow figure out the mechanisms and a way to intervene, we could potentially offer therapy for a wide variety of diseases — and not just cancer, heart disease or Alzheimer's. All of them.
In 2011, the Glenn Foundation for Medical Research awarded a $5 million grant to Stanford University to launch a new center for studying the biology of aging, focusing on the role of stem cells. At our new Paul F. Glenn Laboratories, which I direct, we explore how stem cells change as we get older and how that contributes to, or mitigates against, the development of age-related diseases and disorders.
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In our lab, the long-term goal is to find treatments for sarcopenia, the loss of skeletal muscle that occurs with normal aging. Sarcopenia affects muscle mass and strength and is associated with our bodies' inability to maintain healthy tissues as we age. It also perpetuates a vicious cycle: Because our muscles grow weaker as we age, we are more likely to injure ourselves and when we injure ourselves, we are more likely to spend time being sedentary or, worse, go on bed rest, leading to further atrophy. As a result, recovery is slower, which in turn leaves us even more vulnerable to future injuries.
We are working to find ways to maintain human muscle tissue into advanced age. We know that when tissue is injured, stem cells that reside within the muscle jump into action to repair it. In both young and old animals (including, presumably, young and old people), the same basic processes occur, but the stem cell activity in older animals is far less robust. Researchers have always assumed the problem was the integrity of the stem cells themselves — that these cells became damaged with age and so were less able to make repairs.
Our team began to wonder if that was true. We studied muscle stem cells from young and old mice and found that they were really quite similar in terms of their biochemical properties. We hypothesized that the reason stem cells in old animals are less effective in repairing tissue has something to do with their surrounding cells, tissues and blood components.
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To test this hypothesis, we examined how well old muscle recovered from an injury when bathed in the blood of a young animal. Something surprising happened: The stem cell activity in the old tissue was as robust as that in young tissue. Weeks later, when we re-examined the injured tissue, it had healed just as well as young tissue would have. And this was true not only in muscle, but in every tissue we examined, including brain, liver and bone marrow.
Our conclusion was that stem cells do not become irreparably damaged as they age. Rather, their ability to repair tissue is suppressed by the aged environment they reside in. On further study, we identified substances in older animals' blood that suppress stem cell function.
We expect that one day injured older people will be able to take a drug to block one or more of these suppressors, allowing for faster and more effective healing by essentially modifying the biochemistry of the blood and rendering it "young" again.
Perhaps, in this case, we really will be able to teach an old dog new tricks.
Thomas Rando is a professor of Neurology and Neurological Sciences at Stanford University, where he is the director of the Glenn Laboratories for the Biology of Aging and deputy director of the Stanford Center on Longevity. His research on tissue-specific stem cells in aging and disease, and on pathogenetic mechanisms and gene therapy for muscular dystrophies, has broad implications for the fields of regenerative medicine and stem cell transplantation.
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