Scientists discover new 'drug-like' molecule for anti-aging that keeps cell's 'powerhouse' healthy

Scientists have discovered a new 'drug-like' molecule that seems to slow aging by keeping cells 'powerhouse' healthy.

A Buck Institute in California team identified a compound in plants that boosts a cell’s garbage and recycling center, which declines as we age.

The team tested the bioactive compounds, called Mitophagy-Inducing Compound (MIC), in tiny ringworms, finding their lives extended an average of 20 days, with some living more than 30 days.

MIC achieves its feat in worms by acting on a receptor that humans also have a version of, suggesting that these results could extend to humans. 

Gordon Lithgow, senior co-author, said: 'There’s a bottleneck in efforts to develop potential therapeutics in the field of geroscience, and the bottleneck is that we don’t have enough molecules in the pipeline.

'MIC is a great candidate to bring forward given its therapeutic effect across multiple models and the fact that it is a naturally occurring molecule.' 

Manish Chamoli, PhD, lead author of the study, said that their work shows links between mitophagy, a cell's garbage and recycling center, suggesting that drugs enhancing this process could offer treatment well beyond neurodegeneration or muscle wasting.

The study, published in Nature Aging, found lifespan increased because the worms' mitochondria function improved.

Mitochondria are the powerhouse of the cell - these microscopic parts of cells produce the energy cells need to do their jobs. 

When they don't work, life-threatening diseases can result. Even when they're functioning well, mitochondria can wear out. 

At this point, cells have natural ways of sweeping them away and recycling them in a process called 'mitophagy' - which essentially means 'mitochondria eating.'

As we age, mitophagy slows down, causing a build-up of cellular trash. 

This slowdown is involved in various age-related diseases, including Parkinson's, Alzheimer's, heart failure, obesity, and loss of muscle mass.

There are some ways to give mitophagy a boost, including starvation diets like intermittent fasting, research suggests. 

And studies in mice, worms, and other animals support the idea that periodic or intermittent fasting - followed by a return to normal feeding - can increase lifespans. 

Some existing drugs, too, can restore mitophagy to help fight certain types of cancer, but none are approved to slow aging.  

In the new study, scientists took a new approach.

Looking for a way to encourage mitophagy in a tiny roundworm commonly used in scientific research, they began screening an extensive collection of compounds on nerve cells in dishes to see which ones would boost mitophagy.

One, MIC, 'came up as a major hit,' said Julie Andersen in a statement. 

Andersen, who served as the senior scientist on the study, researches neurodegenerative diseases at the Buck Institute for Research on Aging in Novato, California.

MIC belongs to a class of molecules called coumarins, which occur naturally in cinnamon and tonka beans, among other plants.

'Rather than taking MIC immediately into a mouse model, we wanted to understand its impact on overall aging and identify its mechanism of action,' Andersen said, 'so we took the work into the worm where we found that MIC is in a different class of molecules that enhance the expression of a key protein, TFEB.' 

TFEB is a major contributor to cells' junk-clearing processes. Faulty TFEB production can lead to age-related disorders.

When Andersen and her team gave MIC to worms, it ramped up mitophagy. And in cultured mouse muscle cells, it did the same.

 In the worms, MIC significantly increased lifespans compared to untreated worms.

Mic is 'a promising drug-like molecule,' Andersen and her colleagues write in the study published Monday in the journal Nature Aging.

They found that it does this by working upstream of TFEB by blocking the action of a receptor protein called DAF. 

The human version of DAF, called FXR, regulates TFEB levels in the liver. But it's also present in brain cells - hinting at why MIC acts on TFEB.

'This study provides another piece of the puzzle when it comes to understanding the brain/gut connection in terms of health and disease,' Andersen said. 

Bile salts produced in the gut keep FXR levels in check, so if the microbiome is out of balance, which can happen due to aging, mitophagy can be impacted down the line. 

And since neurons in the brain are maintained by a large number of mitochondria, reduced mitophagy has an outsized effect on brain health.

Ongoing experiments are looking at the role of FXR in Alzheimer's disease. 

MIC is not yet available as a supplement you can take to slow aging, so for now, you're stuck with the basics to support healthy aging: sleep, diet, and exercise.