Ageing is the most common phenomenon occurring around us and is presently perpetual. Ageing is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas, for example, bacteria, perennial plants, and some simple animals are potentially biologically immortal. This is a rather junky and unscientific definition of ageing.
According to many biogerontologists, ageing can be portrayed more scientifically and simply. Our cellular metabolism corresponds to everything, allowing us to live from one day to the next and making our cells function. Over time, this metabolism accumulates damage intrinsically related to its operation, which is not without errors. This damage then causes pathologies and causes us to age.
The critical issue is not the specific metabolic processes that lead to ageing damage but the damage itself. Forty-year-olds have less healthy lifespan than twenty-year-olds because of the molecular and cellular makeup differences, not because of the underlying mechanisms.
For centuries, people have been trying to live longer. In the past, there were two main approaches to longevity. One course was to focus on extending the lives of elderly people. This was the approach of the 16th to 18th centuries when people believed that old age was a time of worth and vitality. They worked to improve the health and well-being of elderly people, and developed treatments for age-related diseases.
The other approach to longevity was to focus on preventing ageing altogether. This was the approach of the 19th and early 20th centuries when some people began to see old age as a disease to be eliminated. They devised many procedures to prevent ageing, such as blood transfusions, hormone treatments, and surgery.
The modern anti-ageing movement is similar to the longevity movement of a century ago. Both groups see old age as a disease and believe it can be cured through medical interventions. They also argue that the elderly are an economic burden.
However, the modern anti-ageing movement also differs from the longevity movement of a century ago. The modern movement focuses more on individual interventions, such as hormone therapy and cosmetic surgery. Some anti-ageing treatments we use today can be traced back to ancient Egypt.
Ageing is a significant cause of death worldwide. Every day, around 150,000 people die, and two-thirds of them die of ageing. Ageing is responsible for around 90% of deaths in the industrialised world.
Defeating ageing is about extending lifespan and eliminating the “grim years of debilitation and disease” that currently end most people’s lives. Defeating ageing would actually eliminate the period of old age altogether. This would be achieved by postponing the onset of old age to indefinitely greater ages so that people never reach it. In other words, there would be no elderly population, as everyone would remain healthy and youthful until they died. The elimination of ageing would have a significant financial impact. The average person in the industrialised world consumes more healthcare resources in their last year of life than in their entire life up to that point. This means that eliminating the final year of life would save trillions of dollars per year.
Immortality may sound too complicated and challenging to achieve. But, it might be easier than assumed by many people. Ageing can be compared to a car wearing down. As the body operates normally, it accumulates damage, which can be tolerated to an extent, but eventually sends us into a steep decline. The most promising way to escape this biological reality is to repair the damage as needed with precise scientific tools. This method to tackle ageing focuses on an engineering approach, which aims not at prevention but pure and straightforward treatment of ageing. Ageing is a biological phenomenon that can be understood through the lens of physics. The exact process occurs in the human body as in a car, aeroplane, or any other machine with moving parts. The goal is to preserve the molecular and cellular structure of the body to how it is in early adulthood.
Cellular damage can be classified into seven interconnected parts. These seven causes have remained unchanged since the early 1980s, meaning little is yet to be discovered in this area. This is reassuring because it limits us to a few well-defined mechanisms.
- Intracellular Waste
- Intercellular Waste
- Nuclear Mutations
- Mitochondrial Mutations
- Stem Cell Loss
- Increase in Senescent Cells
- Increase of Intercellular Protein Links
We have pinpointed the seven underlying mechanisms of ageing, and we are close to being able to intervene at the point of cellular damage. If prevention is not viable, we can treat the ageing of our cells. We, in fact, have a potential solution for all the above-mentioned problems. It concentrates on regenerative approaches to anti-ageing medicine, which are technologies that can restore tissues’ typical structure and function after damage.
This article will focus on stem cell loss and how to address it.
Stem cells are undifferentiated cells that can give rise to specialised ones. They are found in all multicellular organisms, including humans. Stem cells are essential for the development and repair of tissues and organs. As we age, we gradually lose cells that are essential for our health. This can lead to various diseases, including Parkinson’s disease, caused by the loss of cells in the brain. Stem cell research offers the possibility of recreating these missing cells, which could be used to treat ageing-related diseases.
Embryonic stem cells are the most well-known type of pluripotent stem cell. Given the right biochemical signals, embryonic stem cells can be induced to become any type of cell in the body. These differentiated cells can be used to repair or replace cells and tissues lost due to disease, including debilitating diseases that are difficult to treat, such as many of the worst effects of ageing. The net loss of cells is a significant factor in ageing, and stem cell research offers the potential to mitigate this damage. However, there are ethical difficulties regarding the use of human embryos, as well as the problem of tissue rejection following transplantation in patients.
Induced pluripotent stem cells (iPSCs) are a type of stem cell that can be created from adult cells by reprogramming them to an embryonic-like state. Induced pluripotent stem cells (iPSCs) are very similar to embryonic stem cells (ESCs) in many ways. They have similar shapes and growth patterns and are equally sensitive to the same growth factors and signalling molecules. Like ESCs, iPSCs can differentiate in vitro into cells from all three germ layers: ectoderm, mesoderm, and endoderm. When injected into immunodeficient mice, iPSCs can also form teratomas, tumours containing cells from all three germ layers. This was first achieved in 2006 by Shinya Yamanaka and Kazutoshi Takahashi, who showed that introducing four specific genes (Myc, Oct3/4, Sox2, and Klf4) into adult cells could turn them into iPSCs. These genes are known as the Yamanaka factors. These can also be created in a patient-matched manner, meaning that each individual could have their own pluripotent stem cell line.
iPSCs are typically generated by introducing the products of specific sets of genes associated with pluripotency, also known as “reprogramming factors”, into a given cell type. These factors were identified by hypothesising that genes essential to embryonic stem cell (ESC) function might be able to induce an embryonic state in adult cells. Hence, twenty-four genes previously identified as necessary in ESCs were chosen and delivered to mouse fibroblasts using retroviral transduction. A retrovirus vector is an infectious virus that introduces a nonviral gene into mitotic cells in vivo or in vitro. To identify the genes necessary for reprogramming, the researchers started with a pool of 24 genes and removed one gene at a time. By doing this, they could identify four genes, Oct4, Sox2, cMyc, and Klf4, that were each necessary and sufficient to generate ESC-like colonies under selection for reactivation of Fbx15.
In November 2007, two independent research groups reported the successful reprogramming of human cells into induced pluripotent stem cells (iPSCs). The first group, led by Shinya Yamanaka of Kyoto University in Japan, used the same four genes (Oct4, Sox2, Klf4, and cMyc) that had been used to reprogram mouse cells. The second group, led by James Thomson of the University of Wisconsin-Madison, used a different set of four genes (Oct4, Sox2, Nanog, and Lin28). Both groups used a viral vector to deliver the genes into the human cells.
In the first works on murine and human iPSC production, either retro– or lentiviral vectors were used for the delivery of Oct4 , Sox2 , Klf4 , and c–Myc genes into somatic cells. They are very efficient at transducing cells, meaning they can insert their genetic material into the host cell’s genome. This is important because it allows the retroviral vector to deliver the genes needed to reprogram the cell into an iPSC. In addition, retroviruses are terminated in pluripotent cells. This means that the transcription of the retroviral genes is stopped once the cell has been reprogrammed. This is another important feature because it helps to prevent the cells from becoming cancerous.
However, using retro- and lentiviral vectors for iPSC production has several limitations. First, retroviral DNA is randomly integrated into the host cell genome, which can lead to insertional mutagenesis and tumour formation. Second, the transcription of exogenous Oct4, Sox2, Klf4, and c-Myc genes can resume in the cells derived from iPSCs, which can also lead to tumour formation. Lentiviruses can also integrate into the genome and maintain their transcriptional activity in pluripotent cells. To avoid these problems, promoters controlled by exogenous substances added to the culture medium can be used to regulate the transcription of transgenes. However, this approach can be technically challenging and only feasible for some cell types.
Another problem is the gene set itself used for the induction of pluripotency. The ectopic transcription of Oct4, Sox2, Klf4, and c-Myc can lead to neoplastic development (tumour formation) from cells derived from iPSCs. Therefore, alternative gene sets less likely to promote tumour formation are being investigated.
One can confidently state that both iPSCs and their derivatives are potent instruments applicable in biomedicine, cell replacement therapy, pharmacology, and toxicology. However, the safe application of iPSC–based technologies requires the use of methods of iPSCs production and their directed differentiation, which minimise both the possibility of mutations in cell genomes under in vitro culturing and the probability of malignant transformation of the injected cells.
Some therapies are already well advanced and may soon lead to clinical trials. Hence immortality is not as far as it might seem to be. According to some scientists, humans have a 50–50 chance of achieving immortality within 20 years, and there is also a 10% chance that we won’t get there for a hundred years. Defeating ageing is not just a future industry; it’s an industry now that will be both profitable and extremely good for your health. The good thing about gerontology is that it will still have benefits even if it fails to make humans immortal. It can ease people’s way through old age by treating and eventually preventing age-related diseases.
- Yang Li et al., A programmable fate decision landscape underlies single-cell aging in yeast. Science369,325–329(2020).DOI:10.1126/science.aax9552
- Zhen Zhou et al., Engineering longevity — design of a synthetic gene oscillator to slow cellular aging.Science380,376–381(2023).DOI:10.1126/science.add7631
- “Anti-Aging Medicine: The History Life Extension and History: The Continual Search for the Fountain of Youth.” 2016, http://biomedgerontology.oxfordjournals.org/content/59/6/B515.full.pdf
- Anti-Aging Pioneer Aubrey de Grey: “People in Middle Age Now Have a Fair Chance”. https://lifeboat.com/blog/2018/02/anti-aging-pioneer-aubrey-de-grey-people-in-middle-age-now-have-a-fair-chance
- Transhumanism: Aubrey de Grey’s causes of aging and how to stop them — Work for human longevity. http://www.longlonglife.org/en/transhumanism-longevity/transhumanism/transhumanism-aubrey-de-greys-causes-of-aging-with-sens-foundation/
- Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R (November 2006). “Human embryonic stem cell lines derived from single blastomeres”. Nature. 444 (7118): 481–5. Bibcode:2006Natur.444..481K. doi:10.1038/nature05142. PMID 16929302. S2CID 84792371
- Carole Haber, Anti-Aging Medicine: The History: Life Extension and History: The Continual Search for the Fountain of Youth, The Journals of Gerontology: Series A, Volume 59, Issue 6, June 2004, Pages B515–B522, https://doi.org/10.1093/gerona/59.6.B515
- Medvedev SP, Shevchenko AI, Zakian SM. Induced Pluripotent Stem Cells: Problems and Advantages when Applying them in Regenerative Medicine. Acta Naturae. 2010 Jul;2(2):18–28. PMID: 22649638; PMCID: PMC3347549.
- Cepko C, Pear W. Overview of the retrovirus transduction system. Curr Protoc Mol Biol. 2001 May;Chapter 9:Unit9.9. doi: 10.1002/0471142727.mb0909s36. PMID: 18265289.
