Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Stanford researchers uncover link between 2 aging pathways in mice

09.01.2009
Two previously identified pathways associated with aging in mice are connected, say researchers at the Stanford University School of Medicine.

The finding reinforces what researchers have recently begun to suspect: that the age-related degeneration of tissues, organs and, yes, even facial skin with which we all struggle is an active, deliberate process rather than a gradual failure of tired cells.

Derailing or slowing this molecular betrayal, although still far in the future, may enable us to one day tack years onto our lives — or at least delay the appearance of that next wrinkle.

"There is a genetic process that has to be on, and enforced, in order for aging to happen," said Howard Chang, MD, PhD, associate professor of dermatology at the school and a member of Stanford's Cancer Center. "It's possible that those rare individuals who live beyond 100 years have a less-efficient version of this master pathway, just as children with progeria — a genetic aging disease — may have components of this pathway that are more active."

The study, which will be published in the Jan. 9 issue of Cell, grew out of a three-year collaboration between Chang and Katrin Chua, MD, PhD, assistant professor of endocrinology, gerontology and metabolism at Stanford and member of the Stanford Cancer Center and the Veterans Affairs Palo Alto Health Care System. Chang and Chua are co-senior authors of the research.

The researchers focused their investigation on two seemingly separate pathways linked to aging. One involved a molecule known as SIRT6 — a member of the sirtuin family of proteins that modulate life span in organisms such as yeast and worms — that Chua's laboratory has been studying for several years. She and her lab members have previously shown that SIRT6 is involved in genomic stability and the protection of chromosomal ends called telomeres. Telomeres, which grow shorter with each cell division, are thought to function as a kind of internal molecular clock associated with aging. Furthermore, mice lacking SIRT6 are born normally but die within a few weeks because of a rapid, multi-organ degeneration that somewhat resembles premature aging.

"Sirtuin family members have been implicated in aging and age-related diseases," said Chua, "but very little was known about how SIRT6 worked on a molecular level until recently. Our new study reveals that SIRT6, in addition to its role in genomic stability and telomere protection, also regulates gene expression."

The other pathway involved a more well-known protein called NF-kappa B, or NF-kB, that binds to and regulates the expression of many genes, including those involved in aging. The expression of many of these genes increases with age, and blocking the activity of NF-kB in the skin cells of elderly mice causes them to look and act like younger cells.

The researchers wondered if NF-kB and SIRT6 somehow work together to help cells age appropriately. They found that, in human and mouse cells, SIRT6 binds to a subunit of NF-kB and modifies components of a nearby DNA packaging center, called histones. This modification makes it more difficult for NF-kB to trigger the expression of the downstream gene — perhaps by causing the DNA to twist in such a way to boot off the protein.

"It seems that an important job of SIRT6 is to restrain NF-kB and limit the expression of genes associated with aging," said Chang. "We've been interested in the activity of regulatory genes such as NF-kB during aging for several years now, and we were quite happy to find this very clear biochemical connection between these two pathways."

Young mice lacking the SIRT6 protein displayed elevated levels of NF-kB-dependent genes involved in immune response, cell signaling and metabolism — all potentially involved in the uniformly fatal aging-like condition that killed them within four weeks of birth. Tamping down the expression of the gene for NF-kB's SIRT-binding subunit allowed some of the mice to escape this fate.

"Mice lacking SIRT6 seem to hit some kind of a wall at around four weeks of age," said Chua, "when their blood sugar drops to a level barely compatible with life. Reducing NF-kB activity somehow allows the mice to get over this critical period and to live much longer. These mice provide a great new tool to study the effect of SIRT6-deficiency in much older animals than was possible before."

The researchers are now working to understand how NF-kB knows when and to what extent during an organism's lifetime to initiate the degenerative process and what role SIRT6 may play.

"It's a very provocative question," said Chang. "We've tied together two previously separate pathways in aging. Now we'd like to better understand what regulates that pathway."

Krista Conger | EurekAlert!
Further information:
http://www.stanford.edu

More articles from Life Sciences:

nachricht How molecules teeter in a laser field
18.01.2019 | Forschungsverbund Berlin

nachricht Discovery of enhanced bone growth could lead to new treatments for osteoporosis
18.01.2019 | University of California - Los Angeles

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Ten-year anniversary of the Neumayer Station III

The scientific and political community alike stress the importance of German Antarctic research

Joint Press Release from the BMBF and AWI

The Antarctic is a frigid continent south of the Antarctic Circle, where researchers are the only inhabitants. Despite the hostile conditions, here the Alfred...

Im Focus: Ultra ultrasound to transform new tech

World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles

The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.

Im Focus: Flying Optical Cats for Quantum Communication

Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.

In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...

Im Focus: Nanocellulose for novel implants: Ears from the 3D-printer

Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.

It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:

Im Focus: Elucidating the Atomic Mechanism of Superlubricity

The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.

One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Our digital society in 2040

16.01.2019 | Event News

11th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Aachen, 3-4 April 2019

14.01.2019 | Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

 
Latest News

Additive manufacturing reflects fundamental metallurgical principles to create materials

18.01.2019 | Materials Sciences

How molecules teeter in a laser field

18.01.2019 | Life Sciences

The cytoskeleton of neurons has been found to be involved in Alzheimer's disease

18.01.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>