Ovarian ageing studied using molecular atlas

Genetic and molecular changes occurring during ovarian ageing have been mapped to single-cell resolution.

Using four ovaries from young women (23-29 years old) and four from reproductively-aged women (49-54 years old), researchers investigated gene expression and chromosome structure changes during ovarian ageing. The team, led by Dr Yousin Suh, at Columbia University Department of Genetics and Development, New York, has identified a coordinated pattern of changes in gene expression as ovaries age.

'We just don't consider women in their 30s to 50s in that 'old' category,' Dr Suh told Business Insider. 'But I think that tide has turned because we know this is an ageing process and it has significant clinical and societal implications. So more and more people are paying attention to this concept of ovarian aging and considering it as a true ageing process.'

The study, published in Nature Ageing, identified 3455 genes whose expression was increased or decreased with age. Up-regulated genes included those related to cell senescence (the process of coordinated cell death), and insulin and mTOR signalling pathways, both thought to be central to cellular ageing. Meanwhile, DNA-repair associated genes were down-regulated. Crucially, the researchers found that these ageing-related changes occur faster and in a much more coordinated way in ovaries compared with other tissues in the body.

The work forms part of the Human Cell Atlas, an international consortium aimed at creating a molecular atlas of all cells in the human body. Single-cell and single-nucleus sequencing technologies enable high-resolution mapping of gene expression in many thousands or millions of individual cells. Collectively, these and other techniques are known as 'single-cell multi-omics' and are used to determine the precise molecular changes which define cell types and their development. Spatial transcriptomics has previously elucidated gene-expression patterns defining human follicle development and ovule formation (see BioNews 1234).

Previous studies have revealed genes influencing age at natural menopause, a marker for reproductive ageing among women, using large scale genetic studies known as genome-wide association studies. But until now, scientists haven't been able to implicate how these genes act in concert to contribute to ovarian ageing at the molecular level.

Professor Francesca Duncan of the Feinberg School of Medicine, Northwestern University, Illinois, who was not involved in the study, told Business Insider: 'This is the first time where you've seen a really solid study done by a leading ageing researcher that is demonstrating that a very highly conserved pathway that drives ageing is happening in the ovary'.

The team hope their findings will enable treatments to slow the ageing of ovaries and enhance fertility outcomes for patients. Dr Suh is also involved in a study investigating the effects of the drug rapamycin on ovarian ageing rate in perimenopausal women.