Of mice and (space)men

It may seem obvious, but when encountering longevity research, it bears repeating: human biology is not mouse biology. For this reason, one of my resolutions for 2017 was to minimise blogs centered around rodents. But longevity science, much like Disney, finds functioning without the mouse more or less unthinkable. Our recent foray into the world of monkeys, was only delaying the inevitable. When it became obvious that mice were turning the wheel, not just for medical progress, but also towards the stars, well, I realised there's always 20181.

DNA damage has been found to accumulate with advancing age. This is unsurprising. Since simple sunlight and other aspects of our environment are considered mutagenic, the longer we interact with that environment the greater our incidence of genetic mutation. For this reason, DNA repair is an innate and very important feature of our cells, but it is an ability that appears to decline with age. That this ability would contribute to human longevity seems sensible, but by precisely how much is uncertain. However, since research suggests that Jeanne Calment's longest recorded human lifespan arose because of her superior genomic stability, it is clearly an important part of the picture.

In March 2017 researchers lead by David Sinclair at Harvard Medical School published a striking paper on DNA repair and aging within mice. They showed the importance of the signaling molecule NAD+ in up-regulating DNA repair, alongside outlining the process by which DNA repair is inhibited as levels of NAD+ decline with age. An earlier paper from Sinclair had shown that the NAD+ precursor NMN could be administered to mice and seemingly reverse aspects of the aging process, such as insulin resistanceinflammation and muscle wasting. The same intervention had now been shown to also mitigate age- or radiation-related DNA damage. Unsurprisingly, human trials will begin this year.

What is already a fascinating story doesn't end there, however, since it isn't just our everyday environment that contains mutagens. Travel outside Earth's magnetosphere involves greater exposure to energetic radioactive particles. This fact, already a direct concern of NASA, is made no less pressing by recent US Government statements on human trips to Mars. Current research suggests that astronauts on such a trip would suffer significant DNA damage and therefore face a higher risk of developing cancer. Interventions to enhance human DNA repair mechanisms are clearly vital for the success of such missions. For this reason the researchers behind this work were NASA iTech finalists, winners in a competition designed to sponsor technologies necessary for future space exploration. So it's not just a case of watch this space, but keep an eye on the one up there too!

1. It could be worse, since mice are at least mammals. We can be grateful this blog wasn't about yeast


Soares, J.P. et al. (2014) Aging and DNA damage in humans: a meta-analysis study. Aging. doi: 10.18632/aging.100667.

Sinclair, D.A. et al. (2017) A conserved NAD+ binding pocket that regulates protein-protein interactions during aging. Science. doi: 10.2105/AJPH.2007.122382.

Sinclair, D.A. et al. (2013) Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication during Aging. doi: http://dx.doi.org/10.1016/j.cell.2013.11.037

Rodman, C. et al. (2016) In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells. Leukemia. doi:10.1038/leu.2016.344.

Mazin, A. V. et al. (2017) Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair. Molecular Cell. DOI: http://dx.doi.org/10.1016/j.molcel.2017.05.019.

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