Mutation provides new insight into the molecular mechanisms of aging

May 5, 2011, Cell Press

A new study identifies the mutation that underlies a rare, inherited accelerated-aging disease and provides key insight into normal human aging. The research, published by Cell Press online May 5 in the American Journal of Human Genetics, highlights the importance of a cellular structure called the "nuclear envelope" in the process of aging.

"Aging is a very complex process which affects most biological functions of an organism but whose remains largely unknown," explains Dr. Carlos López-Otín from the University of Oviedo in Spain. "Over the last few years, our knowledge of the molecular mechanisms underlying human aging has benefited from studies of premature-aging syndromes, such as Hutchinson-Gilford Progeria syndrome, that cause the early development of characteristics normally associated with advanced ."

Previous work has implicated defects in DNA repair systems in human progeria, and more recent studies have also implicated alterations in the . The nuclear envelope is a structure that surrounds the nucleus of a cell. The nucleus houses the cell's genome, and the nuclear envelope interacts with DNA and regulates the exchange of materials, such as transcription factors that control gene expression, into and out of the nucleus. in genes for proteins called "lamins" that form major parts of the nuclear envelope have been linked with progeroid syndromes by this group and others. However, other patients do not exhibit mutations in known candidate genes, suggesting the existence of additional genes implicated in premature aging.

To gain new insight into the molecular mechanisms implicated in accelerated aging, Dr. López-Otín and colleagues sequenced the coding regions of all genes in two unrelated families with a novel progeroid syndrome. This study revealed a mutation in a gene called barrier-to-autointegration factor 1 (BANF1). Both patients had a dramatic reduction in the protein produced by this gene, and their cells exhibited substantial abnormalities in the nuclear envelope. These nuclear defects could be rescued by expression of normal BANF1.

"The finding of mutations in BANF1 associated with a progeroid syndrome may allow the development of therapeutic approaches for patients with this condition, as previously done for other progeroid syndromes," says Dr. López-Otín. "Furthermore, this study underscores the importance of the nuclear lamina for human aging and demonstrates the utility of the new methods of genome sequencing to identify the genetic cause of rare and devastating diseases which have traditionally received limited attention."

Explore further: Scientists create new genetic model of premature aging diseases

Related Stories

Scientists create new genetic model of premature aging diseases

April 29, 2011
Working with a group of national and international researchers, scientists from the Florida campus of The Scripps Research Institute have developed a new genetic model of premature aging disorders that could shed light on ...

Recommended for you

Epigenetics study helps focus search for autism risk factors

January 16, 2018
Scientists have long tried to pin down the causes of autism spectrum disorder. Recent studies have expanded the search for genetic links from identifying genes toward epigenetics, the study of factors that control gene expression ...

Group recreates DNA of man who died in 1827 despite having no body to work with

January 16, 2018
An international team of researchers led by a group with deCODE Genetics, a biopharmaceutical company in Iceland, has partly recreated the DNA of a man who died in 1827, despite having no body to take tissue samples from. ...

Study advances gene therapy for glaucoma

January 16, 2018
While testing genes to treat glaucoma by reducing pressure inside the eye, University of Wisconsin-Madison scientists stumbled onto a problem: They had trouble getting efficient gene delivery to the cells that act like drains ...

The surprising role of gene architecture in cell fate decisions

January 16, 2018
Scientists read the code of life—the genome—as a sequence of letters, but now researchers have also started exploring its three-dimensional organisation. In a paper published in Nature Genetics, an interdisciplinary research ...

How incurable mitochondrial diseases strike previously unaffected families

January 15, 2018
Researchers have shown for the first time how children can inherit a severe - potentially fatal - mitochondrial disease from a healthy mother. The study, led by researchers from the MRC Mitochondrial Biology Unit at the University ...

Genes that aid spinal cord healing in lamprey also present in humans

January 15, 2018
Many of the genes involved in natural repair of the injured spinal cord of the lamprey are also active in the repair of the peripheral nervous system in mammals, according to a study by a collaborative group of scientists ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.