Reducing Lamin A Protein. A Cure For Aging?

Everyone gets emails touting anti-aging solutions from skin creams to vitamin supplements, and it is difficult to know for decades whether any of these work. They may have temporary effects, but they are all designed for you to keep taking them - good for business.

Certainly reducing free radicals by boosting antioxidants helps. Avoiding carcinogenic activities like too much exposure to the sun, smoking tobacco, avoiding contact with chemicals ending in "-ium" can help, but these do not get at why we really age.

There is an interesting blog on why we age at: http://hubpages.com/hub/Why-do-we-age. This blog lists a number of aging related causes, but leaves out perhaps the single biggest one, the buildup of a protein, called Lamin A. 

The surface of the cell nucleus of our cells is a porous structure called the lamina. Inside the lamina is our DNA, all mangled up like a bowl of spaghetti. The openings of the lamina meshwork allow proteins, mRNA and other molecules to pass in and out of the nucleus. Our lamina is made up of two proteins, Lamin A and Lamin C. 

As we age, Lamin A is continually produced by our bodies, and over time, it builds up on the lamina, causing it to shrivel like a raisin. In microcosm, it resembles a porous raisin, but in aggregation, it shows up as wrinkles in our skin and is a chief contributor as to why we shrink when we age.

There may be an even greater concern with this lamin A buildup. As the lamina shrinks, some scientists believe it may cause pressure on our double helical DNA, resulting in damage. When we have DNA damage, often a strand of DNA breaks and flaps around, until one of our 700 DNA damage repair proteins repairs the breakage. However, if it is, indeed, the case that shrinking lamina causes excess DNA damage, it may be too much for our DNA damage repair proteins to keep up with the repair, which could help lead to the many diseases of aging. 

In May, 2006, a published study showed that when the lamin A protein was inhibited in aged mice, not only did the shriveling of their lamina cease, but their lamina became plump again. OK, if this works in humans, and there are no off-target effects of reducing lamin A production, we have a valuable solution to wrinkling. However, more importantly, if it's true that shrinkage of the lamina contributes significantly to DNA damage, we may have reduced the incidence of age related diseases, since the shrinking lamina would no longer be putting pressure on our DNA.

For more info on this see: http://tinyurl.com/qldqth

How can this cure for aging be properly put to the test? One thought has been to establish a clinical trial for patients with the disease progeria, a childhood disorder that rapidly accelerates aging, where people with this disorder rarely live past their 20's, at which point they appear to be in their 80's or 90's. It's not clear this would work, since progeria is a different disorder of the lamina where cytosine is replaced by thymine in position 1824 of the LMNA gene. 

See: http://en.wikipedia.org/wiki/Progeria

However, perhaps there will be a gene therapy to fix this disorder in people with progeria. It is highly unlikely simply reducing the production of lamin A protein will alter the cytosine/thymine issue.

The difficulty with reducing or inhibiting (knocking down) the production of lamin A protein on normal healthy people is that the results would not be known for decades, unless it is tried on older people. Certainly, if it works on older people, wrinkles should reduce or disappear quickly. Also, if the theory is correct that shrinkage of the lamina results in more damage to the DNA, then this group of trials should show a reduction in the diseases associated with aging. It would be interesting to know if the effect on mice would be similar to those on humans.

For more info on Lamin A and the gene LMNA, see: http://ghr.nlm.nih.gov/gene=lmna