Several people emailed me recently for my reaction to media stories on a University of Pittsburgh study in which the short lifespans of mice with a severe form of progeria (accelerated aging) were extended by injections of stem-cell-like muscle cells from young mice. So I took a look at the study and some related research, and here are some things that jumped out at me.
First, it has never been clear how much progerias can tell us about normal aging. Further, it’s not even clear which life-shortening syndromes to anoint as forms progeria, which implies that they have something to do with aging—there are a myriad degenerative diseases that shorten life and cause forms of bodily decay reminiscent of aging’s toll, and it’s a judgment call, sometimes rashly made, to label one of them a form of accelerated aging. Besides, no one knows whether 10% or 90% of the zillion forms of deterioration caused by aging, or something in between, must be present in a purported form of progeria in order for it to tell us truly interesting things about aging. As a general rule, I tend to think that progerias that kill very early in life, as does the one investigated in the Pittsburgh study (it’s called XFE progeroid syndrome, by the way, and it kills mice with a few weeks of birth), are usually less like normal aging than ones that work slower. Thus, I didn’t find the Pittsburgh study all that interesting at first glance—it seemed to be about a possible treatment for a rare congenital disease, not a study on aging.
But I found it more interesting when I took a closer look. The Pittsburgh group has conducted a number of studies over the past few years that suggest XFE progeroid syndrome does indeed resemble something like normal aging at warp speed. Like a number of other purported accelerated-aging syndromes, it hinders the repair of damaged DNA, and there’s much evidence that nicked, bent or otherwise uglified DNA is one of the main drivers of aging. (But determining whether DNA damage is aging’s root cause is almost as hard as deciding whether chickens cause eggs, or vice versa.) XFE progeria broadly induces degenerative changes across organs, including neurodegeneration, early deterioration of vertebral discs, and liver dysfunction. It also engenders patterns of gene activity early in a mouse’s life resembling those that occur late in life in normally aging mice.
The injected cells that extended the lifespans of the progeroid mice in the most recent study—known as MDSPCs, or muscle-derived stem/progenitor cells— were previously shown to be capable of stimulating the regeneration of bone, skeletal and cardiac muscles. The new study is particularly interesting because it suggests that the injected cells secreted factors, currently unknown, that braked degenerative changes in the fast-aging mice. That has raised hopes that these mysterious molecules might be isolated and used to slow such tissue deterioration in normal aging, perhaps by perking up various flagging organs’ tissue-repairing stem cells.
But there are still a lot of reasons to doubt that this research will lead to youth preservatives. For one thing, a few years ago researchers identified the first human case of a genetic defect similar to the one in mice with XFE progeria: it struck an infant that was born with dire defects, including severe head, hand and foot deformities, and led to the baby’s death at 14 months of age—the syndrome looked more like a genetic disease that profoundly messes up development than aging.
Further, great caution is warranted about any intervention that purports to increase cells’ regenerative powers because such treatments can increase the risk of cancer—it’s extremely tricky to juice up normal cell growth without also juicing up the out-of-control growth of tumor cells. This risk is virtually impossible to assess in animals that die at less than a month of age, as did the Pittsburgh mice—cancer generally takes more time to develop than that. Still, I think this story could get a lot more interesting in the near future as researchers further investigate this progeroid syndrome—including a slower-acting, milder form of it that can be induced in mice—and the young-cell-secreted agents that mitigate it.