Atherosclerosis in Ancient Humans, Accelerated Aging Syndromes and Normal Aging: Is Lamin A Protein a Common Link?

- Atherosclerosis has been observed in ancient human mummies, in an age-related manner.
- The biological factors involved in senile atherosclerosis are poorly understood.
- Aggressive atherosclerosis is observed in diseases with abnormal lamin A.
- Altered lamin A may be involved in the development of arterial pathology in non-Hutchinson-Gilford progeria syndrome settings.

Imaging studies of ancient human mummies have demonstrated the presence of vascular calcification that is consistent with the presence of atherosclerosis. These findings have stimulated interest in the underlying biological processes that might impart to humans an inherent predisposition to the development of atherosclerosis. Clues to these processes may possibly be found in accelerated aging syndromes, such as Hutchinson-Gilford progeria syndrome (HGPS), an ultra-rare disorder characterized by premature aging phenotypes, including very aggressive forms of atherosclerosis, occurring in childhood. The genetic defect in HGPS eventuates in the production of a mutant form of the nuclear structural protein lamin A, called progerin, which is thought to interfere with normal nuclear functioning. Progerin appears to be expressed in vascular cells, resulting in vessel wall cell loss and replacement by fibrous tissue, reducing vessel compliance and promoting calcification, leading to the vascular dysfunction and atherosclerosis seen in HGPS. Interestingly, vascular progerin is detectable in lower levels, in an age-related manner, in the general population, providing the basis for further study of the potential role of abnormal forms of lamin A in the atherosclerotic process of normal aging.