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 Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>