Water in a sink spirals down the drain. A cell caught in the whirlpool of aging is much the same: it can no longer climb out, and every turn pulls it deeper. Scientists have found what sets this whirlpool spinning: the ApoD protein, which old cells release into their surroundings like a distress signal that actually drowns the neighbors.
It all starts with old cells, like tired swimmers, giving up movement. This was noticed earlier: take the medium in which old fibroblasts (connective tissue cells) were grown, add it to young ones, and the young cells also lose their ability to polarize, the first step toward motion. Now it turns out that ApoD is the culprit. Its level in the medium of old cells is 2.9 times higher than in that of young cells. ApoD does not simply keep a cell from moving; it sets off an entire chain of events inside it.
Once inside a cell, ApoD raises the level of the SUN1 protein. This protein is part of the nuclear bridge that links the nucleus to the cytoskeleton, the way a suspension bridge links two shores. When there is too much of the bridge, it starts yanking at the nucleus, and the cell feels as if it is being shaken nonstop. But the most interesting part is that SUN1 does not merely react passively: it forces the cell to produce even more ApoD. The result is a loop: ApoD raises SUN1, SUN1 raises ApoD. The whirlpool starts to spin.
The loop also triggers other hallmarks of aging: the cell loses lamin B1 (a protein that supports the nucleus from within), its mitochondrial energy potential drops, and levels of reactive oxygen species, molecules that damage DNA, rise. Together, all of this makes the cell truly old. The scientists tested this in mice: inject ApoD into an injured muscle, and it recovers worse, both in mass and in contraction force. The whirlpool of aging pulls under not just individual cells but entire tissues.
So why does aging accelerate after age 60? The ApoD-SUN1 loop provides the answer: when many such loops appear in a tissue, they synchronize, and aging proceeds like an avalanche, the way water first swirls slowly and then roars down the drain. Breaking this loop may mean slowing the whirlpool.
The protein ApoD (apolipoprotein D) was first discovered as a component of high-density lipoproteins, but its exact function long remained a mystery. It turned out to be produced in the brain in Alzheimer's disease and to protect neurons from oxidative stress. Now it turns out that ApoD is also an aging factor that old cells send to young ones to make them "grow old" too.
The idea that aging can be transmitted through blood brings to mind Aldous Huxley's novel Brave New World, where people age and die on a schedule. In reality, the mechanism turned out to be subtler: not just an "aging factor" in the blood, but a feedback loop that amplifies itself.
Not published on arXiv. Here are its page, the PDF and the formalization: you can check it yourself, not only read our account.