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Aging in the Cardiovascular System: Lessons from Hutchinson-Gilford Progeria Syndrome
Magda R Hamczyk1,2, Lara del Campo1,2, Vicente Andrés1,2
1Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain;
Insights
Aging significantly increases cardiovascular disease (CVD) risk. Research on Hutchinson-Gilford progeria syndrome (HGPS) reveals mechanisms linking progerin to accelerated aging and CVD, offering insights into normal aging processes.
Area of Science:
- Cardiovascular Science
- Aging Research
- Genetics
Background:
- Aging is the primary risk factor for cardiovascular disease (CVD).
- Hutchinson-Gilford progeria syndrome (HGPS) accelerates aging and CVD due to a progerin mutation.
- Atherosclerosis and heart failure are major contributors to age-related CVD mortality.
Purpose of the Study:
- To understand how aging promotes cardiovascular disease.
- To explore mechanisms of accelerated aging and CVD in HGPS.
- To identify potential therapeutic targets for age-related CVD.
Main Methods:
- Review of structural and functional cardiovascular changes in physiological and premature aging.
- Discussion of mechanisms involving prelamin A and progerin in CVD.
- Analysis of HGPS as a model for studying normal aging processes.
Main Results:
- Progerin causes severe atherosclerosis and cardiac electrophysiological alterations in HGPS.
- HGPS exhibits hallmarks of normal aging, suggesting shared underlying mechanisms.
- Pre-lamin A and progerin contribute to cardiovascular aging in both HGPS and normal aging.
Conclusions:
- Understanding HGPS mechanisms can illuminate pathways of physiological cardiovascular aging.
- Targeting progerin-related pathways may offer strategies to mitigate age-associated CVD.
- Further research into prelamin A and progerin is crucial for developing interventions against CVD and aging.
Abstract:
Aging, the main risk factor for cardiovascular disease (CVD), is becoming progressively more prevalent in our societies. A better understanding of how aging promotes CVD is therefore urgently needed to develop new strategies to reduce disease burden. Atherosclerosis and heart failure contribute significantly to age-associated CVD-related morbimortality. CVD and aging are both accelerated in patients suffering from Hutchinson-Gilford progeria syndrome (HGPS), a rare genetic disorder caused by the prelamin A mutant progerin. Progerin causes extensive atherosclerosis and cardiac electrophysiological alterations that invariably lead to premature aging and death. This review summarizes the main structural and functional alterations to the cardiovascular system during physiological and premature aging and discusses the mechanisms underlying exaggerated CVD and aging induced by prelamin A and progerin. Because both proteins are expressed in normally aging non-HGPS individuals, and most hallmarks of normal aging occur in progeria, research on HGPS can identify mechanisms underlying physiological aging.