New ways to extend mouse life span arrive at a steady pace these days. It's all largely genetic engineering to alter the operation of metabolism in various ways, and the results help to shed light on the roles of specific genes and on the way in which metabolism and environment together determine the pace of aging. These examples of life extension are not rejuvenation, however, and nor do they lie on any road that leads to rejuvenation. Thus they have little to no bearing on whether or not you and I will lead extended healthy lives: the only way that will happen is for research programs like SENS to make significant progress. SENS-like research aims to repair the underlying causes of aging in a deliberate, targeted fashion and thus reverse aging. It is a completely different approach to research and the development of therapies than that of trying genetic alternations in search of those that can modestly slow down aging.
But still, I post on the topic of genetically engineered mouse longevity for the same reasons I post on topics like the evolution of aging - because it is interesting, not because it will necessarily have any meaningful application in the near term. Below is a recent example in which the human gene for MTH1 / NUDT1 causes enhanced longevity when expressed in mice. The enzyme produced from this genetic blueprint cuts down on oxidative damage to both nuclear and mitochondrial DNA, and the gain in mouse life span is thus an expected outcome under any of the free radical theories of aging.
In this study we used the hMTH1-Tg mouse model to investigate how oxidative damage to nucleic acids affects aging. hMTH1-Tg mice express high levels of the hMTH1 hydrolase that degrades 8-oxodGTP and 8-oxoGTP and excludes 8-oxoguanine from both DNA and RNA. Compared to wild-type animals, hMTH1-overexpressing mice have significantly lower steady-state levels of 8-oxoguanine in both nuclear and mitochondrial DNA of several organs, including the brain. hMTH1 overexpression prevents the age-dependent accumulation of DNA 8-oxoguanine that occurs in wild-type mice.
These lower levels of oxidized guanines are associated with increased longevity and hMTH1-Tg animals live significantly longer than their wild-type littermates. Neither lipid oxidation nor overall antioxidant status are significantly affected by hMTH1 overexpression. The significantly lower levels of oxidized DNA/RNA in transgenic animals are associated with behavioral changes. These mice show reduced anxiety and enhanced investigation of environmental and social cues.
There some muddying of the water here, of course. Nothing is ever simple in biology. The first item to consider is that it's possible that differences in activity levels in the mice could account for some of the longevity differences shown in the research. This is hard to control for, harder than calorie restriction, which is the other thing you have to keep track of in any mouse study. If your mice happen to eat less because your treatment makes them nauseous, or they eat less because they're spending more time running around, then they'll live somewhat longer.
The more interesting line item, however, is the difference between reducing oxidative damage to nuclear DNA versus reducing oxidative damage to mitochondrial DNA. There is some debate over whether nuclear DNA damage contributes meaningfully to aging (as opposed to its contribution to cancer risk), whereas there is a far greater consensus on the importance of mitochondrial DNA damage in degenerative aging. More of it is bad, less of it is good.
I would be very interested to see the results of a similar study in which researchers figure out how to keep the protective enzymes localized to either the nucleus or the mitochondria. My expectation would be that you'd only see increased life span for the mitochondrial localization, which would make sense when considering the extended life that result from studies in which levels of natural antioxidants like catalase are enhanced in mouse mitochondria.