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Publications total: 16
  Jun 7th,2016

It's all in the blood: Can it really reverse ageing?

Introduction:

Terms or phrases like "fountain of youth" seems appropriate only in the realms of fiction and fairytale but recent scientific evidences are pointing towards a completely different story altogether. Researchers are really excited about a certain protein factor found abundantly in the blood of young individuals that can supposedly reverse or at least slow down the ageing process. Studies have shown that the anti-ageing effect of this protein factor is remarkably visible in the heart tissue, brain and even in the muscles. According to a scientist named Amy Wagers who works with stem cells at Harvard University, this protein factor is produced naturally in the blood and its concentration declines with age (Kaiser, 2014). The factor has noticeable anti-effect in multiple tissues and these observations were further corroborated by another group of researchers who observed that the learning capabilities of old mice improved significantly when injected with plasma taken from young mice (Kaiser, 2014).


Hype or reality:

Age reversal has already generated lot of interest since ages and it is a challenge to determine if things are more hyped up or real. None the less, discovery of the anti-ageing blood reversal factor is a nice starting point and only further studies will tell if the effects are real and substantial. A recent study carried out by Loffredo et al. (2013) reported the isolation of a protein called the growth differentiation factor 11 from the blood of young mice that can potentially arrest age-induced myocardial thickening in old mice. Another recent study was able to demonstrate that the growth differentiation factor 11 can significantly rejuvenate skeletal muscles in old mice. The researchers through the process of parabiosis supplied a recombinant form of the protein to old muscles tissues and observed that the process dramatically improved muscle strength and endurance capabilities (Sinha et al., 2014). Improved healthcare facilities in the 21st century has significantly increased the lifespan of people but the major trade-off of this progress are the age-induced physical and cognitive defects that are putting lot of pressure on the existing healthcare resources. Researchers are under pressure to find ways that can help reduce the effects of ageing and discovery of entities such as growth differentiation factor 11 is generating lot of interest and hope in this regard (Hebert, Scherr, Bienias, Bennett & Evans, 2003); (Bishop, Lu & Yankner, 2010). Another study carried out by Villeda et al. (2014) reported that old mice that received young blood through the process of parabiosis showed significant improvement in the health of dendritic cells and neuronal activity in the hippocampus. Furthermore, the old mice infused with young plasma also showed major improvements in cognitive and learning abilities. These finding have tremendous therapeutic significance for mankind and they lay a solid foundation for the age-reversal therapeutic interventions.

While growth differentiation factor 11 is a relatively new discovery, other agents such as rapamycin and nicotinamide mononucleotide and processes such as cut down in the intake of calories were used for the reversal or arrest of the ageing process in humans (Dvorsky, 2014). So the obvious question that comes to mind here is "What is the advantage of growth differentiation factor 11 over other age reversal agents or techniques?" The simplest answer to the question is its natural abundance in the blood of young individuals and thus easy obtainability. Given the promise of growth differentiation factor 11 in future age reversal therapeutic interventions Harvard University has already filed for a patent on molecule and researchers are already in discussion with organizations that can help them in its commercial release to treat conditions of the heart and Alzheimer's disease (Kaiser, 2014). While there is no doubt in the fact that the protein factor has good therapeutic promise, others believe that the prospect of commercialization is still quite distant. Studies carried out by Loffredo et al. (2013) and (Sinha et al., 2014) at Harvard University that reported the functionality of growth differentiation factor 11 had also used middle aged mice along with old mice and it is not very certain if the same effects could be recreated in humans. Furthermore, there are still no scientific studies that can show that old mice treated with growth differentiation factor 11 actually live longer due to the reversal of age-related effects (Dvorsky, 2014).


Ethical concerns surrounding commoditization of "Blood":

The discovery of the age reversal protein factor and the possibility of its commercialization have raised speculations that blood will become a commodity in the very near future. This in turn raises ethical concerns surrounding the exploitation people especially living in the developing or underdeveloped regions of the world. It is not very hard to foresee a world where the most vulnerable members of the third world societies such as underprivileged children will be forced into blood plasma harvesting camps. While anti-ageing effects are seen in mice there is absolutely no guarantee that similar effects will also manifest in humans. There are no human clinical trials yet and in the event that researchers are successful in finding a way to inject the protein factors into people the risk of cancer will increase substantially. This is because plasma can activate stem cells and studies have shown that this can have a carcinogenic effect in humans. Currently it is not illegal to sell blood plasma like other organs because the body can easily synthesize the plasma that is being taken out of the body. In the event that blood plasma is proved to contain anti-ageing properties without any side-effects a blood plasma black market could appear rather immediately, thanks to the rich and desperate patients who are in urgent need of the same (Interlandi, 2015). However if the current state of research is taken into consideration, the successful reversal of aging process would require blood transfusion in very rapid successions. Unlike other types of organ transplant, people receiving plasma transfusion of age reversal will come under considerable stress on a daily or weekly basis and this raises serious doubts on the viability of blood plasma black market. For these reasons, the researchers who are currently working on the subject are directing their focus primarily on healing and not on age reversal. Researchers are more focussed in finding ways to use the protein factors present in the blood plasma to help aged patients recover faster from surgical procedures. Some human clinical trials have been initiated to see the effect of the plasma in patients suffering from Alzheimer's disease but these studies have very small cohort size and are not undertaken in an extensive manner. As a result the pace of the information coming out of such studies is very slow and will take much long time to arrive upon conclusive evidences.


Conclusion:

The belief that blood drawn from young individuals contains vital ingredients that can give a new lease of life to the elderly is being held by many societies across the globe since ages. Recent scientific evidences in the form of growth differentiation factor 11 has strongly substantiated this long held belief and opened highly interesting avenues for age-reversal interventions. A study carried out by Sinha et al. (2014) reported that the growth differentiation factor 11 (GDF11) plays a major role in the regulation of the ageing process in the muscles and can in fact reverse ageing in the skeletal tissues. This discovery had created a lot of buzz in the scientific community and presented a tremendous promise that in the very new future highly effective age reversal agents will be commercially available in the market. However researchers who are currently involved in the research believe that this is still a distant dream given the lack of substantial human trials. On the contrary a recent study carried out by researchers working at Novartis have lead to findings that raises serious questions on the age-reversal properties of growth differentiation factor 11 (GDF11). The study findings stated that the concentration of growth differentiation factor 11 in blood actually increases with age and not decrease as reported by Sinha et al. (2014) and that instead of rejuvenating the muscle tissues the protein compound actually inhibits muscle regeneration (Egerman et al., 2015). So it appears that a lot for investigation is needed before the age reversal properties of GDF11 could be firmly established and the translocation of the research to human subjects will have to be taken slowly and great caution. The identification of the growth differentiation factor 11 (GDF11) in young blood and its age reversal effect in laboratory mice is major scientific discovery and only time and more scientific investigation will tell if the same effects could be safely realized in humans.


References:

Bishop, N., Lu, T., & Yankner, B. (2010). Neural mechanisms of ageing and cognitive decline. Nature, 464(7288), 529-535. http://dx.doi.org/10.1038/nature08983

Dvorsky, G. (2014). Io9.gizmodo.com. http://io9.gizmodo.com/more-evidence-that-youthful-blood-can-reverse-the-effec-1571870003

Hebert, L., Scherr, P., Bienias, J., Bennett, D., & Evans, D. (2003). Alzheimer Disease in the US Population. Arch Neurol, 60(8), 1119. http://dx.doi.org/10.1001/archneur.60.8.1119

Kaiser, J. (2014). Young Blood Renews Old Mice. Sciencemag.org. http://www.sciencemag.org/news/2014/05/young-blood-renews-old-mice

Loffredo, F., Steinhauser, M., Jay, S., Gannon, J., Pancoast, J., & Yalamanchi, P. et al. (2013). Growth Differentiation Factor 11 Is a Circulating Factor that Reverses Age-Related Cardiac Hypertrophy. Cell, 153(4), 828-839. http://dx.doi.org/10.1016/j.cell.2013.04.015

Sinha, M., Jang, Y., Oh, J., Khong, D., Wu, E., & Manohar, R. et al. (2014). Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle. Science, 344(6184), 649-652. http://dx.doi.org/10.1126/science.1251152

Egerman, M., Cadena, S., Gilbert, J., Meyer, A., Nelson, H., & Swalley, S. et al. (2015). GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration. Cell Metabolism, 22(1), 164-174. http://dx.doi.org/10.1016/j.cmet.2015.05.010

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