Aging's inflammation may start in your blood stem cells (mice)
The inflammation that comes with age may not start where you'd think. In mice, a lot of it may begin in the blood stem cells, deep in the bone marrow. Swap only those stem cells into a young mouse, and its muscle, brain and lung grow old differently.
Change one thing in the marrow. Read it out in muscle, brain and lung.
Here's what they did. They took blood stem cells and switched on an enzyme called SIRT3. They put those cells into young mice and aged them to two years. The stem cells were the only difference. Everything else was the same mouse. And the SIRT3-high mice ran longer on a treadmill, did better on part of a memory test, and had younger-looking lungs.
Inflammation you can't square with wear and tear.
We picture the inflammation of aging as wear and tear. Tissues take damage, so they get inflamed, right where the damage lands. But nobody touched the muscle, brain, or lung. They changed one thing in the marrow, then let the mouse age. If a change sealed in the marrow can decide how a brain ages, the inflammation isn't made where it lands. It's broadcast from upstream.
Aging leaves a memory in the stem cell. SIRT3 erases it.
So how does a stem cell learn to inflame a whole body? Your fast-response immune cells can remember a threat and hit harder next time. It's a real defense. The authors think aging becomes a threat that never lets up. And it trains the blood stem cells themselves. Aging marks their DNA at the inflammation genes. The stem cells pass those marks to the myeloid immune cells they make. So those cells are born primed to inflame. Aging's inflammation isn't only wear and tear. Part of it is a memory, written into the stem cell. SIRT3 erases that memory. And SIRT3 fades with age.
Portable inflammation: a few cells carry it, one antibody undoes it.
So is it really the stem cell, and how does its signal travel? Three tests. First, they moved the immune cells from an old mouse into a young one. The young mouse turned inflamed and weaker. A few altered cells were enough to carry it. Second, they blocked one signal, IL-1β, with an antibody. The inflammation and the weakness went away. So that signal was carrying the harm. Third, they sorted the cells. The myeloid cells carried the effect. The T cells didn't. And SIRT3 only helped from inside the stem cell. Switch it on in grown immune cells alone, and nothing changed.
You can count the training: the inflammatory cells creep up.
Now, the number. As a mouse ages, its stem cells drift toward making the inflammatory cells. In the normal mice, their share of the blood rose from eighteen to twenty-seven percent in a year, and kept climbing. In the SIRT3-high mice, the climb was slower. But here's the catch. The way they kept SIRT3 high was genetic engineering. They switched on an extra copy of the gene, aimed at the stem cells. It was not a pill, not a NAD booster, not a sirtuin supplement. And no one measured how long these mice lived. Every result here is about inflammation, function, and cells.
How does an enzyme in the mitochondria change the marks on the DNA?
One thing still puzzles even the authors. SIRT3 works in the mitochondria, the cell's power plants. Yet the marks changed on the DNA, in the nucleus. How the signal crosses from one to the other, they write, remains to be elucidated. And that missing link is why this isn't a pill. Find what crosses that gap, and you've found what a drug would target.
In these mice, aging's inflammation wasn't only wear and tear — part of it was a memory written into the blood stem cell, and one enzyme kept it from forming.
So in these mice, aging's inflammation wasn't only wear and tear. Part of it was a memory, written into the blood stem cells, carried outward by the cells they make. One enzyme kept that memory from forming. Where it begins may sit further upstream than anyone pictured.
