New research from the Howard Hughes Medical Institute reveals that changes in lysosomes – the cellular recycling centers tied to longevity – can be passed from parents to offspring in the roundworm Caenorhabditis elegans (C. elegans).
The work, published in Science, also uncovers a direct connection between lysosomes and the epigenome, showing how environmental adaptations in body cells can influence reproductive cells and persist across generations.
Worms pass longevity clues to multiple descendants
Longevity experiments with C. elegans often produce surprising results. Senior group leader Dr. Meng Wang and her team found that boosting the activity of a lysosomal enzyme extended worm lifespan by up to 60%. Further, offspring of these long-lived worms – despite lacking the genetic modification – also lived longer. When crossed with wild-type worms, their descendants maintained this inherited longevity, with the effect persisting for up to four generations.
In their latest research, Wang and her team uncovered how changes in the worm’s lysosomes that promote longevity are passed from somatic (body) cells to reproductive cells. The key lies in histones – proteins that organize and regulate DNA.
In reproductive cells, these histone messengers modify the worm’s epigenome – the chemical tags that regulate gene expression – allowing lysosomal changes to be inherited without altering the underlying DNA.
“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.”
Epigenetic memory across generations
The team found that one type of histone modification was elevated in long-lived worms compared to those with normal lifespans.
Using genetic tools, transcriptomics and imaging, they showed that changes in lysosomal metabolism activate cellular processes that increase a specific histone variant. This histone travels from body tissues to germline cells through nutrient-delivery proteins. Once inside, the histone is modified, allowing longevity information from the lysosome to enter the germline and be passed to offspring.
They also discovered that fasting triggers this pathway by altering lysosomal metabolism, directly linking environmental stress to germline changes.
The findings add to growing evidence that lysosomes, long viewed as mere recycling centers, act as powerful signaling hubs that influence cellular processes – and even shape future generations. The research also reveals a novel mechanism for transmitting information from soma to germline through histones, which may help explain how other inherited traits arise.
By identifying how environmental changes to somatic cells can be passed through the germline, the study helps clarify previously observed effects, such as how parental malnutrition influences offspring health.
“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.
While the work was carried out in C. elegans, the discovery could have broader implications. Similar epigenetic inheritance has been observed in mammals, where parental diet, stress or toxin exposure can affect offspring health and disease risk. If comparable lysosome–histone communication occurs in humans, it may help explain how environmental factors influence aging and longevity across generations.
Reference: Zhang Q, Dang W, Wang MC. Lysosomes signal through the epigenome to regulate longevity across generations. Science. 2025. doi: 10.1126/science.adn8754
This article is a rework of a press release issued by the Howard Hughes Medical Institute. Material has been edited for length and content.