Depending on how you look at them, aging genes are genes whose expression changes in a predictable with age or genes that influence an organism's lifespan by affecting various biological processes associated with aging. Research on aging genes not only deepens our understanding of the biological aging process, but also opens up potential avenues for developing therapies aimed at extending healthy human lifespan. By targeting these genes, scientists hope to delay the onset of age-related diseases such as Alzheimer's disease, cardiovascular disease, and cancer, ultimately promoting a longer and healthier life.

In this episode, Matt discusses several ways we can identify and categorize aging genes. He talks about how genes can serve as predictive signatures of chronological or biological age, potential conserved genetic regulators of longevity, and how unbiased genetic screens can still be biased. He also provides his unique perspective on aging genes in humans and the potential to optimize longevity through genetic modulation.

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!

A C. elegans mutant that lives twice as long as wild type

Matt calls the daf-2 gene "the classic aging gene". This paper, authored by Cynthia Kenyon in 1993, demonstrated that a single genetic mutation in the daf-2 gene more than doubled the lifespan of C. elegans, a common model organism for geroscience research. This daf-2-mediated lifespan extension requires the activity of a second gene, daf-16.

The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms

This paper, which Matt coauthored with 2 colleagues using work from his PhD thesis, demonstrates that inserting a second copy of the sir2 gene increases lifespan in yeast.

Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production

Matt discusses growth hormone mutants as potential lifespan regulators in this podcast. This paper suggests that mice with genetic mutations in the growth hormone pathway have a lifespan increase of over 40 percent as well as delays in several other biological markers that change with age.

Evidence that conserved essential genes are enriched for pro-longevity factors

In this pilot study, Matt and colleagues overexpressed several essential yeast genes one by one and found that 21 percent of genes increased yeast replicative lifespan. By comparison, only around 3.5 percent of genes have an impact on lifespan when deleted. This is one of the few studies that has examined the impact of turning up essential genes on lifespan.

APOE2 is associated with longevity independent of Alzheimer’s disease

This study presents evidence for an association between the ε2 allele of apolipoprotein E (ApoE), a protein that plays significant roles in lipid metabolism and neurological functions, and longevity. This association holds irrespective of Alzheimer's disease status (researchers have linked variations in ApoE to Alzheimer's disease and other neurological conditions).