In your opinion, why does biological ageing occur?

This article was written by Nguyen Do Quy Linh, a 17-year-old student from Vietnam who was the winner of the Sciencious STEM Writing Competition. Linh chose to write about the topic “In your opinion, why does biological aging occur” and fought off fierce in her topic category, competing against nearly a hundred of submissions for the Sciencious Competition. Congratulations to Linh!

Extending longevity substantially has been an ambition of humans for a long time. In order to realize this dream, people first need to explore the root causes and mechanisms of biological ageing, and then find ways to delay or reverse this natural and inevitable process. To clarify, unlike chronological ageing which “simply indicates the time passed since birth”, biological aging “refers to the decline in tissue/organismal function” (Hamczyk, 2020, p.921). At the present, there are numerable theories accounting for ageing, both in mechanical and evolutionary aspects. In this essay, I will hypothesize that deterministic genes regulate ageing, with cumulative random damages to somatic cells as intermediaries to express ageing phenotypes.

In the mechanical aspect, which addresses the question “How do we age?”, the pool of thoughts is polarised into stochastic theory, which states that random accumulation of damage leads to ageing, and non-stochastic theory, which claims that certain genes control this process. Theformer category points to the unavoidable cumulative deterioration as a side effect of the natural process of development in the species. Somatic DNA mutation theory and free radicals theory are a case in point. According to the first one, several genes can be copied inaccurately during cell division, some of which can be repaired but not all. These remaining impaired genes accumulate and cause cellular malfunction, inducing ageing process. In terms of free or oxidative radicals, which are by-products of biochemical reactions in metabolism, they can easily bind with other molecules, creating the imbalance within such molecules and hence warping DNA and cell functions. Reducing the oxidative damage has proved to extend the lifespan of some model yeasts and fruit flies (Fontana et al., 2010). Non-stochastic theory, by contrast, asserts the existence of genes that determine the lifespan of a species and regulate the ageing process. For example, artificial mutation of a single daf-2 gene in C. elegans has doubled the lifespan of it
(Kenyon et al., 1993). A possible mechanism of the theory is that nucleus genomes programme a decline in bioenergetics, ultimately resulting in cell senescence, or the stop of cell mitosis after 40-60 divisions (Trubitsyn, 2020). Also known as Hayflick limit, the cell senescence is believed to be the ageing clock of the body.

To substantiate these mechanisms, it is crucial to consider evolutionary regulation that may respond to the question “Why do we age?”, especially when ageing and death are seemingly against natural selection for the individual and might not have been selected for during evolution. Scholars often take a stance between non-programmed and programmed theory by natural selection. The first one, also known as evolutionary senescence theory of ageing, posits that organisms do not need to live beyond a species-specific age, hence not retaining the capability to do so. To elaborate, since organisms are less likely to survive the old age due to harsh environments, natural selection prefers the genes that are beneficial in early life but neglects those that are harmful in later life to promote reproduction at early age (Medawar, 1952, as cited in “Theories of Ageing”, 2016). By doing this, individual benefits are preserved at least until reproduction is done. On the contrary, programmed theory suggests that animals are proactively programmed to die at a certain age for the sake of the species population (Weismann, 1889, as cited in Chmielewski, 2017). This hypothesis aligns with group selection, in which a disadvantage (death) of an individual can be seen as altruism to the population because it makes way for those who are younger, more exuberant and capable of reproduction, thus facilitating the permanent survival of that species. Moreover, finite longevity can evoke evolution as a consequence of generation alternation. However, group selection and evolvability remain controversial because the short-term individual benefit tends to outweigh long-term group benefit. As a result, the programmed theory has yet to be widely approved among researchers.

All things considered, I find a compatibility between the two evolutionary theories and the non-stochastic mechanical theory. The programmed evolutionary theory seems to be the driving force behind non-stochastic theory, as genes controlling ageing are designed to ensure the physical deterioration until a species-specific age, serving the purpose of group selection. Even if programmed theory is disputed, doesn’t evolutionary senescence theory of ageing also acknowledge the role of genes in contributing to ageing? Being either deliberately programmed by nature or an inevitable side-effect of selection favouring early life, ageing is still regulated by genes. This poses the question if stochastic and non-stochastic theories can simultaneously be the basis of ageing, but the latter as primary cause and the former as secondary cause. As presented in the paragraph about mechanism of ageing, genetic control decreases bioenergy, which in turn prompts various destructive processes in physiological, biochemical, and biophysical function within the organism’s body. These damages are indeed stochastic and not directly under genetic elements (Trubitsyn, 2020). The explanation can account for the variation in lifespan among different species due to the deterministic genes that control longevity, that is, the same organisms in a species have approximately the same lifespan. In addition, this also illuminates why genetically similar organisms in the same environment age differently by involving stochastic damages in cells and organs (Gladyshev, 2016). For instance, while one person (or mouse)
suffers death from heart failure, another may succumb to cancer without having cardiac dysfunction (“Theories of Aging”, 2016). Overall, as organisms become older, specific genes dictate the direction of deterioration and random damages occur, accumulate and weaken cellular
function.

In conclusion, I believe that genetic control orchestrates ageing, and stochastic damages are direct factors in creating the phenotypes of old age. In terms of evolution, it is hard to fully justify either of the programmed and non-programmed theories, but both of them to a certain extent support the mechanical genetic-control theory. All of afore-mentioned analysis
notwithstanding, further research and exploration are essential to generate an optimal explanation for ageing, which can open limitless potential applications in enhancing lifespan.

References

Chmielewski, P. (2017). Rethinking modern theories of ageing and their classification: the proximate mechanisms and the ultimate explanations. Anthropological Review, 80(3), 259-272. https://sciendo.com/pdf/10.1515/anre-2017-0021

Fontana, L., Partridge, L., Longo, V. D. (2010). Extending Healthy Life Span—From Yeast to Humans. Science, 328(5976), 321-326. https://doi.org/10.1126/science.1172539

Gladyshev, V. N. (2016). Aging: progressive decline in fitness due to the rising deleteriome adjusted by genetic, environmental, and stochastic processes. Aging Cell, 15(4), 594–602. https://doi.org/10.1111/acel.12480

Hamczyk, M. R., Nevado R. M., Barettino, A., Fuster, V., Andrés, V. (2020). Biological Versus Chronological Aging. Journal of the American College of Cardiology, 75(8), 919-930.
https://doi.org/10.1016/j.jacc.2019.11.062

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), 461–464. https://doi.org/10.1038/366461a0

Theories of Aging (2016). American Federation for Aging Research.
https://www.afar.org/imported/AFAR_INFOAGING_GUIDE_THEORIES_OF_AGING_2016.pdf

Trubitsyn, A. G. (2020). The Mechanism of Programmed Aging: The Way to Create a Real Remedy for Senescence. Current Aging Science, 13(1), 31-41.
https://doi.org/10.2174/1874609812666191014111422

Featured image retrieved from: https://www.hindustantimes.com/health-and-fitness/what-s-the-difference-between-chronological-age-and-biological-age/story-LzUWZXGpk83kNtlCaFqu7O.html

Nguyen Do Quy Linh

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