6/25/24

How Pregnancy Affects Aging, New Model Organisms for Aging Research, HRT | 43 - Berenice Benayoun

Matt recently attended the 52nd annual meeting of the American Aging Association (AGE) in Madison, Wisconsin and met with several people doing fascinating work in the longevity field.

One of these was Berenice Benayoun, an Associate Professor (recently tenured!) of Gerontology, Biological Sciences, Biochemistry, and Molecular Medicine at the University of Southern California Leonard Davis School of Gerontology. Berenice delivered the keynote speech at the 2024 AGE meeting, where she received the 2024 Vincent Cristofalo Rising Star Award in Aging Research. Her research focuses on the influence of genomic regulation mechanisms, environmental stimuli, and factors such as biological sex on vertebrate aging and healthspan. Berenice was named a 2020 Pew Biomedical Scholar and a 2021 Nathan Shock new Investigator, and also received the 2019 Rosalind Franklin Young Investigator Award in Mammalian Genetics, an American Federation of Aging Research Junior Faculty Award, and a Global Consortium for Reproductive Longevity and Equality GCRLE Junior Scholar Award.

In this episode, Matt and Berenice chat about the ovaries as a vehicle for understanding aging, the difference between estropause and menopause, and the controversies associated with hormone replacement therapy, and how Berenice made her way into the lab of her dreams. They also discuss the African turquoise killifish, a new vertebrate model organism for longevity research, and address a couple of questions about research we have recently featured on this podcast (how pregnancy affects aging, and sex-specific differences in the effects of estradiol on mouse aging).

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

The Benayoun Lab

The Benayoun lab at the University of Southern California Leonard Davis School of Gerontology is looking for postdoctoral fellows, PhD students, undergraduate researchers interested in uncovering the molecular regulation of vertebrate aging. If you might be one of them, or simply want to learn more about what Berenice and her colleagues do, check out this page to find papers that have come out of the Benayoun lab, the lab's funding sources and affiliations, courses that Berenice is teaching, and more.

Microglia undergo sex-dimorphic transcriptional and metabolic rewiring during aging

This paper, which Berenice coauthored with colleagues, demonstrates that aging of the microglia—a type of immune cell located in the brain—occurs differently in male and female mice. More aging-associated changes happen in the microglia of female than in those of male mice, and these differences are particularly evident in old microglia compared to young microglia. The study outlines potential mechanisms that underpin these microglial changes.

Protection against APOE4-associated aging phenotypes with the longevity-promoting intervention 17α-estradiol in male mice

In this preprint, Berenice and colleagues examined the effect of 17α-estradiol, a type of estrogen, on outcomes in male mice with an age-accelerating allele called apolipoprotein E4 (APOE4). This allele is a major genetic risk factor for Alzheimer's disease and age-related cognitive impairment. The researchers found that 17α-estradiol administration to APOE4 mice conferred healthspan benefits across various systems. You may recall our discussion of the Interventions Testing Program’s finding that 17α-estradiol extends lifespan in male mice.

Estropausal gut microbiota transplant improves ovarian function in adult mice

Transplanting things—blood, ovaries, poop—can have surprising beneficial effects on aging. This preprint, which Berenice coauthored, found that mice receiving gut microbiota transplants experienced better fertility and ovarian health. They also identified clear differences between the gut microbiota of young and old mice as well as specific gut microbes that may be responsible for the improvements observed with transplants.

Menopause Is More Than Just Loss of Fertility

Berenice and Benayoun lab PhD Clayton Baker co-wrote this article reviewing the surprising negative effects of menopause on cognitive function, bone mass, and cardiovascular disease risk. They make the case for paying attention to biological differences between men and women and the resulting differences in drug pharmacokinetics in both genders, and for addressing limitations in women's health such as a lack of female representation across the age spectrum in interventional clinical trials.

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