The deep and difficult problem of aging is intimately linked to the cell nucleus, certainly, but what the linkages are and how they work still stands as an abiding enigma.
What has emerged in recent years, however, is a basket of data about proteins called lamins which, when mutated, seem to play a role – or roles – in the dreadful rapid aging disorder called progeria.
As discovered by Robert Goldman, at Northwestern University in Chicago, the family of lamin proteins is involved in building and probably maintaining a mesh-like network of fibers, the nuclear lamina, that apparently serves as structural scaffolding inside the cell nucleus. Goldman has shown that if this system is disrupted, or made imperfectly, the typical symptoms of advanced aging begin showing up in infants as early as six months of age.
These symptoms include signs of aged skin, loss of subcutaneous fat, abnormal tooth development and loss, joint stiffness and severe circulatory problems. These unfortunate children typically die by age 13, usually as a result of heart attack or stroke.
It is suspected, Goldman said, that the lamina is so important because it serves as a critical platform where the machinery that assembles life’s command molecules – DNA and RNA – can do its work. That offers one potential explanation why the defects typical of progeria strike in so many ways in so many organ systems.
Similarly, Stephen Young, at UCLA, is experimenting with lamins via transgenic mice, looking at a protein-modifying process called farnesylation. Young and his colleagues are trying to assess how farnesylation may be related to causing a dire form of progeria called Hutchinson-Gilford progeria syndrome (HGPS). The Goldman team is also working on this same very rare form of progeria.
Both teams are hoping that data gathered from their work with HGPS will offer clues to how normal aging occurs, but far more gradually, in the elderly human population, as well as hints about how to slow or even reverse the fundamental aging process.