Tinkering with roundworm proteins offers hope for anti-aging drugs


Date:
July 31, 2020
Source:
The Korea Advanced Institute of Science and Technology (KAIST)
Summary:
Researchers have been able to dial up and down creatures' lifespans
by altering the activity of proteins found in roundworm cells that
tell them to convert sugar into energy when their cellular energy
is running low.

Humans also have these proteins, offering up the intriguing
possibilities for developing longevity-promoting drugs.



FULL STORY ========================================================================== KAIST researchers have been able to dial up and down creatures' lifespans
by altering the activity of proteins found in roundworm cells that
tell them to convert sugar into energy when their cellular energy is
running low. Humans also have these proteins, offering up the intriguing possibilities for developing longevity-promoting drugs. These new findings
were published on July 1 in Science Advances.


==========================================================================
The roundworm Caenorhabditis elegans (C. elegans), a millimeter-long
nematode commonly used in lab testing, enjoyed a boost in its lifespan
when researchers tinkered with a couple of proteins involved in monitoring
the energy use by its cells.

The proteins VRK-1 and AMPK work in tandem in roundworm cells, with
the former telling the latter to get to work by sticking a phosphate
molecule, composed of one phosphorus and four oxygen atoms, on it. In
turn, AMPK's role is to monitor energy levels in cells, when cellular
energy is running low. In essence, VRK- 1 regulates AMPK, and AMPK
regulates the cellular energy status.

Using a range of different biological research tools, including
introducing foreign genes into the worm, a group of researchers led by Professor Seung-Jae V. Lee from the Department of Biological Sciences at
KAIST were able to dial up and down the activity of the gene that tells
cells to produce the VRK- 1 protein. This gene has remained pretty much unchanged throughout evolution.

Most complex organisms have this same gene, including humans.

Lead author of the study Sangsoon Park and his colleagues confirmed that
the overexpression, or increased production, of the VRK-1 protein boosted
the lifespan of the C. elegans, which normally lives just two to three
weeks, and the inhibition of VRK-1 production reduced its lifespan.

The research team found that the activity of the VRK-1-to-AMPK
cellular-energy monitoring process is increased in low cellular energy
status by reduced mitochondrial respiration, the set of metabolic
chemical reactions that make use of the oxygen the worm breathes to
convert macronutrients from food into the energy "currency" that cells
spend to do everything they need to do.

It is already known that mitochondria, the energy-producing engine rooms
in cells, play a crucial role in aging, and declines in the functioning
of mitochondria are associated with age-related diseases. At the same
time, the mild inhibition of mitochondrial respiration has been shown
to promote longevity in a range of species, including flies and mammals.

When the research team performed similar tinkering with cultured human
cells, they found they could also replicate this ramping up and down of
the VRK-1-to- AMPK process that occurs in roundworms.

"This raises the intriguing possibility that VRK-1 also functions
as a factor in governing human longevity, and so perhaps we can start developing longevity- promoting drugs that alter the activity of VRK-1," explained Professor Lee.

At the very least, the research points us in an interesting direction for investigating new therapeutic strategies to combat metabolic disorders
by targeting the modulation of VRK-1. Metabolic disorders involve the disruption of chemical reactions in the body, including diseases of
the mitochondria.

But before metabolic disorder therapeutics or longevity drugs can be contemplated by scientists, further research still needs to be carried
out to better understand how VRK-1 works to activate AMPK, as well as
figure out the precise mechanics of how AMPK controls cellular energy.

This work was supported by the National Research Foundation (NRF),
and the Ministry of Science and ICT (MSIT) of Korea.


========================================================================== Story Source: Materials provided by The_Korea_Advanced_Institute_of_Science_and_Technology_ (KAIST). Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Sangsoon Park, Murat Artan, Seung Hyun Han, Hae-Eun H. Park,
Yoonji Jung,
Ara B. Hwang, Won Sik Shin, Kyong-Tai Kim, Seung-Jae V. Lee. VRK- 1
extends life span by activation of AMPK via phosphorylation. Science
Advances, 2020; 6 (27): eaaw7824 DOI: 10.1126/sciadv.aaw7824 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200731102641.htm

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