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Hello everyone. Welcome to SCIEN-SPOT. This podcast shines a spotlight on the latest scientific technology from Japan.
Your host is REN from SCIEN-TALK.
ATPの役割と課題
Today I want to talk about the research achievement concerning the energy factories within your bodies and cells.
This discovery could open up entirely new possibility for extending healthy lifespans in our aging society.
Our bodies need energy for various activities.
Most of this energy is produced by tiny organelles inside our cells called mitochondria.
You can think of mitochondria as small power plants within each of our cells.
It is here that a high-energy molecule called ATP, adenosine triphosphate, often referred to as the body's energy currency, is largely produced and consumed.
Unfortunately, it is known that the function of these vital mitochondria declines with age.
Just as an aging power plant might produce less electricity, a decline in mitochondrial function leads to reduced ATP production, causing dysfunction in various cells and organs.
This is considered one of the fundamental causes of aging and various aging-related diseases.
Developing drugs to restore lowered intercellular ATP levels has been a globally challenging research topic.
This is because administering ATP directly as a drug is difficult due to its low stability in the blood and poor ability to pass through cell membranes, making it hard to deliver effectively into cells.
However, I am thrilled to introduce a revolutionary discovery that addresses this long-standing challenge.
A research team primarily from the Tohoku University has succeeded in developing the world's first nucleic acid blood drug that can efficiently increase intercellular ATP levels.
This compound has been named PRO-X.
You might not be familiar with the term PRO-DRUG.
A PRO-DRUG is a compound designed to be administered to the body and then converted into active drug components through enzymatic reactions.
Imagine a key that doesn't quite fit the cell's keyhole directly.
A PRO-DRUG is like attaching a special handle to that key temporarily.
It allows the key to enter the cell smoothly, and once inside, the handle comes off, allowing the original key to function as intended.
PRO-X is designed with a lipophilic protecting group attached to adenosine monophosphate, AMP,
enabling it to easily close cell membranes and then be converted into necessary adenosine phosphates, AMP, ADP, and ATP inside the cells.
The research team hypothesized that when PRO-X enters the cells, the AMP concentration would temporarily increase,
activating the cell's energy sensor, AMPK.
This is the AMP-activated protein kinase.
AMP acts like an intelligent energy manager.
ATPの増加とエネルギー代謝
When it senses an energy shortage in the cells, it promotes energy production and suppresses energy consumption pathways.
Now let's look at the specific experiment and their amazing results.
First, in experiments using human skin cells, it was confirmed that adding PRO-X led to an increase in intracellular ATP concentration by up to approximately 3 times within 24 hours.
This indicates a shift in the cell's energy metabolism toward a more efficient process called oxidative phosphorylation.
Simultaneously, AMPK was activated without disrupting the cell's energy balance, promoting the efficient use of fatty acids as an energy source.
Furthermore, it was shown that PRO-X suppressed the production of a formal reactive oxygen species, which contributed to aging and disease,
and improved the cell's resistance to oxidative stress, in other words, reducing cellular rust.
It's like the cells are rejuvenating and becoming more resilient to stress.
Next, at the time verified the effects at an organismal level using nematodes, this is C. elegans, which are widely used as model organisms for aging research.
C. elegans are tiny, about 1 mm long, but share many genetic similarities with humans and have a short average lifespan of about 2 to 3 weeks, making them ideal for aging studies.
In this animal-administrated PRO-X, ATP levels indeed increased at the organismal level, the generation of reactive oxygen species was suppressed, and stress tolerance improved.
And the most remarkable result was that the average lifespan of this animal-given PRO-X was extended by a striking 24%, compared to those not given the compound.
To give you an idea, if the same effect could be achieved in humans, it would be like an 80-year-old person living more than 19 years longer, an astonishing number.
Furthermore, direct administration of ATP-AMP, or existing AMPK activator, did not show a lifespan extension effect, clearly demonstrating PRO-X's efficacy as a product and its superiority over existing compounds.
This research breakthrough presents a new possibility to address the fundamental problems of declined energy metabolism associated with aging, which threatens healthy longevity.
This approach of enhancing cellular energy could be a groundbreaking method to extend our healthy lifespan, the period we live in good health, and potentially prevent age-related diseases like Alzheimer's disease or heart disease.
The research team is currently proceeding with verifying the effect of PRO-X in mammal-like mice, and they plan to gather efficacy data in animal models within the next few years.
加齢関連疾患の予防
While there are still various challenges to overcome before practical application, they aim to develop a product that suppress aging and prevent age-related diseases through drug discovery utilizing this technology, and accelerating their research and development with a view toward clinical application in 5-10 years.
I think it's a really high objective. In my opinion, many researchers try this objective and to overcome this limitation of aging.
I think this is very difficult to succeed because aging research is very complicated. But of course, I expect this research is more proceeding.
That's all for today's SciencePod. This podcast is broadcasted daily on weekday morning in both Japanese and English. I'd love for you to listen to the podcast and post your notes and thoughts with the hashtag SciencePod. See you next time.
SciencePod is produced by ESO, the European Southern Observatory.
