The Inherited Secret of Longevity: How Lysosomes Rewrite the Rules of Genetics

If you’ve ever been interested about reproduction or inheritance, you probably think that the DNA is the sole messenger for genetic traits. That’s not completely wrong, but recently, a group of scientists in Virginia discovered that the trait of longevity can be passed down without the alteration of DNA but with chemical signals inside cells. The key lies in lysosomes, which were thought to be merely the cell’s recycling site.

In the Wang Lab at HHMI's Janelia Research Campus, they found that increases in the activity of an enzyme in lysosomes of roundworm C. elegans can allow them to live up to 60% longer than usual. Moreover, when alteration ceased, their offsprings still lived longer than usual. And even when bread with un-altered worms, a common method used to remove any genetic manipulation, their descendants continued to show extended lifespans.

In their latest studies, they investigated how these life-extending traits are passed down. They found that the lysosomal changes are communicated from the body cells to the reproductive cells through histones, a protein that is used to organize DNA. Histones will then alter the worm’s genetic chemical markers called epigenome, allowing the trait to be inherited without involving the DNA.

To look into the specific process of histone modification, researchers used advanced genetic tools, imaging, and gene expression analysis. They realized that the process is triggered by an alteration in lysosomal metabolism, which increases a specific histone variant travelling to its reproductive cells. This is done through a protein that normally delivers nutrients to eggs. Once in the reproductive cells, the histones undergo chemical modification, giving out lysosomal information for inheritance. Furthermore, it is found that this pathway is related to fasting, a natural form of altering lysosomal metabolism, connecting a physical state to an inheritable chemical adjustment.

Overall, these results further established lysosome’s purpose in the cell, it is no longer only the recycling center, but also help regulate cell processes, such as trait inheritance in this case. The study also reveals a previously unknown source of information exchange through histones, which can help explain how other changes are passed down generations in a family. It also provides valuable insights into transgenerational effects like how parental malnutrition can impact offsprings.