GDF11: A hormonal candidate for rejuvenation
Aging is a program of self-destruction, executed under the control of hormonal signals in the blood. If we can re-balance those signals appropriately, we will be able to revert the body to a younger age. Maybe. In just one day, three papers appeared in major journals reporting on blood factors that can reverse aging.
All three papers come from a line of research called parabiosis. Circulatory systems of a young mouse and an old mouse are surgically joined so that the blood circulating in the veins of the old mouse comes half from the young mouse. The finding from the Conboy Lab in 2005 is that the old mouse is rejuvenated in significant ways. Research since then has sought to separate which factors in the blood are responsible for this effect. Irina Conboy told me last month she has identified 6 key molecules, some of which need to be added, others either removed or de-activated.
Paper #1: (out of Stanford and UCSF and the Palo Alto Center for Regenerative Medicine) “Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level.” Exactly which chemical compounds was not determined, but the benefit was seen both in growth of new neurons in the brain, and also in oberved behavioral changes and improvements in learning among the older animals. The mechanism was traced to biochemical effects in the hippocampus, part of the old mammalian brain that is the first to be damaged in Alzheimer’s disease. In case you’re wondering how you measure cognitive behaior in a surgically-creaed Siamese twin, the answer is that the group was able to see the cognitive benefits when small amounts of the young mouse blood were injected intravenously into the old mouse, eliminating the need for surgerical pairing.
The other two papers were announced in on-line news from Science Magazine, but the original papers are embargoed until Friday. Both involve GDF11, (for “Growth-Differentiating Factor”), which is a hormone common to mice and humans. “GDF11 is naturally found in much higher concentration in young mice than in older mice, and raising its levels in the older mice has improved the function of every organ system thus far studied.” [Doug Melton of Harvard, quoted in Science Daily]
Paper #2: (from Lee Rubin’s group at Harvard) Improvement in l earning behavior and increase in new neurons were both noted with injections of GDF11. “Regardless of the age of the old brain . . . young blood is still able to rejuvenate the aged brain.” “We do think that, at least in principle, there will be a way to reverse some of the cognitive decline that takes place during aging, perhaps even with a single protein. It could be that a molecule like GDF 11, or GDF 11 itself, could” reverse the damage of aging.” [quoted in Science 2.0]
Paper #3: (from Amy Wager’s group at Harvard) also used GDF11, and demonstrates improvements in healing and in muscle growth and strength. “Injections of GDF11 can reduce the thickening of the heart that typically comes with aging in mice…GDF11 works nearly as well as parabiosis in helping aging mice recover from a muscle injury and boosts their performance on running and grip strength tests.”
When dramatic results like this, indicating that some simple intervention is capable of turning back the aging clock, the question everyone avoids asking is, “Why isn’t the body doing this on its own?” The answer, of course, is that the body doesn’t want to. The body is programmed in its genes to age and die, but to acknowledge this is to precipitate a revolution in our understanding of the fundamental mechanisms of evolutionary biology.
This article originally appeared on Josh’s blog here: http://joshmitteldorf.scienceblog.com/2014/05/05/gdf11-a-hormonal-candidate-for-rejuvenation/