It remains an open question as to the degree to which the mechanisms that cause progeria are relevant in normal aging. They are present at very low levels in old people, a very different picture from the upheaval and dysfunction taking place in the cells of progeria patients. Are those low levels meaningful over the course of a normal human life span, and in comparison to the known causes of degenerative aging? Time will tell, but it can't hurt to keep an eye on progress in progeria research, which seems to be on the verge of a more effective class of therapies:
Though researchers identified the abnormal protein behind progeria - progerin - the exact way in which it causes the accelerated aging remains elusive. Progerin, a protein present in very high concentration in progeria cells, is known to be responsible for many of the characteristics of the disease. It is a mutant version of lamin A, a protein crucial for the stability of the nucleus and involved in many essential nuclear functions. "A few years ago, we and others found that progeria cells have much less LAP2α than normal cells. LAP2α is a protein that interacts with lamin A to regulate cell proliferation, the process that produces new cells. Interestingly, LAP2α levels also decrease during normal aging. The cells that produce progerin had really low LAP2α levels compared to normal cells. But when we re-introduced LAP2α we could completely rescue the proliferation defect of the progeria cell line. The same actually happened in cells from patient samples."
Further experiments revealed a real surprise: LAP2α functions very differently in progeria cells compared to normal cells. Usually it binds to a distinct nuclear pool of lamin A and slows proliferation, so low LAP2α levels result in hyperproliferation. But in progeria the opposite is the case, cells proliferate much slower and prematurely enter the cellular aging process. The reason for this is that progeria cells do not have the nuclear lamin A pool. This hinted that LAP2α uses a different route to exercise its function in progeria cells. In the end, data from previous experiments gave the researchers the clue to solve the puzzle. "Cells are surrounded by material that structurally supports them. It is called extracellular matrix or in short ECM. It was reported before that progerin negatively affects the production of ECM proteins, leading to a disrupted cellular environment and slower proliferation. Now we connected this to the low LAP2α levels and when we reintroduced LAP2α into progeria cells they again produced normal ECM and proliferated normally and didn't enter the cellular aging process."
The study's insights why and how progerin impairs the production of ECM proteins and normal proliferation opens new avenues towards the development of more specific therapeutic strategies for the treatment of progeria. As the premature aging disease resembles in many aspects normal aging, the results also allow drawing conclusions on the cellular processes during normal aging.