Monday, July 21, 2014

Reversing Aging

In a study in 2013, a team at the Harvard Stem Cell Institute reported (1) that combining  the circulatory systems of an older mouse and a younger mouse in a surgical procedure called parabiosis improved the structure and function of the enlarged hearts of older mice, otherwise known as cardiac hypertrophy, which is a common cause of heart failure in humans. The hearts became smaller and there was molecular remodeling. They then found that the blood of older mice had less of a protein growth factor called GDF11 than blood of younger mice, and that administering GDF11 to older mice had similar effects as administering blood. GDF11 is also found in human blood.

In a separate paper (2) the same team showed that GDF11 reversed the structure and function of aged muscle to that of younger muscle and increased strength and exercise capacity. In a third paper (3) they showed that young blood, as well as GDF11 alone, improved the vascular structure of the brain and caused the creation of new nerve cells.

In yet another study at Stanford University (4) researchers found that administering young blood to aged mice can reverse pre-existing effects of brain aging at the “molecular, structural, functional and cognitive level.” Synaptic plasticity and dendritic spine density increased in the hippocampus of aged mice. Cognitive abilities improved in fear conditioning and spatial learning and memory. The study used the blood of young mice and did not try to identify any specific factors.

Taken together, these studies show that there are proteins (GDF11 is probably only one such factor out of many that will soon be isolated) in young mice (and probably humans) which decrease over the lifespan of the individual to cause aging. Re-administering these factors to aged individuals does not only stop the aging process but can reverse it. To say that this is a game-changer is an understatement.

Of course, there can be many side-effects that may arise with tinkering with some of the genetic factors in the aging process, increased risk of cancer being one of them. But aging is based in our DNA, and DNA is a code. Any code can, and will, be broken. I have no doubt that in the not too distant future a safe combination of drugs will be developed for reversing some, or all, of the aging mechanisms of our bodies.

Already venture capitalists are circling. Peter Barrett of Atlas Venture and a co-founder of Celera Genomics—the first private company to map the human genome—is planning on creating a new company that will use these results to develop human drugs for reversing the aging process. Tony Wyss-Coray, of the Stanford group, has cofounded a biotech company called Alkahest to develop similar products. It may not be too long before a cocktail will be developed which can be injected into aged individuals to revert them to an earlier, younger, self.

In the meantime, some elderly members of society—those who can afford it—may decide not to wait. I can imagine an entire industry forming which will offer the blood of the young for transfusion into the elderly to reverse aging. But before we proceed much further, we need to have a mature discussion about what creating a society of ageless, or long-lived, individuals will look like. Spoiler alert: it will look nothing like it does today. Severely restricting reproduction—a great challenge in our own society, never mind globally—is the most obvious consequence, but certainly not the only one. But that is for another posting.

Welcome to the future.

1.     Loffredo et al., Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy, Cell, Volume 163, Issue 4, 9 May 2013, Pages 828–839
2.     Sinha, et al., Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle, Science 9 May 2014: Vol. 344 no. 6184 pp. 649-652 DOI: 10.1126/science.1251152
3.     Katsimpardy et al., Vascular and Neurogenic Rejuvenation of the Aging Mouse Brain by Young Systemic Factors, Science 9 May 2014: Vol. 344 no. 6184 pp. 630-634 DOI: 10.1126/science.1251141
4.     Villeda et al., Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice, Nature Medicine 20, 659–663 (2014) doi:10.1038/nm.3569