We now know how a developing embryo reverses signs of ageing and appears younger than the fertilised egg from which it arose. The finding suggests that embryos are able to rejuvenate, which could lead to ways of reversing age-related diseases.
One of life’s great mysteries is how aged parents produce youthful offspring. Our cells show signs of age as a result of the accumulation of damage wrought by the environment and the body’s metabolism, and yet the eggs and sperm our bodies make combine to produce a baby biologically younger than its parents.
This has led biologists to suggest that the germline, the cells that give rise to eggs and sperm and which carry genes down successive generations, are immune to ageing. But recent research shows that not only does the germline age, but that ageing starts even as embryos develop in the uterus, much sooner than we thought.
“Then the question is, if ageing begins earlier, when does it actually begin?” says Vadim Gladyshev at Brigham and Women’s Hospital in Boston.
Age-related damage manifests as changes to patterns of chemical marks, known as methylation, on the DNA in cells’ genomes. These “epigenetic clocks” correlate reliably with chronological age and can be used to track ageing in cells and tissues.
Gladyshev and his colleagues looked at these epigenetic changes in cells and tissues from the start of mouse development. The team found that this measure of ageing began to decrease when the early embryo formed into a hollow ball called a blastocyst and reached its lowest point after it had implanted in the uterus. It then increased again as development progressed.
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The team also looked at data on human embryos, and found signs of a similar pattern at work, although ethical restrictions on growing human embryos beyond 14 days in the lab means the team was unable to study every stage of development.
The discovery points to a rejuvenation mechanism that rolls back ageing to a minimal point from which a new individual can begin life, says Gladyshev.
Ageing can also be reversed in adult cells by reprogramming them into more immature cells known as pluripotent stem cells. However, this also makes the cells lose their specialised adult functions, making it less useful as a way to repair age-related damage. Gladyshev hopes that further study will help reveal whether it is possible to separate these two processes.
“This observation is exciting, since it hints at a potential, naturally occurring rejuvenation that resets the biological time of germ cells during the first days of development,” says Juan Carlos Izpisúa Belmonte at the Salk Institute in La Jolla, California.
Journal reference: bioRxiv, DOI: 10.1101/2021.03.11.435028v1