Anti-aging research has been in the news lately: for instance, here, here and (less recently and less frivolously) here.
Albert Einstein College of Medicine researcher Nir Barzilai, MD, who's spearheading the groundbreaking anti-aging trials referred to in these articles, is far from frivolous. I remember really liking a talk he gave at Stanford a few years ago about his ongoing study of super-old Ashkenazis, at a symposium sponsored by Stanford's Glenn Laboratories for the Biology of Aging.
Now, Tom Rando, MD, PhD, the director of Glenn Labs at Stanford, has co-authored a thought-provoking review in Science that advances a theory of why we age.
It's not the only theory. Judy Campisi of the Buck Institute for Research on Aging, for example, has explored the detrimental activities of differentiated cells gone wrong within our tissues. The older the tissue, the wronger the cells in it go.
Rando and his co-author, Baylor College of Medicine regenerative-medicine expert Margaret Goodell, PhD, come at aging from the opposite end of the spectrum: stem cells, the least-differentiated cells in the body. In particular, Rando and Goodell target the aging-associated actions of so-called somatic stem cells, which reside in virtually all (and, probably, actually all) of our tissues and whose fates are restricted to spawning only cell types that belong in those tissues. While we're growing up, those somatic stem cells are the reason why: They divide to generate the differentiated cells that bulk us up. Once we've matured, they mostly hang back, springing into action to replace tissue lost to injury or to wear and tear.
Radiation, noxious foreign substances, and plain old existence wreaks sporadic damage on somatic stem cells by triggering genetic mutations or by altering the cells' epigenetic settings, the patterns of chemical stop-and-go signs that variously switch the 20,000-odd genes in each cell's genome on or off. These insults pile up as life's pages turn. Eventually, Rando and Goodell write, a curious, Darwin-like natural selection occurs among our tissue-resident stem cells.
What's true for us as organisms is true for our stem cells, too. Every tissue is a jungle, with stem cells continuously competing with one another by proliferating more or less often. Those favored by random genetic or epigenetic changes that confer a growth advantage in the particular environment (i.e., the tissue) that stem cells find themselves in may produce more progeny that then take over the turf.
As the review notes, there's no ageist like evolution, which pretty much stops giving a diddly damn about us once we've reproduced:
[T]he selective environment ... changes with age. In aged organisms, factors such as systemic inflammation may offer an advantage to stem cells with particular characteristics. The stem cells that respond best in an aged or injured environment may not be the most effective at regenerating healthy tissue ... These [dividing] stem cells [are the ones that happen to] have characteristics that confer optimal survival in the protected aging environment, regardless of other functional capabilities.
But this proliferative combat may not really get going in earnest, the authors speculate, until the tissues in which somatic stem cells dwell are plagued by chronic low-level inflammation or some kindred bugaboo of research on aging.
If that's the case, Rando and Goodell reason, it may become possible to stave off the all-against-all struggle of selfish somatic stem cells at the expense of the human bodies they inhabit, say by developing ways to keep our intra-tissue environments chill. (Pass the aspirin, please.)
Previously: Can we reset the aging clock, one cell at a time?, Red light, green light: Simultaneous stop and go signals on stem cells' genes may enable fast activation, provide "aging clock" and Aging research comes of age
Photo by Ben Salter