Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer drug prolongs life in flies

29.06.2015

Trametinib inhibits the same signal pathway in flies and humans and could thus conceivably also extend life expectancy in humans

Humans, yeasts and fruit flies began to evolve separately millions of years ago. Nevertheless, the cellular processes which regulate cell division and cell death – and therefore the mechanism of ageing – are similar in all of them. Scientists at the Max Planck Institute for Biology of Ageing in Cologne and University College London have now succeeded in controlling this mechanism, thus extending life expectancy in fruit flies by around twelve percent.


Older fruitfly (Drosophila melanogaster).

© Nazif Alic

They achieved this with the help of a cancer drug called Trametinib. Human cells contain the same molecular switches that Trametinib targets in fruit flies. It is therefore conceivable that the substance could be used to develop future anti-ageing drugs to extend life expectancy in humans.

To ensure a long and healthy life in humans, researchers have to understand the ageing process at the cellular level more precisely. A scientific study has now shown how Ras proteins can be manipulated to prolong the lifespans of animals.

Ras proteins play a key role in the regulation of cell processes. As molecular switches within the cellular signalling network, they control vital functions such as cell division, cell death, specialisation and metabolism. They regulate these intracellular processes via the Ras-Erk-ETS signal pathway. This network has been conserved over hundreds of millions of years of evolution and is present in single-cell organisms such as yeasts, in insects such as the fruit fly (Drosophila), as well as in mammals such as mice and humans.

It was already known that inhibition of this signal pathway can prolong the life expectancy of yeast cells. However, to achieve this, the scientists had thus far manipulated the DNA directly in order to deactivate individual genes and with them the Ras signal pathway. However, no substance was known that could slow the ageing process at this interface. Recent work by the research team has now filled this gap.

The scientists took advantage of the fact that the Ras-Erk-ETS signal pathway has been thoroughly researched in the context of cancer treatment. This is because overactivation of Ras is carcinogenic: in around a third of cancer patients, the Ras proteins of cancer cells are mutated, resulting in uncontrolled cellular division. Many cancer researchers have therefore focussed on this signal pathway - and the first drugs have already been developed to interfere with Ras signalling in order to check cancerous growth.

The researchers administered one of those substances, Trametinib, to fruit flies in the form of a food additive. Even a small dose, which is approximately equivalent to a daily dose of the drug in a human patient, increased the fruit flies’ average life expectancy by eight percent. With a moderate dose, the flies lived twelve percent longer on average.

Any drug suitable for anti-ageing applications must be effective even if it is administered during an advanced phase of life. The scientists successfully demonstrated this property. In a substudy, they administered the substance for the first time to Drosophila that were 30 days old – a ripe old age for this species. At this point, egg laying, i.e. the insects’ fertile phase, has ceased. Even when a moderate dose of the substance was given to the flies at this late point in their lifespan, it still increased their average life expectancy by seven percent. The researchers observed no adverse effects on the insects’ digestive system or food intake.

“Our findings indicate what substance classes could be used to slow the ageing process in humans,” explains Nazif Alic of University College London. “The Ras-Erk-ETS signal pathway could serve as a target for those substances.” The aim now is to investigate this pathway more closely. “The study suggests that inhibition of this signal pathway has positive effects on longevity and mortality,” says Cathy Slack, who researches at University College London and at the Max Planck Institute for Biology of Ageing. Slack emphasises that Trametinib has been approved by the FDA as a drug for the treatment of skin cancer and is therefore already in clinical use.

In mammals, Ras acts as a mediator for the insulin/IGF-1 signal pathway, which modulates life expectancy. Ras activation has effects on both the PI3/Akt and Erk/Mapk signal pathways. Until now, it was assumed that the PI3/Akt branch is primarily responsible for modulating lifespan. The findings show, however, that the Erk branch is also important in this regard. Two transcription factors controlled by Ras-Erk appear to be key mediators of these effects: Pnt, a gene expression activator, and Aop, a repressor. It therefore appears likely that life expectancy can be regulated via both branches of the signal pathway.


Contact

Prof. Dr. Linda Partridge
Max Planck Institute for Biology of Ageing, Köln
Phone: +49 221 37970-602

Email: Christine.Lesch@age.mpg.de

Scientific and Personal Assistance:
Dr. Christine Lesch


Original publication
Cathy Slack, Nazif Alic, Andrea Foley, Melissa Cabecinha, Matthew P. Hoddinott, and Linda Partridge

The Ras-Erk-ETS signalling pathway is a drug target for longevity

Cell; 25 June, 2015

Prof. Dr. Linda Partridge | Max Planck Institute for Biology of Ageing, Köln
Further information:
http://www.mpg.de/9294150/trametinib-longevity

More articles from Life Sciences:

nachricht Cnidarians remotely control bacteria
21.09.2017 | Christian-Albrechts-Universität zu Kiel

nachricht Immune cells may heal bleeding brain after strokes
21.09.2017 | NIH/National Institute of Neurological Disorders and Stroke

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

Cnidarians remotely control bacteria

21.09.2017 | Life Sciences

Monitoring the heart's mitochondria to predict cardiac arrest?

21.09.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>