Scientists have managed to reverse aging in human skin cells by rejuvenating them a staggering 30 years. To understand how researchers managed this astonishing feat we must first understand a few concepts.
How do we age?
Have you ever wondered about the natural process of aging and the complexities behind it?
In simple terms, aging is defined as a continuous and progressive process of natural alteration that begins early in adulthood.
A key nuance remains essential, in fact, it is crucial to know how to distinguish normal aging and its effects from those of diseases. It is in this sense that the World Health Organization[1] divides the latter into three major stages according to age groups including 60-75 years, 75-90 years and over 90 years based on natural processes.
The extensive research on this subject and the resulting advances have made it possible to recognize the important role of genetic factors, alterations in cellular functioning or in the systems of protection against oxidation, or the role of modifications in protein metabolism such as non-enzymatic glycation.
From a purely biological point of view, ageing starts between the twenties and thirties according to certain studies. At the origin of this is senescence, a physiological process that leads to a slow degradation of the cell’s functions. Physiological aging is manifested by a progressive loss of tissue homeostasis that can impact the physiology of organs and lead to the emergence of pathologies. All these elements added to the environmental factors that each being must face characterize the undeniable and natural cycle of life leading to the old age of an individual often made complicated by certain diseases more or less serious.
Can we measure age?
First of all, how is rejuvenation measured, i.e. how can you measure aging?
To measure age we often use a so-called epigenetic clock test[2], based on the early discoveries of S.Horvath, which measures the level of DNA methylation. Methylation is an epigenetic factor used by the cells, which affects gene activity and expression. An example of methylating regulation could be a methyl group located on a promoter which would inactivate the gene. This mechanism is also what partly makes cell differentiation possible, by choosing what genes are active for a certain cell.
Our cells are constantly replicating and getting subjected to DNA damage over and over. So naturally, reparation and replication of the DNA are needed. In these processes, epigenetic markers are a hindrance and therefore need to be removed. The disruption and reassembly of the epigenome are mediated by small interference RNA (siRNA)[3]. But as we get older this system starts to crumble and the reassembly is not perfect so mistakes are made. It is these errors and the accumulation of them, that are measured and quantified to determine your age.
Reprogramming cells vs reversing ageing in cells
The process used here builds on the work of Nobel prize Shinya Yamanaka 2012[4] induced pluripotent stem cell reprogramming. Yamanaka was able to reset many age-associated changes such as telomere shortening, and damage resulting from oxidative stress and most interestingly reset the epigenome of an adult cell. By applying his method he was able to turn specialized cells back into stem cells that can adopt any function.
However, with this method, the cells’ original identity is lost. It would be problematic if the same gene therapy were to be applied to a complex cell structure since the cells would not be able to recollect their roles. For example, if we applied the treatment to an old/sick eye, it would entirely lose its remaining function and turn into a tumor. But this discovery suggests that there are ways to reset your epigenome, and could play a central role in reversing aging
The new method of maturation phase transient reprogramming[5], MPTP, is very similar to the method used by Yamanaka with the difference being that the treatment is halted right before the stem cell state is reached, which allows it to retain its specialized function. By measuring the age with a novel epigenetic clock both before and after the treatment scientists were able to deduce that the biological age had been rolled back by 30 years, incredible!
Scientists are still working on understanding the mechanism behind MPTP
What is it useful for? [6]
Today, chronic diseases, to which older people are particularly susceptible, are the leading causes of death in the world. Slowing down the aging process can help prevent disease by reducing the risk of type II diabetes and heart disease, and giving us the opportunity to live to be 100 years old without worrying about getting cancer or Alzheimer’s disease. It sounds as simple as a reset button that instructs the body to become young again. It could also be the obvious alternative to plastic surgery and its few risks. We know that treating singular pathologies and care in general remain a very expensive affair. Targeting aging is more worthwhile: if we can slow it down, people will be stronger and less prone to diseases, which will avoid massive health costs.
Ethic in consideration
Aging remains a process that many people want to avoid at any cost, for example by buying products promising to rejuvenate your skin or by opting for plastic surgery. The emergence of reversing aging is an addition to this idealization of the young and healthy man, but without forgetting the many questions and concerns it raises.
Aging and its alteration remains a young and promising subject of scientific research. With today more than 300 theories explaining this process according to the Russian gerontologist Zhores Medvedev[7], would it be possible to find one promising spectacular effects in this direction? All hopes are allowed in this booming sector. It puts the finger on the eternal debate on whether ageing should be viewed as a disease or a non-pathological process.
And if we succeeded to reverse it, then what would we die of? What if we could prolong good health, would this be applicable to the longevity of people who are already ill? What would be the impact on today’s society and the possible demographic explosion that this would entail? The eternal questions of ethically correct make the vision of the altering of aging perhaps anodyne?
Regardless of how ethically acceptable it may be, the 150 year old man[8] is certainly not for tomorrow, but perhaps for after tomorrow…
If you found this interesting check out this further reading material
References
- Seni, 2022 https://seni-france.fr/fr_FR/blog/les-nuances-du-vieillessement-1
- Patrick T Griffin, 2021 https://www.biorxiv.org/content/10.1101/2021.10.25.465725v1.full
- Marlyn Gonzalez and Fei Li, 2012 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329497/
- Kazutoshi Takahashi, Shinya Yamanaka, 2006 https://pubmed.ncbi.nlm.nih.gov/16904174/
- Diljeet Gill, 2022 https://elifesciences.org/articles/71624
- David Gems, 2011 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3001315/
- Sabine Giry, Silvia Pei, 2012 https://biofutur.revuesonline.com/article.jsp?articleId=16985
- Emily Willingham, 2021 https://www.scientificamerican.com/article/humans-could-live-up-to-150-years-new-research-suggests/
Jonatan Bertolozzi
Hello, I’m Jonatan!
I’m studying my 3rd year in the biotechnology program at Chalmers University. I have always been a curious guy and I like to explore new field and topics. So I really enjoy the engineering approach to iGem. My big passions outside of my studies are sports, economics and chess.
Leïla Ouhamma
Hi 👋🏼! I’m Leïla, I’m 21 years old and I’m a 2nd year student in Biology. I am interested in mathematics, biostatistics, microbiology and engineering studies. Besides that, I’m a fan of rock climbing, hiking and travelling, always ready for new experiences.