Premature Aging: Getting Old Too Soon

Topic: Aging Related Conditions
Author: Agency for Science, Technology and Research (A*STAR), Singapore
Published: 2011/01/24 - Updated: 2022/06/24
Contents: Summary - Definition - Introduction - Main - Related

Synopsis: Researchers have produced the first human cell model of progeria, allowing them to make discoveries concerning the mechanism by which aging and progeria work. Hutchinson-Gilford Progeria Syndrome, also known as progeria, is caused by a mutation in the gene encoding for the protein lamin A, an essential component of the membrane surrounding a cell's nucleus. Children with progeria suffer symptoms of premature aging, including growth retardation, baldness, and atherosclerosis (hardened arteries), and many die in their early teens from either heart attack or stroke.

Defining Hutchinson-Gilford Progeria Syndrome (Progeria)

Hutchinson-Gilford Progeria Syndrome (Progeria): Hutchinson-Gilford Progeria Syndrome, also known as Progeria, is a specific type of progeroid syndrome. Progeroid syndromes are a group of diseases that causes individuals to age faster than usual, making them appear older than they are. Children with progeria usually develop the first symptoms during their first few months. Affected children typically look normal at birth and in early infancy but grow more slowly than other children and do not gain weight at the expected rate (failure to thrive). They develop a characteristic facial appearance, including prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and protruding ears. The earliest symptoms may include a failure to thrive and a localized scleroderma-like skin condition. Patients born with progeria typically live to mid-teens or early twenties.

Introduction

Uncovering the trail behind growing too old, too soon - Human model of rare genetic disease reveals new clues to aging process.

Main Digest

Scientists from A*STAR's Institute of Medical Biology (IMB) in Singapore and the University of Hong Kong's Department of Medicine have produced the world's first human cell model of progeria, a disease resulting in severe premature aging in one in four to eight million children worldwide. This model has allowed them to make discoveries concerning how progeria works. Their findings were published this month in the prestigious scientific journal, Cell Stem Cell[1].

Hutchinson-Gilford Progeria Syndrome

Hutchinson-Gilford Progeria Syndrome, also known as progeria, is caused by a mutation in the gene encoding for the protein lamin A, an important component of the membrane surrounding a cell's nucleus. The mutation results in a truncated form of lamin A called progerin, which in turn causes misshapen cell nuclei and DNA damage. Children with progeria suffer symptoms of premature aging, including growth retardation, baldness, and atherosclerosis (hardened arteries), and all die in their early teens from either heart attack or stroke.

Led by IMB's Profs Alan Colman and Colin Stewart, the team used a novel technique of deriving induced pluripotent stem (iPS) cells from cells of human progeria patients[2]. This human progeria model allows the group to trace and analyze the distinctive characteristics of progeria as it progresses in human cells. Previously, only mouse models of the disease were available.

Said Prof Colman:

"While mouse models of progeria have been informative, no one mouse model recapitulates all the symptoms seen in humans. Our human progeria model allows us to examine the pathology of the disease at a much closer resolution than previously possible."

The researchers used their iPS cells to identify two types of cells - mesenchymal stem cells (MSCs) and vascular smooth muscle cells (VSMCs) - that were particularly adversely affected by progeria. This means that a young patient with progeria typically has fewer MSCs and VSMCs than other children. MSCs were found to be very sensitive to a low oxygen environment. Their losses could delay the renewal of the various tissues they gave rise to, thus exacerbating the patient's symptoms of aging. The same effect on VSMCs could explain why their number was reduced in the patient's heart vessels.

Background

The group's findings significantly boost existing research on over ten diseases associated with lamin gene mutations. Prof Stewart previously led a study in mice at IMB showing that progeria affected the connective tissues, potentially via defects in a signaling pathway connecting the nuclear lamina with the extracellular matrix[3] and which was associated with the death of the smooth muscle in major blood vessels.

Said Prof Stewart:

"This new study provides further evidence for the role of lamin processing in connective tissue function, as well as insights into the normal aging process. We hope to find soon new routes of intervention to treat this incurable disease. Such interventions may be useful in treating atherosclerosis in general, a condition afflicting millions of individuals."

References:

[1] A Human iPSC Model of Hutchinson Gilford Progeria Reveals Vascular Smooth Muscle and Mesenchymal Stem Cell Defects. 7 Jan 2011. Cell Stem Cell, Volume x, Issue y. DOI: 10.1016/j.stem.2010.12.002
[2] iPS cells have the potential to differentiate into various cell types found in the body. They are typically made by taking adult (non-differentiating) cells and using viruses to introduce 'reprogramming' genes. iPS cells provide a fast and effective way to study a disease and its progression and screen drug candidates with different cell types.
[3] Functional Coupling between the Extracellular Matrix and Nuclear Lamina by Wnt Signaling in Progeria. Developmental Cell, 2010; 19 (3): 413-425 DOI: 10.1016/j.devcel.2010.08.013

Attribution/Source(s):

This quality-reviewed publication was selected for publishing by the editors of Disabled World due to its significant relevance to the disability community. Originally authored by Agency for Science, Technology and Research (A*STAR), Singapore, and published on 2011/01/24 (Edit Update: 2022/06/24), the content may have been edited for style, clarity, or brevity. For further details or clarifications, Agency for Science, Technology and Research (A*STAR), Singapore can be contacted at a-star.edu.sg. NOTE: Disabled World does not provide any warranties or endorsements related to this article.

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