Do we choose senescence or eternal youth?

By Dave Armstrong - 20 Jan 2015 11:11:7 GMT
Do we choose senescence or eternal youth?

Never has any animal been so carefully nurtured, investigated and provided so much useful information for us. The humble and squashable fruit fly is the source of much more human knowledge than other lab rats like the Rhesus monkey. The mutants possible in the eyes, legs, wings, hair and every other part of the insect have provided researchers with medical, veterinary and other papers on every fruity topic you can think of! And now, the answer to eternal life, well almost!

Drosophila image; Credit: © Shutterstock

When Thomas Morgan began the lengthy research on Drosophila melanogaster, he can’t have known the potential of this tiny fruit fly. With his 1933 Nobel Prize, he gained his reward, but the animal flies on ---. It outcompetes its fellow lab animals in genetics simply because the generation time is so rapid. At the University of Bern(e) in Switzerland, Marisa M. Merino is the lead author of a paper that opens wide the age-old search for immortality. Named Elimination of Unfit Cells Maintains Tissue Health and Prolongs Lifespan, it appears in the journal,Cell.

The ancients thought the gods were immortal and always sought the trick of living forever. We are more concerned with prolonging our lives medically and this is where a gene in the fruit fly comes in. An allele called azot has been found to control the elimination of unhealthy unwanted cells. These cells were the only examples where azot activity was found, proving that its activation meant they were selected for elimination. The azot gene is required to programme cell death. Unwanted neurons and failing cells had obvious connections with azot activation. In these cases of genome content, many genes such as this one are found in vertebrates like ourselves as well as the invertebrate fly.

This allele could now feature in a human-based research interest by which we can hope to prolong life in the average person. We already live up to 100 years in some countries where health care is reasonable. This was the situation with human ageing gene research just a few years ago. The attraction of this azot allele could be a far healthier existence for these older members of society, without so many debilitating infections or even diseases. Without any azot alleles, flies had up to 20% of cells that were unhealthy, proving the genetic expression helped to eliminate them. Detecting pre-cancerous cells and preventing tissue and organ decay (due to the accumulation of unfit cells) are likely to be just two of the functions of the azot allele. In other species, the same effects could be expected, although a lot of work is needed to verify any other effects of the whole genome or simply this one gene on other parts of the metabolism.

Heterozygous azot flies have only one azot allele of the normal gene pairs. These animals delayed cell death, proving an extra azot allele is useful. So a homozygous fly (2 azot alleles) was proved to have enhanced viability. They had no wing defects and these defects could actually be rescued by adding 2 copies of azot::dsRed! Again, when larvae were exposed to UV light, there was a suggestion that azot-expressing cells had been lost when the UV –induced mutations occurred. If the absence of azot accelerates tissue fitness decay in adults too, the brain (in the fruit fly) should develop neurodegenerative vacuoles where azot was not working. Did expression of azot increase the brain’s resistance to ageing and thereby extend life-span? The answer lay in the 7.8 day lifespan of flies lacking azot and the 12 day span of the +/+ azots. They lived for a maximum of 18 days or 24 with azot. Here lay the crux of the research: with 3 azot alleles (illegal in nature of course!), the age of the flies was extended even further, to a maximum of 28 days.

The research team, under the leadership of Eduardo Moreno, is carrying on, with a full knowledge that azot is necessary and sufficient in itself to slow ageing. It has the ability to select viable ells that make it critical for long lives in multicellular animals. Professor Moreno’s quote is ideal to complete our account as we wonder which species will be their next target: Our bodies are composed of several trillion cells and during aging those cells accumulate random errors due to stress or external insults, like UV-light from the sun. But those errors do not affect all cells at the same time and with the same intensity: Because some cells are more affected than others, we reasoned that selecting the less affected cells and eliminating the damaged ones could be a good strategy to maintain tissue health and therefore delay aging and prolong lifespan.