University of Arizona Assistant Professor of Molecular and Cellular Biology George Sutphin runs a lab that investigates genetic determinants of longevity, the effects of kynurenine-based interventions on lifespan, and environmental regulators of the aging process. George, who was an aerospace engineer before he discovered the promise of geroscience, completed his PhD at the University of Washington and worked as a postdoctoral associate at the Jackson Laboratory prior to his current faculty position. He currently serves as Chairperson of the American Aging Association.

We sat down with George to talk about his research, including the effects of caffeine on lifespan and, more recently, his discovery of a new metabolite with the ability to greatly extend lifespan when given late in life. We also discuss George's thoughts on biological age clocks, his own healthspan optimization protocol, and much more.

The probiotic George mentions taking in this podcast episode is Garden of Life Probiotics Ultimate Care.

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!

Caffeine extends life span, improves healthspan, and delays age-associated pathology in Caenorhabditis elegans

This paper began as a side project during George’s PhD work at the University of Washington. It showed that caffeine extended life- and healthspan in nematode worms, and also had positive effects on pathologies such as paralysis in a worm model of polyglutamine disease. The paper attracted a lot of interest, perhaps because it seemed to justify people’s coffee-drinking habits. No conclusive evidence about caffeine’s effects on human lifespan currently exists.

Lifespan extension in Caenorhabditis elegans by complete removal of food

What is the optimal amount of food to give worms so that they’ll live longer? According to this study, which also came out of George’s PhD at the University of Washington, the answer is no food at all. This paper found that completely taking away worms’ food in adulthood increased lifespan by up to 50%. While a starvation protocol like this one is unlikely to work in humans, these findings add an interesting set of data points to evolving research into how diet affects longevity in humans.

Dietary restriction by bacterial deprivation increases life span in wild-derived nematodes

This study was a follow up to the previous paper and investigates the effects of dietary restriction on the lifespan of wild worm populations collected from various locations worldwide. The results indicate that bacterial food deprivation extends lifespan across multiple wild C. elegans (a worm species) populations. Additionally, the longevity-enhancing effects of bacterial food deprivation are conserved in a related worm species, C. remanei. The study highlights the potential impact of genetic and environmental factors on worm lifespan variation and suggests that food-deprivation-induced lifespan extension may be a characteristic of wild-derived nematode populations.

Caenorhabditis elegans orthologs of human genes differentially expressed with age are enriched for determinants of longevity

This paper came out of George’s time at the Jackson Laboratory. The researchers conducted an RNA interference (RNAi) longevity screen on 82 genes in C. Elegans, chosen based on their orthology to human genes that show age-related changes in expression. Their results revealed a significant enrichment in genes where knockdown increased lifespan compared to previously published longevity screens, with 46 genes being newly identified as impacting lifespan. Knockdown of these genes, which included genes that encoded the enzyme kynureninase, a tetraspanin, and a voltage-gated calcium channel subunit, increased healthspan with no effects on reproduction. The kynureninase gene knockdown specifically delayed pathology in worm models of Alzheimer's and Huntington's diseases.

The Emerging Role of 3-Hydroxyanthranilic Acid on C. elegans Aging Immune Function

3-hydroxyanthranilic acid (3-HAA) is a metabolite within the kynurenine pathway, a metabolic pathway involved in the breakdown of the amino acid tryptophan. The kynurenine pathway plays a crucial role in various physiological processes, including immune response regulation, neurotransmitter synthesis, and inflammation modulation. This paper showed that the 3HAA appeared to slow age-associated immune function decline in addition to helping mice fend off pathogenic challenges. 3HAA is not sufficiently well-understood to be a candidate for supplementation in humans.