Jumping Genes and Longevity

We can see how genetics play a role in how long we live. Looking at different species and how long or short they live. But we do not know exactly how this works.

Alexander Graham Bell, the inventor of the telephone, was more passionate about aging. In 1900s he found that people that lived long had long-lived children. Whether this is due to genetics or to providing support to children, or both, remains undefined. But the connection is there. Sometimes despite having the best genes, bad luck just strikes. Take the example of Jeanne Louise Calment, who died at the age of 122 years in 1976. Despite having the best genes for longevity her family did not enjoy these positive attributes. Sometimes bad luck negates good genes when her daughter Yvonne, died at age 36 of pneumonia. Luckily, she left a son Frederic, who became a physician. He lived with his grandmother in her apartment. However, he also died early,  in a motorbike accident, at the same age as his mum 36 years old. Sometimes bad luck negates any genetic advantages.

Three classic experiments define how a genetic advantage results in living longer. The first experiment was conducted by Michael Rose who by allowing only eggs of older flies to hatch he found that the next generation lived longer. The new generation seemed to know that, similar to their parents, they need to live longer in order to reproduce. We also find this among humans. The older your mother was when she conceived you, the longer you will likely live. Unlike human, there is no nurturing for flies, so this effect is predominantly genetic.

The second type of experiment uses a naturally occurring disorder in a flatworm that produces less growth hormone which stunts their growth but they end up living much longer. Through a series of trial and errors Cynthia Kenyon at University California San Francisco managed to chemically knock out one of these genes in normal flatworms and in so doing nearly doubling their lifespan.

The third type of genetic observation is seen with mice, in particular the work done by Richard Miller and his infamous dwarf mouse called Yoda. Again, nature lead the way in showing us about the longevity advantage of having less growth hormones. In nature there are three types of dwarf mice that share this longevity characteristic: Snell, Ames and Laron dwarf mice. These mice live about three times longer than average.

By knocking out a gene to stop growing larger we could all live longer. Somehow the body knows that we need to live longer in order to be able to pass on its genes. Fortunately, we also have examples among humans as well. In a southern Ecuador community of 250 individuals that have Laron syndrome—causing a deficiency in primary growth hormone—although protecting them against disease, especially cancer, this apparent protection does not translate to living longer. This group unfortunately engage in risk behaviors in particular alcoholism that negate this genetic advantage.

No one wants to have a stunted growth in order to live longer. But what about having older parents to increased longevity? In biology, there is always a dark side—known scientifically as antagonistic pleiotropy.  This construct has plagued gerontological research since it posits when one gene controls for more than one trait (e.g. height) it is likely that one of these traits is beneficial (e.g. more athletic) while another side is detrimental (e.g. heart disease) to the individual later on in life.

The dark side is that we know that women having children at much older ages increases the risk of certain genetic problems. It has also been reported in 2018 by Boris Rebolledo-Jaramillo with Nottingham-Trent University UK, and his colleagues that children of older mothers face greater risk of developing diabetes, dementia and heart disease. As for older fathers, their kids are more likely to have dwarfism or Apert syndrome.  Newer research in 2012 by Augustine Kong at Reykjavik University, Iceland also suggest that there is an increased risk for autism and schizophrenia. There is a “goldilocks effect”, not too old and not too young, just right.

The surprising result in genetic research is the finding that as we age we are also changing our genes. It was always assumed that our genes unchanging and that they are given to us exclusively by our parents, period. But we are learning that we also add and modify our genes as we age. We acquire one percent of our genes from bacteria, fungi, viruses and archae—single cell micro-organisms.  Specifically, there are special molecules that reside in these cells that are there specifically to develop antibodies. They are not part of the cell but act as independent contractors. Known as “plasmids” they help us fight infections. If we are constantly being infected, in order to help us develop immunity, they somehow insert their antibodies-producing-genes into our DNA so we can develop this protection ourselves. Sometimes our own genes change position in our chromosomes so they gain higher priority. These genes are known as “jumping genes” or as “transposons.”

Such strange genetic behavior was first discovered by Barbara McClintock in the 1940s who was awarded the Nobel Prize for medicine in 1983. How plasmid and jumping genes do this remains an absolute mystery. Her work provided evidence that the composition of our genes—our genome—changes while we are living. The longer we live, the more likely that these new genetic improvements are transmitted to our children. So now we have figured out the method of how Michael Rose’s flies create a time stamp on their genes. Plasmids are at work throughout the aging process.

We develop immunity from the day we are born and some of these biological adaptations end up in our genes through the transfer of external genetic material. Our genes are more permeable than we once thought. We get genes not just from our parents but also from the environment. In addition, we also get genetic material from our twins in the womb and mothers get genes from their children. We find male chromosomes in mothers who had baby boys. We are a magnet for adaptive genetic material from our environment.

Barbara McClintock was also the first scientist to correctly speculate on the basic concept of how some genes can be switched on and off—known as epigenetics, epi meaning “above” controlling genes. Sometimes a defective gene (e.g. for diabetes or Alzheimer’s disease) can be switched off—through diet, exercise and mild trauma. As we age we pick up new genetic material and modify existing genes (epigenetics) before we pass these genes on to our children. Our lives are devoted to just this aim, making sure that our children are best prepared to the new world they face. As for bad luck, we have Pandora’s last remaining attribute: Hope.

© USA Copyrighted 2018 Mario D. Garrett

References

Bartke, A., Wright, J. C., Mattison, J. A., Ingram, D. K., Miller, R. A., & Roth, G. S. (2001). Longevity: extending the lifespan of long-lived mice. Nature, 414(6862), 412.

Garrett M (2017) Immortality With a Lifetime Guarantee. Createspace.

Kenyon, C., Chang, J., Gensch, E., Rudner, A., & Tabtiang, R. (1993). A C. elegans mutant that lives twice as long as wild type. Nature, 366(6454), 461.

McClintock, B. (1993). The significance of responses of the genome to challenge.

Accessed:https://www.nobelprize.org/nobel_prizes/medicine/laureates/1983/mcclintock-lecture.pdf

Rebolledo-Jaramillo, B., Su, M. S. W., Stoler, N., McElhoe, J. A., Dickins, B., Blankenberg, D., ... & Paul, I. M. (2014). Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA. Proceedings of the National Academy of Sciences, 111(43), 15474-15479.

Rose, M. R. (1984). Laboratory evolution of postponed senescence in Drosophila melanogaster. Evolution, 38(5), 1004-1010.