Wednesday, 1 July 2015

Money in circulation

Supplementary material

The quest for eternal youth, or at least for a slowed-down decay, has always been a strong motivation for explorers and researchers, be they Ponce de León, calorie-restriction aficionados or a fictional Dr. Obispo. Be the solution anti-wrinkle creams, dietary supplements, spinach and turmeric smoothies or jogging, we're pretty much ready to try it all to prolong our stay on this mortal coil.

In the lab, we try to decipher the riddle of aging; how is it that some species age more slowly than others? How is it that some individuals age faster? How can we control cellular senescence to better our lot as individuals? This is all fascinating in and of itself, and may have practical applications too. (Hey, I ain't proud... I'd like to live longer as much as anybody else!)

Recent work using the technique of parabiosis has led to quite startling observations in the field of aging. Parabiosis is a technique by which the circulatory system of two animals are linked, so that the blood of one mixes with that of the other. (Naturally, the animals in question had better not be immunologically incompatible)!

More specifically, the experiments I refer to played with the age of the parabiotes, linking an old mouse with a young one (as well as two young ones and two old ones together as controls). This connection of old and young mice is called heterochronic parabiosis. The idea was, succinctly put, to see whether there was something in the blood of old mice that caused their tissues to age (think "accumulation of garbage") and whether there was something in the blood of young mice that kept them young (think "youth serum"). In the first case, it was expected that the unknown noxious factors present in the blood of the old mouse would cause its younger counterpart to show increased signs of aging. In the other case, it was possible that aged tissues would show signs of rejuvenation because of whatever came from the blood of young mice.

The results were noteworthy, to put it mildly: there was indeed something in the young blood that could cause the rejuvenation of several systems and tissues in the old mouse, without the young one apparently suffering for it. (This latter point seems to be slightly less true with increasing age for the "old" parabiote). The circulatory system of the old guy seemed to regenerate itself more efficiently, its cognition was increased, it showed lower stem cell depletion, its age-related cardiac hypertrophy was diminished... nothing but good news!

Further analysis of the phenomenon identified a particular protein that seems to play an important role in this Foutain of Youth effect: the signalling protein GDF11. This circulatory factor sees its level drop with increasing age, a drop that parallels progressive cardiac hypertrophy. Restoring GDF11 levels reverses the hypertrophy. GDF11 will also induce vascular remodelling that leads to increased neurogenesis.

Two papers on GDF11 and its amazing effects were seen as the 2014 breakthrough of the year in the biomedical field by the journal Science:

Sinha et al. (2014) Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle. Science 344, 649-652

Katsimpardi et al. (2014) Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors. Science 344, 630-634

Spookingly, the discovery that it is possible to make old individuals younger by using the blood of younger ones is the same concept that was the basis for the science-fiction novel Bug Jack Barron, written by the amazingly creative Norman Spinrad in 1969. In that story, old rich people could be made to live forever thanks to an extract made from unspecified glands in the body of young children (who, for dramatic purposes, were killed in the process).

Hopefully it won't come to that! Using the blood of the young to keep the old alive is basically what vampirism is all about! I'll settle for some recombinant GDF11, thank you.