The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model.
On the other hand, since Nox4 consumes NADH as an electron donor to produce O2−, downregulation of Nox4 could lead to accumulation of NADH, a condition opposite from that induced by caloric restriction, an established intervention attenuating aging.
In addition to such attenuated aging phenotypes, the NMR is also unusual for its pronounced cancer resistance (Liang et al., 2010), which, in part, has been explained by high molecular mass hyaluronan (Tian et al., 2013).
Selective 11β-HSD1 inhibitorshownown to attenuate age-related memory impairments in aged mice (Sooy et al., 2010; Yau et al., 2015), could be beneficial in the treatment of stress-related cognitive disorders.
Caloric restriction (CR) and antioxidants have been proposed as strategies to attenuate age-related brain changes.
Since the p16INK4A expression was reported as a robust in vivo biomarker in human and rodent with advancing age [21], [24], the suppression of p16INK4A by SIRT1 may benefit to attenuate age-related diseases.
These findings would allow the use of powerful molecular biological resources accumulated in the zebrafish field to address the mechanisms of cognitive senescence, and promote the search for therapeutic strategies which may attenuate age-related cognitive decline.
