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

One of these was Mark McCormick, an Assistant Professor at the University of New Mexico (UNM) Department of Biochemistry and Molecular Biology. At UNM, Mark runs a lab that investigates age-delaying drug targets, develops machine learning tools for studying aging, and identifies conserved aging mechanisms and pathways in model organisms and humans. Mark previously completed a postdoc with Brian Kennedy at the Buck Institute for Research on Aging, a PhD in Biochemistry and Molecular Biology with Cynthia Kenyon at the University of California, San Francisco, and a B.S. in Mechanical Engineering as well as a B.S. in Biology from the University of Texas at Austin.

In this episode, Matt and Mark chat about aminoacyl-tRNA synthetases, a group of enzymes that play an essential role in protein synthesis. They discuss the promise and risks of tRNA synthetase inhibitors to treat diseases of aging and extend life- and healthspan (spoiler: don't take tRNA synthetase inhibitors yet). They also talk about why Mark's lab has held off on doing mouse experiments thus far, the challenges of proving causality in longevity experiments, interventions about which Mark is optimistic (or not), and more.

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!

McCormick lab

If you're an aspiring undergraduate researcher, PhD student, postdoc, collaborator, research sponsor, or even just someone who wants to know more about what Mark and his team get up to, here's where you can go to learn all about Mark's lab at the University of New Mexico. Many who know Mark can attest to the care and effort he puts into mentoring the next generation of scientists. On this page, you will also find a comprehensive list of Mark's lab publications from which you can learn more about some of the topics he discusses in this podcast (and more).

Induction of proteasomal activity in mammalian cells by lifespan-extending tRNA synthetase inhibitors

Mark coauthored this paper discussing a potential mechanism of action of tRNA synthetase inhibitors to increase lifespan. The researchers demonstrate that tRNA inhibitors may upregulate pathways that promote protein turnover, specifically proteasomal degradation and autophagy, a process of breaking down damaged proteins and other cellular components. Protein turnover is essential for maintaining cellular function and homeostasis, and disruptions in protein turnover can contribute to various diseases via the accumulation of damaged or misfolded proteins or the excessive degradation of functional proteins.

Cytosolic and mitochondrial tRNA synthetase inhibitors increase lifespan in a GCN4/atf-4-dependent manner

This paper, which Mark also coauthored, demonstrates lifespan extensions in both yeast and worms as a result of tRNA synthetase inhibitors. The study hypothesizes that these inhibitors act in yeast by upregulating the translation of General Control Nonderepressible 4 (Gcn4), a crucial yeast transcription factor that regulates the expression of genes required for amino acid biosynthesis and stress adaptation. Meanwhile, tRNA synthetase inhibitors act in worms in an Activating Transcription Factor 4 (ATF4)-dependent manner. ATF4 is a mammalian transcription factor that plays a key role in the cellular response to various forms of stress.

Roles of tRNA metabolism in aging and lifespan

This review provides an overview of how tRNA metabolism, including tRNA transcription, tRNA molecules, tRNA modifications, tRNA aminoacylation (where tRNA-synthetase comes in), and tRNA derivatives, influences aging and lifespan.

Acarbose improves health and lifespan in aging HET3 mice

Matt and Mark discuss the merits of acarbose, an antidiabetic drug that slows carbohydrate digestion and absorption, as a potential longevity intervention in this podcast episode. This study is one of several reporting lifespan increases in mice receiving acarbose, with some sex differences. The field doesn't yet have a lot of data about the effects of acarbose on human longevity.