A transplanted heart seems to take on the biological age of its new body

Is the age of an organ set by the organ itself, or by the body it lives in? Organ transplants are a natural experiment to test this, because donors and recipients often differ in age by decades. A preprint from Brigham and Women’s Hospital and Harvard Medical School suggests the body has the upper hand: a transplanted heart drifts towards the biological age of its new owner.

Measuring “biological age”

Our chronological age is the number of birthdays. Biological age tries to capture how worn the body actually is. One of the best tools for this is an epigenetic clock. DNA carries small chemical tags (methyl groups) that switch genes on or off, and at certain spots on the genome these tags change in a very regular way as we age. A computer model that reads the pattern can estimate age from a tissue sample. If a sample looks older than it is, that tissue is thought to be aging faster. The team used three such clocks, including two “universal” clocks that work across mammals.

In mice: the host sets the clock

The researchers used a standard mouse model in which a second, donor heart is attached to blood vessels in the neck while the mouse keeps its own heart. Donors and recipients were genetically identical, so there was no immune rejection, and they were young (3 months), middle-aged (1 year) or old (about 1.5 years). Four to six months later, they read the clocks in the tissues.

• Young hearts in old mice looked older than their actual age.
• Old hearts in young mice looked younger than their actual age.
• Hearts transplanted between mice of the same age changed less, though the surgery itself seemed to add some biological age.
• The recipients’ own hearts, livers and blood did not clearly change. The effect went one way: from the body to the graft.

Looking beyond the clocks, the methylation changes in young hearts placed in old mice resembled normal aging, and in old hearts placed in young mice they ran in the opposite direction. Gene activity told the same story. The largest shifts were in genes for mitochondria, the cell’s power plants: these were turned down in young grafts in old hosts and up in old grafts in young hosts.

In people: a small but consistent signal

The team then looked at stored heart biopsies from 11 transplant patients, whose donors were between 24 years older and 50 years younger than they were. Hearts from older donors in younger recipients measured younger than the donor’s age, and the reverse for young hearts in older recipients. With the main clocks, the hearts’ biological age tracked the recipient’s age.

In records from a few hundred recipients of the same hospital, one year after transplant, exercise capacity (how much oxygen the body can use at peak effort) was linked to the recipient’s age and not the donor’s.

What to keep in mind

This is a preprint: it has not been through peer review yet. The human biopsy group is very small (11 people), the samples were old archived tissue that is not ideal for this kind of DNA analysis (the authors point this out), and in that group only one of the two universal clocks showed a statistically significant difference. The mouse model differs from a real transplant: the donor heart sits in the neck next to the original heart, and there was no rejection. The heart-function data are associations from medical records, and they cover only the first year.

Why it matters

If confirmed, there are two takeaways. For transplant medicine, older donor hearts, which are often turned down, might do better than expected in younger recipients; the authors say this needs to be tested against real clinical outcomes. For aging research, it supports the idea from experiments that join the blood circulation of young and old animals: the environment an organ lives in, its blood and hormones, strongly shapes how old it acts. It also raises a question for therapies that try to rejuvenate a single organ: will the effect last if the rest of the body stays old?