Uncovering the trail behind growing too old, too soon

Jan 24, 2011

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 ageing in one in four to eight million children worldwide. This model has allowed them to make new discoveries concerning the mechanism by which progeria works. Their findings were published this month in the prestigious scientific journal, Cell Stem Cell(1).

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 and . Children with progeria suffer symptoms of premature ageing, 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) from cells of human progeria patients. This human progeria model allows the group to trace and analyse the distinctive characteristics of progeria as it progresses in . Previously, only mouse models of the disease were available.

Said Prof Colman, "While mouse models of progeria have been informative, no one 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 (MSCs) and vascular smooth muscle cells (VSMCs) – that were particularly adversely affected by progeria. This means that a young patient with progeria would typically have fewer MSCs and VSMCs than other children. MSCs were found to be very sensitive to a low oxygen environment and their losses could delay renewal of the various tissues they gave rise to, thus exacerbating the patient's symptoms of ageing. The same effect on VSMCs could explain why their number was reduced in the patient's heart vessels.

Background

The group's findings are a significant boost to existing research on over 10 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 (2) and which was associated with 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 ageing process. We hope to soon find new routes of intervention to treat this incurable disease. Such interventions may be of use in treating atherosclerosis in general, a condition afflicting many millions of individuals."

Explore further: US scientists make embryonic stem cells from adult skin

More information: 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) 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

Provided by Agency for Science, Technology and Research (A*STAR)

not rated yet
add to favorites email to friend print save as pdf

Related Stories

New insight into 'accelerated aging' disease

Sep 13, 2010

Hutchinson-Gilford Progeria Syndrome (HGPS or progeria) is a rare genetic disease that causes young children to develop symptoms associated with advanced age, such as baldness, wrinkles, osteoporosis and cardiovascular disease. ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

Less-schooled whites lose longevity, study finds

Barbara Gentry slowly shifts her heavy frame out of a chair and uses a walker to move the dozen feet to a chair not far from the pool table at the Buford Senior Center. Her hair is white and a cough sometimes interrupts her ...

How to keep your fitness goals on track

(HealthDay)—The New Year's resolutions many made to get fit have stalled by now. And one expert thinks that's because many people set their goals too high.

Low tolerance for pain? The reason may be in your genes

Researchers may have identified key genes linked to why some people have a higher tolerance for pain than others, according to a study released today that will be presented at the American Academy of Neurology's 66th Annual ...

Growing app industry has developers racing to keep up

Smartphone application developers say they are challenged by the glut of apps as well as the need to update their software to keep up with evolving phone technology, making creative pricing strategies essential to finding ...

Making graphene in your kitchen

Graphene has been touted as a wonder material—the world's thinnest substance, but super-strong. Now scientists say it is so easy to make you could produce some in your kitchen.