Matt recently attended the 52nd annual meeting of the American Aging Association in Madison, Wisconsin and met with several people doing fascinating work in or adjacent to the geroscience field.

One of these was Cristal Hill. Cristal is an Assistant Professor of Gerontology at the University of Southern California Leonard Davis School of Gerontology, where she runs a lab focused on how dietary protein might affect adipose tissue (body fat) function, metabolic, and endocrine health during aging. Cristal received postdoctoral training at the Pennington Biomedical Research Center of Louisiana State University, a PhD in molecular biology from Southern Illinois University, and a B.S. in Animal Sciences from Tuskegee University.

In this episode, Matt and Cristal discuss fibroblast growth factor 21 (FGF21), a hormone produced mainly in the liver that helps regulate metabolism and control how the body uses sugar and fat for energy. They also chat about FGF21's influence on food preferences, role in healthy aging and longevity, potential as an obesity treatment, and more, as well as the broader impact of protein restriction on health- and lifespan as we age.

Some definitions: the term "wildtype" refers to the typical form of an organism or gene as it occurs in nature, and represents the standard or normal genetic makeup and phenotype against which mutants or genetically modified organisms are compared. A "knockout" is an organism in which a specific gene has been completely disabled or "knocked out" to study the gene's function by observing the differences between the knockout organism and a wildtype one. Finally, a "transgenic" organism is one that has had a gene or genes introduced into its DNA to give the organism new traits or abilities, such as resistance to diseases, or to study the effects of the introduced gene.

As far as we can tell, FGF21 tests are not yet commercially available.

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 Hill lab

If you're an aspiring undergraduate researcher, PhD or MD student, postdoc, potential collaborator, or even just someone who wants to know more about what Cristal and her team get up to, here's where you can go to learn all about Cristal's lab at the University of Southern California. On this page you'll find a comprehensive list of the Hill lab publications, some of which deal with the topics that Cristal and Matt discuss in this podcast. You can also read a summary of the Hill lab's research interests.

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

This paper presents data showing a fairly impressive lifespan extension of ~30% and ~40% in male and female mice respectively after overexpression of fibroblast growth factor-21, or FGF21. Caloric restriction brings about a similar lifespan extension. The authors suggest that the mechanism behind this effect could involve the growth hormone/insulin-like growth factor-1 signaling axis. FGF21 administration may produce some adverse effects, such as reduced bone mass.

FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice

Cristal and Matt discuss this research in the podcast episode. Cristal is the lead author on this paper demonstrating the effects on protein restriction on male mice, which include lower frailty, functional decline, body weight, and adiposity; improved physical performance and glucose tolerance; altered biomarkers in the liver, adipose tissue, and blood; and longer lifespan. The paper demonstrates the essential role of FGF21 in bringing about the lifespan extension effect of protein restriction in mice: mice without FGF21 do not respond favorably to protein restriction.

FGF21 prevents low-protein diet-induced renal inflammation in aged mice

In this paper, Cristal and colleagues demonstrate how a low-protein diet impacts aging kidneys as well as the degree to which FGF21 mediates those effects. Mice lacking FGF21 had greater kidney damage and inflammation as a result of protein restriction than mice with FGF21, suggesting that FGF21 may help prevent kidney pathology. Interestingly, protein restriction does not seem to have adverse effects on aging kidneys in humans.

FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism

This study, also from the Hill lab, presents data about the role of FGF21 in energy metabolism and nutrient preferences, or feeding behavior, in mice undergoing protein restriction. FGF21 is responsible for changes in protein appetite, growth, glucose intolerance, and more in response to a low-protein diet.