Alexander, Courtney et al. (2021) International Worm Meeting "Pseudognaphalium obtusifolium Extract Improves Lifespan and Thermotolerance in C. elegans"

Mosely, Dontae, Deberry, Kazhmiri, Edwards, Ashley, Mariani, Hannah, Alexander, Courtney, Sandefur, Conner

[International Worm Meeting, 2021]

For centuries, Lumbee Indians of North Carolina have used indigenous plants like Pseudognaphalium obtusifolium, rabbit tobacco, to make medicinal teas. Other tribes, like Cherokees and Creeks, used rabbit tobacco teas to combat a host of illnesses and maladies from muscle pain to colds. These teas were believed to have anti-inflammatory properties, though the biology has not been explored. We harvested and dried local rabbit tobacco and prepared aqueous extracts. The extract improved the lifespan, thermotolerance and motility of young adult nematodes, compared to vehicle control. Animals were age-synchronized and exposed to either the aqueous extract or control media. Then, worms were tested for thermotolerance or motility. A lifespan analysis was run in parallel. Nematodes that were treated with rabbit tobacco extract lived longer and had improved thermotolerance and motility. Work is ongoing to determine the molecular mechanism for this phenotype, as well as testing other Lumbee plants. This work helps pave the way for a biological basis for indigenous medicine.

Khare S et al. (2010) Aging, Metabolism, Stress, Pathogenesis, and Small RNAs, Madison, WI "Interaction of a Protein Repair System with Insulin Signaling to Extend Lifespan in Caenorhabditis elegans"

Khare S, Clarke S G, Linster C L

[Aging, Metabolism, Stress, Pathogenesis, and Small RNAs, Madison, WI, 2010]

The protein L-isoaspartyl-O-methyltransferase (PCM-1) functions to repair isomerized aspartyl and asparaginyl residues that spontaneously accumulate with age in a variety of organisms, including Drosophila, C. elegans, and mice. Under standard conditions, pcm-1 deletion mutant C. elegans display a normal lifespan and phenotype (Kagan et al., 1997; Banfield et al., 2008). However, a reduction in lifespan is observed in this mutant in the dauer stage. Moreover, significant defects in development, adult egg-laying, dauer formation, autophagy, and survival have been observed in pcm-1 mutant nematodes under stress conditions (Banfield et al., 2008; Gomez et al., 2008; Khare et al., 2009).An additional mutation in the insulin-like receptor protein DAF-2 prevents the oxidative stress-dependent egg-laying defect and the dauer formation defect observed in pcm-1 mutant nematodes, indicating that PCM-1 may either be working upstream or in parallel to the insulin signaling pathway to promote resistance to stress and regulate dauer formation (Khare et al., 2009). These exciting results have led us to further investigate the relationship between PCM-1 and the insulin signaling pathway in the context of aging. Interestingly, overexpression of this repair enzyme in both Drosophila and C. elegans extends adult lifespan (O' Conner et al., 1988; Banfield et al., 2008). Our preliminary results have led us to hypothesize that PCM-1 may be acting either directly or indirectly on the DAF-16 transcription factor to inhibit insulin signaling and extend lifespan. We have found that reducing DAF-16 levels by RNA interference (RNAi) reduces the lifespan extension displayed by the PCM-1 overexpressor strain. Our results from quantitative real-time PCR (qPCR) analysis reveal an up-regulation of daf-16-dependent stress response genes in the PCM-1 overexpressor animals compared to wild-type and pcm-1mutant nematodes under normal and acute thermal stress conditions. Additionally, similar to other long-lived C.elegans mutant strains, including daf-2and age-1 mutants, PCM-1 overexpressor adult animals display increased resistance to severe thermal stress. Our results support a role for protein repair in lifespan extension dependent on the insulin signaling pathway.