Engineering Greater Radiation Resistance may well Lead to a Slowing of Aging

While I suspect that improvements in energy management coupled with magnetic field technologies are the cost-effective way forward when it comes to engineering defenses against radiation for space travel, it is certainly possible to consider classes of biomedical solution that could in principle greatly improve resistance to radiation in mammals. Insofar as that would require an improved capacity for cells to manage and repair oxidative damage and DNA damage, it seems likely that success would lead to treatments and enhancement biotechnologies that also slow the progression of aging.

The degree of slowing, and how it breaks down into cancer resistance versus other aspect of aging, depends on the degree to which DNA damage and oxidative damage are important in normal aging, versus the contributions of other causes and processes. The evidence of recent decades doesn't provide sufficient support for a definitive view on this topic. That will continue to be the case, I suspect, until such time as effective ways to repair or remove individual contributions to aging in isolation from one another are developed and extensively tested. So far theory and inspection have proven poor approaches to the production of good numbers for the relative contribution of specific processes to the progression of aging. Our biology is too complex to make much headway towards these detailed answers via analysis without intervention at the present time.

While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments. The main components of space radiation are solar particle events (SPE), geomagnetically trapped radiation, and galactic cosmic radiation (GCR). The contribution of the first two to the total dose absorbed by astronauts would obviously be negligible on long-duration missions away from Earth and the Sun. Consequently, GCR consisting mainly of highly-energetic particles would be the primary type of radiation encountered by humans under this scenario. It has been estimated that a return trip to Mars could subject astronauts to radiation doses of 660 mSv. Although great uncertainties exist with respect to health (cancer) risk estimates from exposure to cosmic radiation, this dose alone represents more than half of the total NASA astronaut career limit.

In principle, ionizing radiation interacts along charged particle tracks with biological molecules such as DNA. The process is largely stochastic, and can damage DNA via direct interactions or via indirect interactions such as through the production of reactive oxygen species (ROS). Radioresistance denotes the capacity for organisms to protect against, repair and remove molecular, cellular, and tissue damage caused by ionizing radiation. It is a quality that varies greatly in terms of effectiveness between different organisms. For instance, it is well-known that certain organisms are remarkably resistant to the damaging effects of radiation. The bacterium Deinococcus radiodurans, for instance, possess error-free DNA repair mechanisms and can withstand doses as high as 7 kGy. Similarly, tardigrades can withstand doses as high as 5 kGy, though doses exceeding 1 kGy render them sterile.

All eukaryotic organisms have evolved against a backdrop of constant exposure to endogenous and exogenous mutagens, and as such have developed robust cellular mechanisms for DNA repair and protection against DNA damage. Substantial experimental evidence suggests that low-dose radiation may trigger a variety of protective responses within cells, tissues and organisms that serve to protect them from both exogenous (e.g high doses of radiation) and endogenous (e.g. age-related accumulation of DNA damage) genomic instabilities. Importantly, these responses, collectively termed radioadaptive responses or radiation hormesis, may protect against spontaneous or induced cancer.

Genome instability resulting from DNA damage and mutation in both nuclear DNA and mitochondrial DNA caused by replication errors and exposure to endogenous and exogenous mutagens has long been implicated as one of the main causes of aging. All strategies for enhancing radioresistance in humans, from the expression and overexpression of exogenous and endogenous DNA repair genes, antioxidants, and ROS scavengers, to the expression of exogenous radioprotective genes, would also serve as a means of attenuating DNA damage and mutation implicated in eukaryotic aging. As such, strategies for enhancing radioresistance in humans would also constitute a promising geroprotective strategy and a means of attenuating aging and promoting longevity and extension of both lifespan and healthspan in humans as well.

Link: https://doi.org/10.18632/oncotarget.24461

Comments

Our primitive medicine: It has been well known since at least the 1950s that the majority of the damage from ionizing radiation is from the chemical soup created from the interaction of the high-energy charged particle (betas and alphas) or high energy photons (gamma rays) with tissue. It has also been known for decades that "anti-oxidants" can facilitate the clean up of this mess. Have you ever seen a sign posted, or a pamphlet handed out at a medical radiation facility (imaging or treatment) telling people they should take some extra vitamin C or any of the far more powerful anti-oxidants easily available ( https://www.superfoodly.com/orac-values/ )? Even when I mention it to the medical techs running the machines or doctors ordering the procedure, I almost always get blank stares.

You should know: Back in the early part of the 20th century, the Rockefellers bought up and closed essentially all the hospitals in the United States focus on health care rather than sick care ( https://worldaffairs.blog/2015/10/20/how-rockefeller-founded-modern-medicine-and-killed-natural-cures/ ), while at the same time establishing the standard curriculum that MDs receive. The fact that doctors know little about, and do not inform their patients about the effects of radiation and what to do about it is part of this legacy. Fortunately, most physicists are well aware and don't need some 2nd year physics drop out to pre-med telling them. We tell our friends and families...and readers of this blog in this case.

I am waiting for an enterprising mal-practice lawyer to sue the pants off of the medical radiation equipment industry and/or one of the large imaging or treatment providers for this negligence.

Posted by: Tom Schaefer at March 29th, 2018 8:39 AM

My thought is that we need more than the basic antioxidants to offset the damage of ionizing radiation. We need activated sirtuins, activated FOXO3A, and activated repair genes, etc. that can repair the single and doubled-stranded DNA breaks that are accelerated by ionizing radiation. For the Sirtuins, we especially need activated SIRT1, SIRT3 and SIRT6. Resveratrol and quercetin are needed to activate the sirtuins and DNA repair genes. Plenty of NAD+ is needed to provide high levels of energy to drive DNA repair genes. In addition to activated FOXO3A, we need activated PARP1 and BubR1 to repair the double-stranded DNA breaks. Also, it should be noted that the right mixture of gene activators is needed to activate the endogenous antioxidants glutathione, SOD2, etc.

Posted by: Biotechy at March 29th, 2018 11:20 AM

PS: The basic antioxidants Vitamins, A, C, and E are good for fixing single-stranded DNA breaks, but will do nothing to fix the double-stranded breaks. Magnisium is needed to fix the R-loop mutations. Other endogenous antioxidants that are useful in DNA repair include catalase and bilirubin.

Posted by: Biotechy at March 29th, 2018 12:44 PM

There is plenty of scientific evidence supporting the case for DNA damage being a primary determinant in aging, and there is also data to support why it is not. These fundamental questions are critically important to answer soon so that we can move towards consensus. I believe that time is coming soon as do many of the researchers who were at Undoing Aging.

Posted by: Steve Hill at March 29th, 2018 2:17 PM

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