Specific reduction in complex I of the mitochondrial electron transport system in long-lived seed beetles

  • Author / Creator
    Mast, Heather
  • Background: Mitochondrial dysfunction is a recognized hallmark of aging that is also directly or indirectly connected to practically all the other hallmarks of aging. As a result, mitochondrial dysfunction seems to be an important regulator of lifespan. Many studies provide evidence of lifespan extension following a decrease in mitochondrial complexes, but few studies have actually measured and compared integrated mitochondrial function. Additionally, most studies on longevity are on a limited number of animal models, such as Drosophila and Caenorhabditis elegans.
    Methods: Here, we measured integrated mitochondrial function in the seed beetle, Acanthoscelides obtectus. This animal model has been selected for early (E) and late (L) reproduction for nearly four decades and over 250 generations, leading to two lines of the same animal species, each with a very different longevity (7 days in E line, 12-14 days in L line). First, we determined mitochondrial content and used high-resolution respirometry to measure the NADH, Succinate, and Proline dehydrogenase pathways and complex IV in short-lived (E line) and long-lived (L line) beetles of both sexes and at 3 timepoints (days 1, 5, and 8). Second, we determined complex I, complex II, and complex IV’s control over combined NADH+Succinate+Proline flux in male beetles at days 1 and 5. Lastly, we tested fatty acid oxidation.
    Results: The NADH pathway’s contribution to maximal flux was lower and the Succinate pathway’s contribution was higher in L line beetles, mostly at days 1 and 5, suggesting a link between early differences in mitochondrial function and longevity. Control by complex I was also stronger and complex IV had a higher excess capacity in L line beetles at day 1 of age. Male beetles tended to have more longevity-linked differences compared to females. There were no differences in proline and fatty acid metabolisms between the beetle selection lines.
    Conclusion: The combined reduction in the NADH pathway and increased control of mitochondrial respiration by complex I suggest that complex I contributes to the lifespan extension seen in L line beetles. The opposite seems to be true for E line beetles. This work, comparing different selection lines within the same animal species, reinforces the involvement of mitochondrial dysfunction in lifespan while also evaluating sex differences and additional metabolic pathways.

  • Subjects / Keywords
  • Graduation date
    Spring 2023
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.