Germline cells seem to reset their biological clocks around the time of embryo implantation, not when generating gametes, as previously thought.
Scientists measured an increase in genetic damage in embryonic cells during the early stages of embryogenesis in mice before undergoing a total reset within a 'rejuvenation period', reversing any cell damage.
'This study uncovers a natural rejuvenation event during embryogenesis and suggests that the minimal biological age (ground zero) marks the beginning of organismal ageing,' wrote the researchers from Harvard Medical School and Brigham and Women's Hospital in Boston, Massachusetts.
Previously, it was thought that, unlike the somatic cells which form our bodies, germline cells – which differentiate into either sperm or eggs – were ageless and did not inherit genetic damage from their parent organisms. However, recent research has shown that germline cells do age and display hallmarks of genetic damage. Yet, babies do not inherit their parents' age, and start again from zero.
The team employed machine-learning algorithms as 'ageing clocks' to calculate the ages of human and mouse embryonic tissue by measuring the prevalence of methylation – an epigenetic marker. These markers accumulate with age on certain sections of DNA and are influenced by environmental factors. Although these markers do not affect the DNA sequence, they can alter the way a gene is expressed and modify proteins produced.
Genetic data sets collected from mouse embryos during different stages of embryonic development were analysed by these epigenetic ageing clocks. Data sets recorded from mouse embryos following fertilisation showed increased epigenetic ageing with time during the first six days of cell division. But, during its implantation within the uterus wall, the embryonic cells displayed a decrease in epigenetic damage, characteristic of a reversal in ageing.
The team were unable to perform the same experiment in human embryos but were able to compare methylation in human induced pluripotent stem cells and embryonic stem cell lines and datasets detailing methylation in human fetal tissue samples and see that a similar reset appeared to have occurred.
The findings, published in the journal Science Advances, have wide-reaching implications for aiding the treatment of age-related illnesses such as Alzheimer's and Parkinson's disease. These diseases feature cells with accelerated epigenetic ageing and through a greater understanding of these biological reset mechanisms, it is thought that epigenetic damage to these cells could be reversed. However, achieving this in practice may be challenging since knowledge of other causes of cellular ageing is needed.