So, about 15 years ago, I read an intriguing paper.   The authors were IM Conboy, MJ Conboy, AJ Wagers, ER Girma, IL Weissman, and TA Rando; Stanford profs all.  What was so intriguing?

They claimed by linking old and new animals (via the circulatory system, called parabiotic binding) for about five weeks, certain age related degenerations could be reversed.  (This paper was published in Nature back in 2005.)

 

 

 

 

 

 

 

Then, basically I heard nothing further.  Until several years ago, when we ran across research still being performed at Stanford.. Dr. Tony Wyss-Coray (Stanford) found that injecting plasma from younger folks seemed to reverse some effects of Alzheimer’s. The research involved injecting the plasma from kids ranging from 18 to 25 into older folks. And, there were improved mental skills, as well as the ability to participate in normal activities for the Alzheimer’s patients who received the transfusions.

The fact is that the majority of our proteins stay the same as we age, but about 1/6 (15%) are altered due to the aging process- or when and if  we are in a diseased state. These proteins, the ones that changed, were called chronokines by Wyss-Coray.

Not surprisingly, Dr. Wyss-Coray formed a firm, Alkahest, to capitalize on this finding. (By the way, the target diseases include Parkinson’s, macular degeneration, as well as Alzheimer’s.) The FDA approved the concept. But, we haven’t heard much about these chronokines, because the bulk of the firm’s studies have been aimed at proving the safety of injecting younger folks blood into Alzheimer’s patients. The research has been able to isolate three chronokines to allow the firm to venture into Stage II clinical trials.

But, now research by Drs. T. Sudhof and K. Gan (Stanford, again) might accelerate such studies. Sudhof and Gan have isolated the individual substances involved in this age-regenerative action. Their study (entitled ‘Specific factors in blood from young but not old mice directly promote synapse formation and NMDA-receptor recruitment’) was recently published in the Proceedings of the National Academy of Sciences.

Their study used two-week old mice and old (12 to 15 months of age) mice, applying the blood serum to human neurons. The young blood induced the growth of some key structures (necessary for neural communication), including the development of more synapses. Those factor include dendritic arborization and an augmentation in the NMDA (N-methyl-D-aspartate) synaptic receptors, among other changes.

However, when the blood from the older mice was applied to the neurons- there were no such changes.

More importantly, the researchers determined that these actions were due to two proteins, THBS4 and SPARCL1.   THBS4 is a thrombospondin protein.  It mediates cell-to-cell and cell-to-matrix interactions and is thought to have an inflammatory role in Alzheimer’s . SPARCL1 is a secreted protein that interacts with the extracellular matrices, mediating cell adhesion.  It also plays a role in inflammation.

More importantly for Alzheimer’s patients,  when those proteins alone were applied to the neurons, the same results- enhanced synapse formation and activity- was manifested.   Without any ‘young’ plasma.

This may be that great leap for which we’ve been hoping!