Why do females age differently than males? New study to investigate

A new research project led by USC Leonard Davis School of Gerontology Assistant Professor B?r?nice Benayoun aims to learn more about why female mammals, including humans, age differently than males.

Sex dimorphism – physiological characteristics that differ between the sexes in a species – can have big implications for health and lifespan. Human longevity differs markedly between sexes, with women consistently having a higher average lifespan than men, and this pattern has also been observed throughout many other mammals. In addition, other health indicators such as immune response and even the regulation of gene expression also differ based on sex hormones and chromosomes, Benayoun said.

“Despite the potential significance of sex-dimorphic mechanisms, remarkably little is known about differential genomic and functional regulation in female vs. male aging,” Benayoun wrote in her proposal for the Pew Scholars Program in the Biomedical Sciences, a grant program of the Pew Charitable Trusts. She is one of 22 early-career scientists named to the program this year in the United States.

Early-career scientist receives opportunity to study male and female aging

The Pew Scholars Program provides four years of funding for “foundational research to pursue scientific breakthroughs and advance human health,” according to a June 15, 2020 press release announcing the new scholars.

“Pew is proud to support these promising researchers as they conduct world-class research to address biomedicine’s most complex questions,” said Rebecca W. Rimel, Pew’s president and CEO, in the release. “They join a group of distinguished scientists who have worked for decades to advance science and protect public health.”

Benayoun plans to study a unique animal model called the Foxl2 inducible knockout mouse, in which shutting off the Foxl2 gene in adult female mice turns on genes that convert ovary tissues into testes, resulting in the genetically female mice producing as much testosterone as their genetically male littermates. This process allows researchers to observe the effects of both female and male hormone profiles in otherwise genetically identical mice, separating the influence of sex hormones from the influence of sex chromosomes.

Benayoun especially looks forward to studying how the Foxl2 knockout mice age and respond to immune system challenges, which has never been done before. In particular, her project will examine the links between chromosomal sex, hormone profiles, and the function of immune cells called macrophages, which play major roles in inflammation and damage repair in the body.

“This is really an unprecedented model to understand the biology of health disparities between females and males and start addressing health in a more personalized fashion,” Benayoun said.

Benayoun expressed her gratitude for the opportunity to be a part of the Pew Scholars Program and for the support of an ambitious and unprecedented research project.

“Being part of Pew Scholars program is amazing for many reasons. A main reason is a recognition of my past work and of my promise as an independent scientist – a rare and prestigious accolade from the scientific field, and the opportunity to try my ‘crazy’ project, which would be hard to support on traditional National Institutes of Health funds,” she said. “It’s also extremely humbling to join the ranks of such a prestigious network of innovative young principal investigators. It will be an amazing network to be part of, get feedback from, and grow with scientifically.”

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