Meng Wang, Senior Group Leader at HHMI's Janelia Research Campus, and her team investigate the biology of longevity. They've found that when they boost the activity of a certain enzyme inside the lysosomes of the roundwormC. elegans, the animals can live up to 60 percent longer than usual.

What caught the scientists off guard was what happened next. Even when the genetic alteration was removed, the offspring of these long-lived worms still lived longer than normal. When the team bred the modified worms with unaltered "wild-type" worms (a common method used to remove any genetic manipulation), their descendants continued to show extended lifespans -- lasting several generations.

Passing Longevity Through the Generations

In their latest study, Wang's group discovered how these life-extending traits are passed down. The key lies in lysosomes, which were once thought to be little more than the cell's recycling centers. The researchers found that lysosomal changes linked to longevity are communicated from body cells to reproductive cells through histones -- proteins that help organize and regulate DNA.

Once in the reproductive cells, these histones alter the worm's epigenome (a set of chemical markers that control gene activity), allowing the lysosomal effects to be inherited without changing the DNA itself.

Inheritance Beyond DNA

The discovery could have implications far beyond lifespan. Epigenetic changes help organisms adjust to shifts in diet, toxins, or stress, and Wang's work shows how these adaptations might be passed from parent to offspring.

"You always think that your inheritance is in the nucleus, within the cell, but now we show that the histone can go from one place to another place, and if that histone carries any modification, that means you are going to transfer the epigenetic information from one cell to another," Wang says. "It really provides a mechanism for understanding the transgenerational effect."

Tracking the Path of Inheritance

The researchers identified a specific histone modification that was more common in long-lived worms than in those with typical lifespans. They wanted to understand how this change connected to the lysosomal shifts that promote longevity.

Through advanced genetic tools, imaging, and gene expression analysis, they traced a chain of cellular events triggered by altered lysosomal metabolism. These processes increase a particular histone variant, which travels from the worm's body cells to its germline (reproductive cells). The transport happens through proteins that normally deliver nutrients to developing eggs. Once inside the germline, the histone is chemically modified, allowing lysosomal information to enter the reproductive line and be inherited.

When Fasting Activates the Process

The team also discovered that this pathway becomes active during fasting, which naturally alters lysosomal metabolism. This finding connects a physical state -- such as a change in diet -- to inheritable cellular adjustments in the germline.

Wang's results add to a growing recognition that lysosomes are not merely recycling hubs. They act as critical signaling centers that help regulate many processes in the cell, and in this case, influence traits across generations.

A Bridge Between Generations

The study also reveals a previously unknown way that information moves between body and reproductive cells through histones. This process could help explain how other environmental or physiological changes are passed down through families.

By showing how alterations in body cells can influence the germline, the research provides insight into long-observed transgenerational effects -- such as how parental malnutrition can impact children and grandchildren.

"We now show that the soma and the germline can be connected by the histone and can carry memorable genetic information for generations," Wang says.

Key Results

• New research in the roundwormC. elegans shows how changes in the parent's lysosomes that promote longevity are transferred to its offspring.
• The work describes a new link between lysosomes -- cellular organelles once thought to be the cell's recycling center -- and the epigenome -- a set of chemical marks that modify gene expression. The study also details a new way that epigenetic information is transmitted from cells in the body to reproductive cells, allowing changes to be inherited without affecting the genetic code.
• These insights show how epigenetic modifications that help organisms cope with environmental stress can be conferred from parents to their offspring.

• RELATED TOPICS
  • Health & Medicine
    • Diet and Weight Loss
    • Healthy Aging
    • Genes
    • Epigenetics
  • Plants & Animals
    • New Species
    • Molecular Biology
    • Cell Biology
    • Biotechnology and Bioengineering

• RELATED TERMS
  • DNA
  • Biology
  • RNA
  • Evolution
  • Introduction to genetics
  • Telomere
  • Limbic system
  • Gene therapy