Now, all you dirty old men as well as members of the PC Police – relax! I know what your fevered imagination is conjuring up. That’s not what I’m talking about. But before I plunge into a truly fascinating research, let me begin with a personal story.
In my early days as a researcher, I was struck by the phenomenon of thymus involution, meaning that as we age the thymus gland loses its volume, cell number, and function. Turning this statement on its head, could it be that as a consequence of thymus loss of function we undergo the aging process? The implication of that could be profound: aging may not be an unavoidable process if we could only keep the thymus gland fully functional.
The function of the thymus
The thymus has an important function: it is responsible for the “education” of T lymphocytes, a critical component of the immune response, to recognize “self” from “non-self,” thus endowing us with defense against foreign invaders, like parasites, bacteria, and viruses, while avoiding destruction of “self” tissues (autoimmunity). To test this hypothesis I selected a short-lived strain of mice (AKR strain) and periodically grafted thymus from young mice into the aging mice. There was only a slight problem: most of the older mice succumbed to the anesthesia; only about 5% survived, but they actually had a longer life span, and their T cell function was youthfully intact. It was impractical to pursue this research with such a high mortality, so I just moved on, abandoning this line of investigation.
You can imagine my satisfaction when I read a Nature article by Amy Wagers and Irving Weissman of Stanford in which they hooked up young mice to old mice and rejuvenating the old mouse livers. A factor in the young blood prompted liver stem cell proliferation in the oldsters. Hooking up two blood circulations is called parabiosis, and when animals of two different ages are involved it is called heterochronic. This heterochronic parabiosis experiment wasn’t a one-off.
Amy Wagers, now at Harvard, followed up with a paper titled Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy showing that the pathological changes of the aging heart, such as thickening of the cardiac walls, are reversed by heterochronic parabiosis, and that the factor responsible for this effect is called DGF-11.
If that’s not exciting enough, read on.
“Remyelination is a regenerative process in the central nervous system (CNS) that produces new myelin sheaths from adult stem cells. The decline in remyelination that occurs with advancing age poses a significant barrier to therapy in the CNS, particularly for long-term demyelinating diseases such as multiple sclerosis (MS). Here we show that remyelination of experimentally induced demyelination is enhanced in old mice exposed to a youthful systemic milieu through heterochronic parabiosis. Restored remyelination in old animals involves recruitment to the repairing lesions of blood-derived monocytes from the young parabiotic partner, and preventing this recruitment partially inhibits rejuvenation of remyelination. These data suggest that enhanced remyelinating activity requires both youthful monocytes and other factors, and that remyelination-enhancing therapies targeting endogenous cells can be effective throughout life.”