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 What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>