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Caveolin‐2: Improves Longevity and Allows for Stress Adaptation in C. Elegans
Author(s) -
Mehta Meghna D.,
Schilling Jan M.,
Mehta Ekta D.,
Fridolfsson Heidi N.,
Roth David M.,
Patel Hemal H.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.990.4
Subject(s) - caenorhabditis elegans , biology , gene isoform , microbiology and biotechnology , longevity , model organism , gene knockdown , gene , adaptation (eye) , caveolin , signal transduction , genetics , caveolae , neuroscience
Caveolins are scaffolding proteins that are involved in stress adaptation via regulation of signal transduction and endocytosis. Three isoforms of caveolin (Cav‐1, Cav‐2, and Cav‐3) are expressed in mammalian cells, while C. elegans express only two (Cav‐1 and Cav‐2). Cav‐2 has conserved homology to the mammalian isoforms Cav‐1 and Cav‐3, with the amino acid region being 67% similar and 37% identical. As aging and diabetic studies are lengthy in mice, a model species such as C. elegans could qualify for high throughput evaluation of the role of caveolin in stress and adaptation since their lifespan is generally under 30 days. Benefits of C. elegans as a model organism are that their whole genome has been sequenced and that they are the only organism to have a complete connectome. Hypothesis We hypothesized that expression level of Cav‐2 in C. elegans is a major regulator of stress adaptation with increased expression leading to better, and decreased expression leading to worse stress response. Methods We generated C. elegans overexpressing Cav‐2 (Cav‐2 OE) gene through microinjection and transformation with a global promotor. The worms were grown on 1.7% agar plates containing E. coli OP50. We assessed the impact of the Cav‐2 gene on longevity, egg laying, and stress adaptation by comparing the N2 control with the Cav‐2 OE and Cav‐2 KO. Results Cav‐2 OE worms showed a 13.3% increase in median lifespan compared to N2 controls and Cav‐2 KO worms (p<0.001, n=180, Log‐Rank Test) under normal conditions. Cav‐2 OE worms had a 28% and 41% increase in production of eggs compared to the N2 controls and Cav‐2 KO worms, respectively. Cav‐2 OE worms also had an 18% increase in the duration of egg laying compared to both N2 controls and Cav‐2 KO worms (p<0.0001, n=180, 2‐Way RM ANOVA). In order to examine the ability of C. elegans to adapt to stress, we induced stress by exposing the C. elegans to 2% glucose. Cav‐2 OE worms showed a 8% and 27% increase in lifespan compared to N2 controls and Cav‐2 KO worms, respectively (p<0.0001, n=180, Log‐Rank Test). Conclusion Taken together, our data suggests that Cav‐2 is a major regulator of longevity and stress adaptation in C. elegans and C. elegans may serve as an ideal model system to evaluate the impact of caveolin on human physiology and aging. Support or Funding Information This research was supported by funds from the UCSD Department of Anesthesiology.