A recycling mechanism that helps cells fight aging

Aging is a fact of life. As we get older, our bodies and minds change, and our bodies become susceptible to a number of age-related diseases. As a result, a major focus of scientific research today is finding ways to slow or even reverse aging.

One of the challenges is understanding how our cells deal with waste and damage. As cells age, their ability to clean up toxic proteins and broken components declines. This buildup is linked to a range of health problems, from loss of mobility to serious illnesses like Alzheimer’s disease.

Valuable help

Now, an international team of scientists led by Johan Auwerx at EPFL has discovered a defense system in the common worm Caenorhabditis elegans that helps cells clear out harmful waste.

The system is called Lysosomal Surveillance Response (LySR), and switching it on boosts the activity of lysosomes, the cell's organelles responsible for breaking down and recycling waste. Activating LySR made the worms live about 60% longer, and also helped protect them from toxic protein clumps that cause neurodegenerative diseases, like Alzheimer’s and Huntington’s disease.

The research was a collaboration of EPFL with Fudan University (China), Amsterdam UMC (the Netherlands), and Baylor College of Medicine (US). The findings are published In Nature Cell Biology.

The superpowers of the LySR defense system

The team discovered the LySR pathway while studying what happens when certain waste-disposal genes are switched off. They then turned off a group of genes that make tiny pumps called vacuolar H+-ATPase subunits, which help lysosomes work. The result was fascinating: they unexpectedly activated the LySR pathway in the cell.

The researchers also found that LySR is controlled by the ELT-2 gene, which acts as a master switch for the cell’s clean-up system. After turning on LySR, they tracked how well the worms could clear out protein build-up, how long they lived, and how well they resisted signs of aging and disease.

To confirm the effect the scientists tested LySR activation in several different worm models of neurodegenerative diseases like Alzheimer’s and Huntington’s disease. They found that the LySR pathway consistently improved cellular health and waste clearance, which helps to “detox” the cells.

While the research was carried out in worms, similar pathways to LySR exist in humans, raising hope for new approaches to healthy aging and treating neuro-degenerative disease.