Enhancement of longevity and metabolism
The knockout of RGS14 (Regulator for G Protein Signaling 14) extends the lifespan of mice and has many beneficial effects on healthy aging. These include protection against obesity as shown by decreased white adipose tissues, protection from cold exposure and improved metabolism. The beneficial effects observed were mediated through improved mitochondrial functions. The main mechanism for the RGS14 knockout mice’s beneficial properties was an increase in brown fat tissue. This was confirmed through surgically removing the BAT and transplanting it into wild-type (WT), a surgical simulation to a molecular mutation. This technique reversed phenotypes of RGS14KO and WT mice, leading to loss of improved metabolism and protection from cold exposure for RGS14KO and conferring protection to WT BAT recipients. Increased SIRT3 was another mechanism that mediated the beneficial features of the RGS14KO. The RGS14 X SiRT3 double-KO confirmed this mechanism, as it no longer showed improved metabolism or protection against exposure to cold. The evolutionary conservation of the mechanism was confirmed by the loss of function in the Caenorhabditis-elegans RGS-14 ortholog. RGS14 disruption is therefore a model for healthy aging. It not only increases lifespan but also protects from obesity, cold exposure, and improves metabolism.