Research Paper Volume 10, Issue 12 pp 3910—3937
SIN-3 as a key determinant of lifespan and its sex dependent differential role on healthspan in Caenorhabditis elegans
- 1 Dr. B. R. Ambedkar Centre for Biomedical Research, University of Delhi, Delhi -07, India
received: July 7, 2018 ; accepted: November 22, 2018 ; published: December 12, 2018 ;https://doi.org/10.18632/aging.101682
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Copyright: Pandey et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Aging/senescence includes not just decline in lifespan but also etiologies of age associated morbidities which are inadequately understood. Extensive research has been undertaken to delineate the pathways and generate mutants with extended lifespan. However, little is known about the health status of these long lived mutants in the background of important genetic perturbations. Caenorhabditis elegans is one of the leading in vivo model organisms to study aging. Deletion of SIN-3, a transcription coregulator in C. elegans has been shown to reduce the lifespan of the mutant worms by half as compared to the wild-type and isogenic controls. The current study focuses on the effect of SIN-3 deletion on the healthspan of the worms. We find that not only are sin-3 mutants more susceptible to stress, but the overall stress intolerance and physiological decline is sex dependent. The severity of the phenotype is more pronounced in hermaphrodites as compared to the males carrying the same mutation with respect to the controls. The results further suggest that genetic perturbation along with the gender play an important role in determining the lifespan, healthspan and overall fitness of an organism.
ATP: adenosine triphosphate; Sin-3: Swi-independent-3; NGM: nematode growth medium; HDAC: histone deacetylase; HID: HDAC interacting domain; PAH: paired amphipathic α-helix; HCR: highly conserved region; ROS: reactive oxygen species; AVID: age associated vulval integrity defect; DNPH: 2,4-dinitrophenylhydrazine; JC-1: 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetra-ethyl benzimidazolylcarbocyanine iodide; PBS: phosphate buffered saline; DMSO: dimethyl sulfoxide.