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The good, the bad and the ugly: the roles of different vascular cell types in premature aging

In a new review article in the scientific journal Trends in Molecular Medicine, AIAS Fellow Magda R. Hamczyk and collaborators shed light on the roles of different vascular cell types in progeria, an accelerated-aging disease.

Image: A schematic representation of an artery wall with an atherosclerotic plaque. Key cell types involved in the initiation and progression of vascular disease (endothelial cells, smooth muscle cells and myeloid cells) are indicated.

Aging is unequivocally linked to vascular function decline, which leads to cardiovascular events such as strokes and heart attacks. Nonetheless, a remarkable variability between individuals exists in the onset and severity of vascular disease. Hence, studying the conditions that speed up or slow down the aging process in our blood vessels might provide hints on how to preserve health.

Learning from accelerated aging

Diseases that feature premature aging are therefore a unique opportunity for the research community to expand our knowledge in this aspect. Hutchinson-Gilford Progeria Syndrome (HGPS or progeria) is an example of such diseases. It is caused by a genetic mutation leading to the production of an aberrant protein called progerin that accelerates aging, especially in the cardiovascular system. Progeria patients typically die before reaching adulthood from cardiovascular disease-related causes. It is reported that low amounts of this toxic protein progerin are also produced during normal aging which suggests that findings on progeria may also be relevant for the general population.

Recent studies – recent advancements

In recent published studies, AIAS-AUFF fellow Magda Hamczyk and international colleagues have addressed the roles of different cell types in the development of cardiovascular disease linked to progeria (doi: 10.1073/pnas.2400752121, doi: 10.1161/CIRCULATIONAHA.123.065768, and doi: 10.1111/acel.14389; see also here). 

In a new review article entitled “Vascular cell types in progeria: victims or villains?” published in the journal Trends in Molecular Medicine, Magda Hamczyk and colleagues discuss recent advances in the understanding of premature vascular disease and aging linked to progeria, with special emphasis on the role of smooth muscle and endothelial cells.

Smooth muscle cell damage – victims and villains

The key take home message is that the smooth muscle cell damage appears to be an initial trigger for the accelerated vascular disease in progeria. This damage sets off a chain of events in other cell types of the blood vessel wall, leading to vascular disease progression and its life-threatening complications. In this way, smooth muscle cells are both the "victims" of progerin’s toxic effects and the "villains" that spread harm to nearby cells.

Remarkably, in response to smooth muscle alterations, endothelial cells seem to change their fate. Such surprising plasticity in cardiovascular tissues merits further mechanistic studies. In her project at AIAS, Magda Hamczyk is currently working on addressing those mechanisms of cellular re-programming and their potential implications.

Access the review article here

‘Vascular cell types in progeria: victims or villains?’ in: Trends in Molecular Medicine by Ignacio Benedicto, Magda Hamczyk et al, April 2025.

Read the article here

Contact

Magda R. HamczykAIAS-AUFF Fellow
E-mail: mhamczyk@aias.au.dk

Aarhus Institute of Advanced Studies, AIAS
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