The earliest moments of embryo development have a measurable impact on a person’s future health and ageing, according to a new study from the University of Adelaide in South Australia.
From the moment of conception, our cells begin to write the blueprint of our future. One key element in this script is the telomere — a protective cap made of DNA and proteins on the end of each chromosome. Over time, telomeres wear down in a process that is linked to chronic diseases and aging.
It is known that the initial setting of telomere length during early life has a major influence on the risk of aging-associated diseases, but there is limited knowledge about biological signals that determine the inheritance of telomere length.
“As just one example shorter telomeres are observed in children of women with obesity or metabolic syndrome,” says biomedical scientist from Adelaide University, Professor Rebecca Robker.
“As adults, these individuals are at increased risk of premature mortality from cardiovascular events, like a heart attack or stroke, even when they are not obese themselves.
“Until now it has not been clear how the length of telomeres is determined before birth.”
Robker is leading a team at Reproduction and Development, School of Biomedicine, Robinson Research Institute examining the relationship between embryo growth and aging. They conducted a pre-clinical trial and found that cellular processes within the egg at the time of fertilisation determine the telomere length in the offspring.
Their paper in Nature Communications, reveals that optimal mitochondrial function—the powerhouse of the cell—is essential for the natural process of telomere elongation during early embryonic development.
The team conducted the trials using mouse models and found that when mitochondrial activity is disrupted, whether by high oxygen levels, or conditions such as maternal obesity and metabolic syndrome, the embryo fails to properly “reset” its telomere length. This leads to babies being born with shorter telomeres.
“Our findings show maternal health and environmental conditions at the time of conception can have long-term consequences and can even influence the offspring’s susceptibility versus resilience to ageing-associated diseases in later life,” says study co-lead Dr Yasmyn Winstanley.
“These findings highlight that the health of the women and girls should be a major focus of public health policies.”
The research team also examined the capacity to reverse any defects in telomere length through mice that are obese.
“We provide proof-of-concept that DNA resetting can be modulated in embryos where it is deficient, using currently available drugs, to influence telomere length at birth, which is a major marker of lifetime ageing,” says Robker.
“Our identification of specific pharmaceutical compounds that can modulate telomeres during preconception and immediately following fertilisation means that there are therapeutic opportunities to optimise this biology, which is a key determinant of chronic disease risk.”
The researchers are now working with Vitaleon Pharma to develop these new findings into therapies for reproductive medicine and use by fertility specialists.
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