All living things must eventually grow old and die. This statement holds true for most animals as even the largest and most powerful of animals eventually grow old and die. This process is known as senescence or biological aging, and it follows a general format. First, the organism grows slower and weaker which is usually coupled with reduced fertility and lower rates of reproduction. The organism becomes less fit over time until its body can no longer continue functioning and it dies. However, some animals and even individual cells seem to ignore this rule and continue to live with no loss of fertility or reduction in physical function.
Animals, or cells who do this, are said to go through negligible senescence, or no measurable aging (Guerin, 2004). The extent of the negligible senescence that a given organism goes through varies, with some merely remaining active and fertile up until the point of death, while others do not die, unless they are killed or become diseased, and could be called biologically immortal. Humans even possess cells like this in the form of stem cells and cancer cells, though only one of those cell types is beneficial to the human. By examining these “immortal” animals and cells, it may even be possible to extend human lifespans greatly, or even remove aging entirely.
The first animal possessing the limited form of agelessness is the naked mole rat (Heterocephalus glaber). This species of rodent is almost completely blind and lives its entire life underground, yet has the longest lifespan of any rodent at nearly thirty years (Kim, 2011). Mole rats live in large underground nests, which they continuously expand and renovate throughout the life of the colony.
They seem more similar to ants than normal mammals, as they possess a queen which oversees the colony and is the only member of the colony allowed to breed. Queen or commoner, mole rats show no signs of aging at any point in their lifespan, remaining active right until death (Skulachev, 2017). Genetic analysis of the mole rat showed that they possess fewer repeated region than other rodents and mammals yet have a cancer rate lower than any other rodent and that does not increase as they age.
Among the genes found to be prevalent throughout the mole rat genomes were the genes TEP1 and TERF1, both of which controlled telomerase activity (Kim, 2011). TEP1 directed the encoding of subunits of the telomere and the TERF1 gene regulated the repeated sections of the telomere. Their gene families were found to contain many similar telomere directing genes as well. They were found to have less genetic diversity than any other rodent, which was compensated for by a higher number of gene transitions. These factors, all unique to Heterocephalus glaber, are believed to be the root of its longevity.
The naked mole rat was found to live longer than any other rodent, but it does still die of old age. Less complex animals, such as jelly fish and sponges, have developed ways to stave off aging entirely and can live until they are killed. This is due to the fact that they are considered “basal metazoans,” a group of animals that keep groups of stem cells within their bodies throughout their lives (Petralia, 2014). This gave many of them regenerative abilities, able to regrow limbs or in the case of a sponge survive being pushed through a metal sieve, which greatly increased their survivability in the wild and thus their longevity.
This mass of stem cells gives them something much more valuable than simply healing from mortal wounds, it allows them to replace their body cells with fewer mistakes. Most animals maintain their bodies through mitosis of their somatic cells, which involves the cell’s DNA being copied over and over again with mistakes being added each time. The basal metazoans central stem cells allowed them to replace somatic cells by copying straight from their stem cells, which hold an original copy of the animal’s DNA.
By allowing their stem cells to differentiate into the cell types needed instead of copying other body cells, the number of opportunities for genetic errors decrease significantly. As these accumulating genetic errors are the basis for death by aging, reducing or eliminating them allowed these simpler animals to live for extended periods of time. In fact the sponge is currently believed to be the animal with the longest lifespan. The spicules of a deep sea sponge where analyzed and it was found to be over 11,000 years old (Petralia, 2014).
Simple organisms have been alive and around far before humans and will likely still be around long after humans have died; however, they are not the only animals to have developed ways to slow aging. Many advanced mammals, humans included, slow aging by extending adolescence, a process called neoteny. The animals are allowed to grow more slowly, so more of their life was spent during the phase where their bodies are actively growing rather than maintaining (Skulachev, 2017).
While other apes have been found to possess some degree of neoteny, their death rates began climbing with age much earlier and faster than humans. This is important because once an organism has swapped from actively growing to reach sexual maturity to maintaining its adult body, it begins to accumulate genetic mistakes which cause a steady decline in bodily function. The axolotl also makes use of neoteny to live longer. While in their adolescent forms, their lifespans can extend past thirty years, with some estimates placing them even higher.
They are also capable of breeding while in their adolescent form, an unusual trait amongst most animals. If the water levels surrounding them are lowered enough, they permanently transition to their adult form which can survive on land but has a significantly shortened lifespan (Skulachev, 2017). Another species, the olm (Proteus anguinus), was similar to the axolotl in physiology, with the exception of its blindness due to the cave environments it inhabited. This species was also found to long lived, even more so than the axolotl, having a lifespan of sixty-two years with some estimates placing its lifespan at over one hundred years.
This species’ longevity was also due to neoteny and an adult form of the species has yet to be found in the wild (Skulachev, 2017). Part of the reason neoteny extends animals life spans has to do with the brain and how it develops. It was found that as the brain becomes more developed and complex, it becomes more vulnerable to oxidative damage and stress damage. By remaining younger for longer, animals like the naked mole rat can reduce the damage done to their brains, allowing them to live longer and more healthily (Skulachev, 2017).
Neoteny did allow more advanced animals to live longer, but there is a substance within every animal that could potentially give them negligible senescence, telomerase. Telomerase has been found to be responsible for coding telomeres, lengths of DNA with repeated sequences, and was responsible for determining how long a cell can live (Kim, 2002.) A small portion of DNA is lost every time a cell undergoes cell division.
At first the removal of this small piece of DNA had little effect, but as the divisions continued the lost portion of DNA grew larger and larger until the DNA could no longer code for the appropriate proteins, resulting in apoptosis. The telomere was the portion of the DNA that was cut first and protected the cells genetic material by being removed in its place.
In this way telomerase could be said to set the expiration date of a cell by the length of the telomeres that it added to the DNA (Kim, 2002). Telomerase was not found to be present throughout all the cells of organisms though. It was found only in germline cells and cancer cells, meaning that once the body cells undergo their first division, their telomere length is set and will only shorten as they continue to divide. This programmed cell death, or apoptosis, was discovered to be very important, as a cell that lives too long could mutate and cause the body harm (Counter, 1998).
When a mutation occurred at an oncogene, which normally helps with the cell’s growth, the oncogenes becomes permanently activated. If mutations also occur at the tumor suppressor genes, which kill the cell once it has become too mutated, then the cell’s genes for telomerase activates and it becomes immortal since it could maintain its own telomeres (Counter, 1998). A cell such as this, one that no longer experienced apoptosis, was then considered cancerous. Cancer cells are not affected by aging and continue to divide and multiply as long as nutrients are available, and eventually replace so much of the tissue they make up that it can no longer function as intended.
Immortality has been sought after by humans since our earliest fables and human lifespans have increased significantly over the past one hundred fifty years, but immortality has not been achieved yet. Through the study of animals and cells with negligible senescence, it could one day be achieved with the most likely route for this being genetic manipulation (Lucke, 2005).
By altering our DNA to have active genes for telomerase, apoptosis could be avoided. The next hurtle would be keeping this new immortal DNA from becoming cancerous, a feat most likely achieved by modifying the tumor suppressor genes. If the genes controlling human brain development were to be modified to be more like the naked mole rat’s, it would not only make the brain degrade slower, the occurrence of neurological diseases would also be reduced.
Only through continued research and experimentation can humans hope to achieve biological immortality. Immortality would not be without its downsides as people living longer means they consume more resources and continue to reproduce but unchecked by death. This could lead to overpopulation and shortages of necessary resources, which would likely result in increased armed conflict as potentially infinite people compete for finite resources (Lucke, 2005). As humanity approaches the precipice of biological immortality, they will need to be careful to ensure that achieving immortality does not result in more death and suffering than in the pre-immortal world.
References
- Counter, C. M., Hahn, W. C., Wei, W., Caddle, S. D., Beijersbergen, R. L., Lansdorp, P. M., … & Weinberg, R. A. (1998). Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proceedings of the National Academy of Sciences, 95(25), 14723-14728.
- Guerin, J. C. (2004). Emerging Area of Aging Research: Long‐Lived Animals with “Negligible Senescence”. Annals of the New York Academy of Sciences, 1019(1), 518-520.
- Kim, E. B., Fang, X., Fushan, A. A., Huang, Z., Lobanov, A. V., Han, L., … & Yim, S. H. (2011). Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature, 479(7372), 223.
- Kim, S. H., Kaminker, P., & Campisi, J. (2002). Telomeres, aging and cancer: in search of a happy ending. Oncogene, 21(4), 503.
- Lucke, J. C., & Hall, W. (2005). Who wants to live forever?. EMBO reports, 6(2), 98-102.
- Petralia, R. S., Mattson, M. P., & Yao, P. J. (2014). Aging and longevity in the simplest animals and the quest for immortality. Ageing research reviews, 16, 66-82.
- Skulachev, V. P., Holtze, S., Vyssokikh, M. Y., Bakeeva, L. E., Skulachev, M. V., Markov, A. V., … & Sadovnichii, V. A. (2017). Neoteny, prolongation of youth: from naked mole rats to “naked apes”(humans). Physiological reviews, 97(2), 699-720.