Tig-2 Modulates Age-related Mobility Loss And Lifespan In C. Elegans
Aging, as a time-dependent physiological functional decline, is driven by multiple factors, and is accompanied by an increased risk of many chronic diseases, such as cardiovascular disorders, diabetes, cancer, and some neurodegeneration diseases. Among all age-related functional decline, locomotion impairment is one of the most prominent outcomes. Although slower movement with age could result from multi types of impairment in different tissues, previous research highlights the age-dependent changes at neuromuscular junctions (NMJs) play a key role in mobility loss. Given its short lifespan and tractable genetic tools, nematode C. elegans offers an ideal model for aging study, especially at genetic and cellular levels. Previous study has demonstrated that age-related decline in neurotransmission at NMJs directly induces slow locomotion in older C. elegans. However, the underlying biological principals of age-related functional deterioration at NMJs is still unclear. Here, we show that a genetic mutation in tig-2, a retrograde BMP signaling of TGF-β family not only slows age-related mobility loss, but also extends lifespan in C. elegans. Surprisingly, tig-2 mutant exhibit comparable presynaptic components and physiological function of body wall muscle cells as wild type worms, suggesting an unknown physiological function of TIG-2 in C. elegans. We also found the functional decay in NMJs by exposing worms to aldicarb and electrophysiology recording. In addition, the copy of mitochondria DNA is reduced in tig-2 mutant, which indicated the decreased number of mitochondria. The lower ATP level of tig-2 mutant compared with that of wide type worms is also consist with the mobility loss in the early life of C. elegans.