Meioisis is the specialized form of cell division that occurs only in cells destined for sexual reproduction- eggs and sperm.
Cells created through meiosis only have one copy of each chromosome, instead of the usual two in other cells. One of the most commonly observed consequences of reproductive aging is the increased incidence of chromosomal abnormalities that result from improper meiosis with age. The best known example is Down syndrome, a type of chromosomal abnormality known as an aneuploidy, where someone is born with an extra copy of chromosome 21. The reasons for the age-related increase in chromosomal abnormalities are still not fully understood, but scientists know of many biological factors that deteriorate with age that likely cumulatively contribute to this phenomenon. Our grantees are investigating a few of these angles.
GCRLE Grantee projects
Dr Iain Cheeseman: During the process of meiosis, a molecular complex called the centromere guides the collection and assortment of chromosomes into their respective daughter cells. Dr Cheeseman is an expert in centromere function in a variety of contexts- in this project his lab aims to understand how the centromere loses its correct function with age.
Dr Gul Kaya Soygur: A child is born with all the eggs they will ever have- none more are created after birth. Eggs must remain in a poised, frozen state at the beginning stages of meiosis for decades before they undergo the rest of the process when they are ready to mature. It is unclear whether chromosomal abnormalities with older eggs are due to accumulated damages over time, or whether the most healthy, viable eggs are simply selected earlier in life. Dr Soygur is tracing the fate of individual eggs throughout lifespan to determine whether eggs that enter meiosis later have compromised function.
Dr Cristina Candela Quesada: The assortment of chromosomes during meiosis takes many different proteins operating in precise coordination to accomplish. If one of these component proteins is dysfunctional or damaged, aneuploidies or other chromosomal abnormalities may result. Dr Quesada Candela studies the proteasome- a part of the cell that degrades old or damaged proteins, and which loses function with age. An impaired proteasome may lead to faults in the cellular machinery responsible for meiosis. Drugs that improve proteasome function are a promising new frontier in therapeutics for many diseases: Dr Quesada Candela is testing whether they could alleviate the effects of reproductive aging as well.
Dr Ivana Celic: Genomic errors can arise in other ways than chromosomal abnormalities, such as through DNA damage or deterioration, especially in long-lived cells like eggs. One major source of this are LINE1 (L1) retrotransposons, mobile stretches of DNA that can extract and reinsert themselves in different genome locations, where they can interrupt normal functions. Though they comprise 17% of the human genome, healthy cells strongly repress the activity of L1 DNA regions. However, there is evidence that L1 activity is elevated in aged tissues and that this may over time contribute to tissue aging. The Celic lab is using a novel tool they have developed to assess fertility and ovarian aging in mice that have high levels of L1 activity.