Key aspects of human cell aging reversed by new compounds

August 7, 2018, University of Exeter
Cellular senescence in human cells. Credit: Eva Latorre

Key aspects of the ageing of human cells can be reversed by new compounds developed at the University of Exeter, research shows.

In a laboratory study of endothelial —which line the inside of blood vessels—researchers tested designed to target mitochondria (the "power stations" of cells).

In the samples used in the study, the number of (older cells that have deteriorated and stopped dividing) was reduced by up to 50%.The Exeter team also identified two (a component of cells) that play a key role in when and how become senescent.

The findings raise the possibility of future treatments not only for blood vessels—which become stiffer as they age, raising the risk of problems including heart attacks and strokes—but also for other cells.

"As human bodies age, they accumulate old (senescent) cells that do not function as well as younger cells," said Professor Lorna Harries, of the University of Exeter Medical School.

"This is not just an effect of ageing—it's a reason why we age.

"The compounds developed at Exeter have the potential to tweak the mechanisms by which this ageing of cells happens.

"We used to think age-related diseases like cancer, dementia and diabetes each had a unique cause, but they actually track back to one or two common mechanisms.

"This research focuses on one of these mechanisms, and the findings with our compounds have potentially opened up the way for new therapeutic approaches in the future.

"This may well be the basis for a new generation of anti-degenerative drugs."

Professor Harries said the goal was to help people stay healthier for longer. She added: "This is about health span and quality of life, rather than merely extending lifespan."

In a paper published last year, the team demonstrated a new way to rejuvenate old cells in the laboratory.

However, the new research looked at precisely targeting and rejuvenating mitochondria in old cells.

Each one of our genes is capable of making more than one product, and splicing factors are the genes that make the decision about which of these products are made.

In this new work, using novel chemicals, the researchers were able to very specifically target two splicing factors (SRSF2 or HNRNPD) that play a key role in determining how and why our cells change with advancing age.

"Nearly half of the aged cells we tested showed signs of rejuvenating into young cell models," said Professor Harries.

The researchers tested three different compounds, all developed at the University of Exeter, and found each produced a 40-50% drop in the number of senescent .

The compounds in question—AP39, AP123 and RT01—have been designed by the Exeter team to selectively deliver minute quantities of the gas hydrogen sulfide to the mitochondria in cells and help the old or damaged cells to generate the 'energy' needed for survival and to reduce senescence.

"Our compounds provide mitochondria in cells with an alternative fuel to help them function properly," said Professor Matt Whiteman, also from the University of Exeter.

"Many disease states can essentially be viewed as accelerated ageing, and keeping mitochondria healthy helps either prevent or, in many cases using animal models, reverse this.

"Our current study shows that splicing factors play a key role in determining how our compounds work."

The research was funded by Dunhill Medical Trust and the Medical Research Council.

The paper, published in the journal Aging, is entitled: "Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2."

Explore further: Old human cells rejuvenated in breakthrough discovery on ageing

More information: Eva Latorre et al, Mitochondria-targeted hydrogen sulfide attenuates endothelial senescence by selective induction of splicing factors HNRNPD and SRSF2, Aging (2018). DOI: 10.18632/aging.101500

Related Stories

Old human cells rejuvenated in breakthrough discovery on ageing

November 7, 2017
A team led by Professor Lorna Harries, Professor of Molecular Genetics at the University of Exeter, has discovered a new way to rejuvenate inactive senescent cells. Within hours of treatment the older cells started to divide, ...

Researchers design a nano-carrier to release drugs into damaged cells

July 27, 2018
Senescent cells are damaged cells that no longer perform their normal roles, but are not dead—hence, they are commonly known as "zombie cells." These cells interfere with the functioning of the tissue in which they accumulate. ...

Rotten egg gas could help protect diabetics from heart complications

September 1, 2016
A gas that was formerly known for its noxious qualities could help people with diabetes recover from common heart and blood vessel complications, concludes research led by the University of Exeter Medical School.

Rotten egg gas holds key to healthcare therapies

July 9, 2014
It may smell of flatulence and have a reputation for being highly toxic, but when used in the right tiny dosage, hydrogen sulfide is now being being found to offer potential health benefits in a range of issues, from diabetes ...

Compound found in berries and red wine can rejuvenate cells, suggests new study

November 15, 2017
By the middle of this century the over 60s will outnumber the under 18s for the first time in human history. This should be good news, but growing old today also means becoming frail, sick and dependent. A healthy old age ...

Recommended for you

Discovery of inner ear function may improve diagnosis of hearing impairment

October 15, 2018
Results from a research study published in Nature Communications show how the inner ear processes speech, something that has until now been unknown. The authors of the report include researchers from Linköping University, ...

Team's study reveals hidden lives of medical biomarkers

October 12, 2018
What do medical biomarkers do on evenings and weekends, when they might be considered off the clock?

Widespread errors in 'proofreading' cause inherited blindness

October 12, 2018
Mistakes in "proofreading" the genetic code of retinal cells is the cause of a form of inherited blindness, retinitis pigmentosa (RP) caused by mutations in splicing factors.

Researchers create a functional salivary gland organoid

October 11, 2018
A research group led by scientists from Showa University and the RIKEN Center for Biosystems Dynamics Research in Japan have, for the first time, succeeded in growing three-dimensional salivary gland tissue that, when implanted ...

Lassa fever vaccine shows promise and reveals new test for immunity

October 11, 2018
Lassa fever belongs to the same class of hemorrhagic fevers as Ebola. Like Ebola, it has been a major health threat in Western Africa, infecting 100,000-300,000 people and killing 5,000 per year. A new vaccine against both ...

Genetically engineered 3-D human muscle transplant in a murine model

October 10, 2018
A growing need for tissues and organs in surgical reconstruction is addressed by the promising field of tissue engineering. For instance, muscle atrophy results from severe traumatic events including deep burns and cancer, ...

4 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

betterexists
1 / 5 (1) Aug 07, 2018
We can only believe if those compounds work on our President, who is 71; May be getting close to 72, Who Knows !
Very good way to prove their point.
tekram
3 / 5 (2) Aug 07, 2018
There is every indication that the president is already undergoing sulfide treatment as evident by his "glistening" appearance at a rally in Ohio over the weekend, where he looked like "C-3PO crossed with a glazed ham."
Moltvic
5 / 5 (1) Aug 07, 2018
We can only believe if those compounds work on our President, who is 71; May be getting close to 72, Who Knows !
Very good way to prove their point.

So brave.
EnricM
not rated yet Aug 08, 2018

So brave.


Yeah, I'm looking forward to the vivisection part. ;)

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.