Worms reveal secrets of aging: Researchers discover a conserved pathway that controls aging

October 13, 2017, Case Western Reserve University
Caenorhabditis elegans. Credit: Wikipedia

Investigators at Case Western Reserve University School of Medicine and University Hospitals Health System have identified a new molecular pathway that controls lifespan and healthspan in worms and mammals. In a Nature Communications study published today, researchers showed that worms with excess levels of certain proteins lived longer and healthier than normal worms. In addition, mice with excess levels of these proteins demonstrated a delay in blood vessel dysfunction associated with aging. The study has major implications for our understanding of aging and age-associated disorders.

"We find that by artificially increasing or decreasing the levels of a family of proteins called Kruppel-like transcription factors (KLF), we can actually get these small worms (Caenorhabditis elegans) to live for longer or shorter time periods," said first author Nelson Hsieh, MD/PhD fellow at Case Western Reserve University School of Medicine. "Since this same family of proteins also exists in mammals, what is really exciting is that our data suggests the KLFs also have similar effects on aging in mammals, too."

"The observation that KLF levels decrease with age and that sustained levels of KLFs can prevent the age-associated loss of blood vessel function is intriguing given that vascular dysfunction contributes significantly to diverse age-associated conditions such as hypertension, heart disease, and dementia" added senior author Mukesh K. Jain, MD, Professor, Vice-Dean for Medical Sciences at Case Western Reserve University School of Medicine and Chief Scientific Officer, University Hospitals Health System.

Upon further investigation, the researchers discovered that KLF proteins work by controlling autophagy—a recycling process cells use to clear debris, like misfolded proteins or normal molecular byproducts that build up in old age. Loss of this quality control mechanism is a hallmark of aging.

"As cells age, their ability to perform these functions declines," say the authors. "This likely leads to an unsustainable accumulation of toxic aggregates, which ultimately present an obstacle to cellular survival." Worms without KLF proteins cannot maintain autophagy and die early.

According to the researchers, the next step will be to study the precise mechanisms underlying how autophagy in cells lining blood vessels contributes to improved blood vessel function. They will also seek strategies to target KLF proteins in humans.

Said Hsieh, "As our population ages, we need to understand what happens to our heart and arteries, as we rely on them to function perfectly later and later on in our lives. Our findings illuminate what can happen during aging, and provide a foundation to designing interventions which slow these processes."

Explore further: Fast-forward aging due to DNA damage

More information: Paishiun N. Hsieh et al, A conserved KLF-autophagy pathway modulates nematode lifespan and mammalian age-associated vascular dysfunction, Nature Communications (2017). DOI: 10.1038/s41467-017-00899-5

Related Stories

Fast-forward aging due to DNA damage

August 30, 2017
The heredity substance DNA is the blueprint of our life. Like an instruction manual it contains all the information needed for cells and the body to function properly. In the process, the DNA is always exposed to threats ...

When heavy metals go off-kilter: Study in C. elegans shows excess iron promotes aging

January 15, 2015
It's been known for decades that some metals, including iron, accumulate in human tissues during aging and that toxic levels of iron have been linked to neurologic diseases, such as Parkinson's. Common belief has held that ...

Protein aggregates save cells during aging

May 8, 2015
As an organism ages, a gradual loss of cellular protein quality control occurs. This results in the increased production of toxic protein clumps, so-called aggregates. Using a comprehensive approach, researchers in the teams ...

Fine-tuning cellular energy increases longevity

February 25, 2016
In new research from the Sanford Burnham Prebys Medical Discovery Institute (SBP), scientists have identified a protein that can extend the natural lifespan of C. elegans, a microscopic roundworm commonly used for research ...

For the first time, researchers reveal a causal link between RNA splicing and aging

December 5, 2016
Aging is a key risk factor for a variety of devastating, chronic diseases, yet the biological factors that influence when and how rapidly cells deteriorate over time remain largely unknown. Now, for the first time, a research ...

Dietary restriction increases lifespan through effects on the gut

July 14, 2016
Dietary restriction, or limited food intake without malnutrition, has beneficial effects on longevity in many species, including humans. A new study from the Sanford Burnham Prebys Medical Discovery Institute (SBP), published ...

Recommended for you

Gene plays critical role in noise-induced deafness

October 19, 2018
In experiments using mice, a team of UC San Francisco researchers has discovered a gene that plays an essential role in noise-induced deafness. Remarkably, by administering an experimental chemical—identified in a separate ...

Functional engineered oesophagus could pave way for clinical trials 

October 18, 2018
The world's first functional oesophagus engineered from stem cells has been grown and successfully transplanted into mice, as part of a pioneering new study led by UCL.

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

Income and wealth affect the mental health of Australians, study shows

October 16, 2018
Australians who have higher incomes and greater wealth are more likely to experience better mental health throughout their lives, new research led by the Bankwest Curtin Economics Centre has found.

4 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

betterexists
not rated yet Oct 14, 2017
What is wrong in courting Immortality?
Also, Biological Research too should go full-speed like other fields.
Take for example, unicellular Euglena that both act like plants & also eat/devour like animals.
They can live in both fresh water and salt water.
They have to convert Amoeba too in Lab to Photosynthesize like Euglena!
Since we cannot tinker safely and properly with human bodies.....We should start with tiny ones for the present.
betterexists
not rated yet Oct 14, 2017
What is wrong in courting Immortality?
Also, Biological Research too should go full-speed like other fields.
Take for example, unicellular Euglena that both act like plants & also eat/devour like animals.
.
https://euglenapr...ess.com/
betterexists
not rated yet Oct 14, 2017
What is wrong in courting Immortality?
Also, Biological Research too should go full-speed like other fields.
Take for example, unicellular Euglena that both act like plants & also eat/devour like animals.
.
https://euglenapr...ess.com/ Euglena eats green algae, amoebae, paramecia and rotifers.
https://www.refer...11a7046e
betterexists
not rated yet Oct 15, 2017
Research to make People/Any Living Being Immortal is like climbing Long Stairs. 1st step HAS TO BE TAKEN. Amoebae are unicellular, The "Giant Amoebae", Chaos carolinense & Amoeba proteus, "Brain-eating amoeba" Naegleria fowleri, Intestinal parasitic Amoeba Entamoeba histolytica, HARMLESS Entamoeba coli, Entamoeba dispar, and Entamoeba hartmanni etc., With Great Gene Editing Tool, Already in our hands, WHY NOT FIND A VIRUS that can get into these and convert them from one into the other, carrying the needed genes?
IT HAS TO BE, SHOULD BE DONE! A MUST. How stupid it is! Even today Humans keep dying in the hands of feline cats, crocs, whales, sharks, bears etc., REMOVE THEM ASAP ! We have tools today to deal with the consequences later on!

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.