Heart muscle cells rarely divide: Yuri Deigin asks how a young body “dilutes damage” in an old heart

Heart muscle cells rarely divide: Yuri Deigin asks how a young body “dilutes damage” in an old heart

On October 30, biotechnology entrepreneur Yuri Deigin commented on an interview with aging researcher Jesse Poganik. Deigin proposes that signals from the body alter gene activity in a transplanted heart, giving the tissue molecular features associated with the host’s age.

When researchers connected the circulatory systems of an old mouse and a young mouse, molecular signs of aging decreased in the older animal and increased in the younger one. According to Poganik, blood exchange alone did not reproduce all these effects, so the team examined the role of the organs themselves. The authors of a preprint on transplantation transplanted a second heart into mice, leaving each animal’s own heart in place for comparison. After four months, chemical marks on DNA and gene activity indicated that an old heart in a young body had become molecularly younger. By the same measures, a young heart in an old body had become molecularly older.

In the dilution model, a cell grows and synthesizes new molecules before dividing, reducing the proportion of damaged material it contains. That material is then distributed between the daughter cells. The contractile cells of the adult heart rarely divide. Deigin asks:

“What exactly is being diluted when an old heart is placed in a young organism?”

He also asks the converse: what accumulated damage does an old body transfer to a young heart?

In the interview Deigin commented on, Poganik described biological damage as a driver of aging. He explained that harmful substances could enter the heart from an old body. A young environment could lower their concentrations and support damage repair within cells. In this model, the movement of substances into and out of the tissue, together with cellular repair, can alter the condition of existing tissue.

In a separate transplantation study published in 2020, cells that had stopped dividing after damage released mitochondrial DNA. Outside these cells, the DNA triggered an inflammatory response when immune cells detected it through the molecular sensor TLR9. In experiments with immune cells, the response increased with the DNA dose, while equal amounts of DNA from old and young mice elicited similar responses. Blocking TLR9 in mice delayed immune rejection of transplanted hearts from old donors.

This sequence offers two points of intervention: reducing the amount of DNA released or blocking its detection by immune cells. The transfer of molecules and the cellular response they trigger can be successive steps in a single mechanism.