Something got me seriously thinking after attending a very interesting public lecture delivered by an erudite professor in which he critically discussed regenerative medicine in a more practical approach. During the course of the lecture, a lot went through my mind. Decided to do some research and I bumped into a research paper that attempted age reversal. Though not a new thing, but the advances that have been made thus far is indeed highly revealing of the potentials that there is in cell manipulations, as you read along, you will understand better. But wait, why and how do humans age? I think if we are able to understand the real cause of aging, then understanding its reversal (if really possible and reasonable) becomes easier to understand.
Humans and aging process
Generally speaking, aging is an inevitable process that must occur in all living thing creatures no matter how big or small however, with some few exceptions to this. It is a process that is part of the physiological process in life. Though this process can either be slowed down or hastened depending on a host of factors ranging from environmental, hereditary, epigenetic changes and even life style. One of the most common under the life style category is the feeding. What we eat greatly affects our overall health status.
Good feeding habit promotes longevity but still doesn't mean that we will live for ever. On the other hand, bad feeding habit shortens the life spans. All cells are programmed to die at a particular point in time and this mostly common in animals, mammals and other higher creatures like humans. In contrast to this, smaller creatures can be potentially immortal by producing replicate identical cells of themselves. Through this, they remain viable and alive for a years.
In a nutshell, we age as a result of accumulation of accumulation of changes in the form of damages over time. It is chronic process that actually begins the moment we are born and it continues until at a point where the cells come to a stand a still. I.e the cells loosing their regenerative ability thereby leading to a decline and loss of immuno protective functions. Commonly, the from what we eat, radicals such as reactive oxygen/nitrogen species are derived. These radicals cause oxidative damages to cellular activities of cells and at the long run, impair their biological and physiological functions.
Cells are the building block of all components of the humans body. As cells unite to form tissues, so do tissues unite to form organs. Multiple organs in turn makes up the complex body system. When the foundation of anything is weak or faulty, the whole structure comes crumbling down. This is just a simple example of how the human Body system is built. I will limit this discussion to cel death as a consequence of induced oxidative damages coming from radicals. This type is commonly referred to as cell death due to oxidative stress factors.
The visible and obvious effects of aging most times comes with diseases that ultimately lead to the death. When the liver for example is unable to carryout one of its most important role - detoxification of toxic metabolites of metabolism, these substances accumulate in the body and cause harm to other organs. The constellation effects leads to multiple organ failure that ranges from the kidney, pancreas, spleen, lungs and more. In this case, we could say that the aetiology of the disease is pathological.
Cells are programmed to die at some certain point in time, and when this occurs, it is referred to as physiologic cell death. Besides physiologic cell death which is referred to as apoptosis, they also exhibit what is known as senescence. The ends of eukaryotic chromosome contain a repetitive sequence of gene code - GGGTTA that are constantly replicated per cell cycle. This sequence of DNA code is called telomere and they mainly serve to protect the ends of the chromosomes so that they do not get tangled. You might want to ask, what do they have to do with aging.
Telomere are replicated by the enzyme known as the telomerase after every cell division. However, per mitotic cell division, the telomere is gradually lost and shortened. As this continues, it gets up to a point where they are now too short for replication and as a result of this, it signals the cells that they are getting old and hence time for them to retire. At this point, the cells stop dividing and subsequently goes into a state of inactivity known as senescence. Once senescence is reached, the cells either remains inactivates and stops dividing or undergo programmed cell death.
The end replication problem causes telomeres to shorten over successive cell divisions
However, not all cells go into a senescence stage. Some type of stem cells, and to be specific, the embryonic stem cells do not go into senescence. Embryonic stem cells are totipotent in nature (cells that can form all types of tissues in the body) hence, they are immortal. This particular feature of immortality is necessary for procreation and life continuity.
Because of this immortality, they embryonic stem cells do not loose their telomerase function unlike as seen in somatic cells. This feature is also seen in cancer cells. When somatic cells bypass senescence, and are unable to stop dividing as at when due, the resulting effect is cancer. Cancerous cells do not respond to cellular signals in cell division which control physiological processes.
For this main reason, cancer cells continue to divide infinitely while at the same time competing for nutrients with normal healthy cells. So, senescence in somatic cells and stems with the exception of embryonic stem cells is a very control system to limit cells that are aged. Summarily, we age due to decline in cell functions caused to either diseases or physiological processes that see preprogrammed already in the cell.
Our life style e.g. smoking, consumption of foods with high radicals can trigger an increase in oxidants that damage healthy cells. Now what if we can reverse this aging in humans, and if we can, is it of benefit to us or not? I will allow you ponder while I explain age reversal.
Age reversal, really worth it?
Reversing age is just like turning back the hands of time, and this begs the question, why should we do it. Well If you take s deep look at the idea of age reversal, to some extent, it has it merit, however still has demerits. The main consideration here would now be, does the benefits outweigh the risk or negative sides of it? Imagine a would full of immortal beings, you grow but you never die. I only wonder how such a world would look like. Just as we have earlier elucidated, some cells need to continuously replicate indefinitely while some need to replicate and at some point stop.
The continuous replication which is typical of healthy embryonic stem cells ensures propagation while somatic cells (non gamete cells that form the body of organisms) which of course are differentiated (have specific functions) cannot replicate indefinitely. Somatic cells which form cells of the tissues like the skin, muscles etc. are well differentiated and have specific functions. Research has shown the possibility of reprogramming a somatic cell and converting it from being a differentiated to an undifferentiated cells like the stem cells. Now this is where the concept of cells reprogramming takes its pride.
I will not go into the intricacies of hoe this is done, I will talk about it in details in another separate post. I just want to introduce you to the possibility that lies in cell reprogramming and possible merits and demerits this procedure could have both on the economy and on we humans in general. In a broad sense of it, cell reprogramming means the engineering or reprogramming of a cell and changing it from its natural form to another form. When we for example convert a cell that is not designed by nature to divide indefinitely like a stem cell and make it do so, this is is simply referred to as pluripotency induction.
Cell reprogramming actually falls under Cell engineering as a branch of biotechnology. The prospect that this field holds so far is incredible because it is now very clear that we can reverse and recreate a lot of tissues or aging or diseased cells. Those things that were thought impossible are now the possible. Through cell reprogramming, we can now comfortably produce a lot of vital tissues, e.g. the laboratory production of blood for use in patients with rare incompatibly disorders. I will discuss this also in details later in separate article.
When cells are reprogrammed i.e. the conversion of adult skin cells (somatic cell) into induced pluripotent stem cells (iPSCs), which have the ability to differentiate into many different types of cells, they take on the characteristics of natural stem cells. The concept has so far helped us understand the real basis of aging, besides other theories that have been proposed to be causes of cell aging. One of the major benefits this concept has provided us as humans, is the new source of using cells for cell-based therapies. In a broader sense of it, it tends to provide us new insights in the field of rejuvenation and regenerative medicine.
The production of cellular therapies requires the optimization of four steps: first, isolating and culturing cells that can be readily obtained from a patient in a non-invasive fashion. Second, the reprogramming of these cells into a pluripotent state. Third, the directed differentiation of those patient-specific pluripotent cells into the cell type relevant to their disease. And, fourth, techniques for repairing any intrinsic disease-causing genetic defects and transplantation of the repaired, differentiated cells into the patient. Notably, these disease-relevant patient cells can also be used for in vitro disease modeling which may yield new insights into disease mechanisms and drug discovery
When the main aim of age reversal is mainly channeled to healing, tissue repair, treatment of life threatening diseases like cancers, then I sure would not have any problem welcoming the idea. But when it directed to reversing natural aging cells or more like for example, reversing age in humans, then I would not welcome the idea. I mean, who actually wants to live forever in life, I don't think anyone does. We all as humans have natural saturation point. No matter how interesting life might be, one day will come and we will all wish to rest. This is inherent in us as humans.
The research work done and published by David Sinclair and his research team showed the possibility of age reversal, though this was done in rats and not in humans. From their research findings, they concluded that epigenetic changes (changes that occurs in DNA but do not alter the gene code, e.g. DNA methylation, Histone Modifications etc.) are the driving factors for aging in cells.
So if they can reverse these changes by rebooting the cells, then factors that drive aging process will be suppressed and as a result reversed. If this is replicated in humans and possibly successful, then indeed, we could all have a brighter hope for tomorrow as regards to treatment of chronic diseases of the brain, heart etc. However, I still have my doubts on the feasibility of this in humans and the possible consequences this would have should it be extended to actual age reversal in humans and not just treatment of chronic diseases. This is more like playing god. I don't want to live forever on this planet earth, and never will I wish for it.
If all the ancestors that have lived before us were still alive, how would the world look like? One thing is sure to happen - over population and increased human pressure on the environment and the ecosystem system at large. The pursuit will be worth it, if it is mainly channeled to finding the permanent cure to neurodegenerative diseases which usually are known to have no cure. If the brain cells, hearts cells for example can be reprogrammed and induced to regenerate new neurons and cardiomyocytes respectively, then, our older ones who are prone to this old age disease can comfortably live their life until the right time for them to pass on is reached.
I think more focus should be on the regenerative potential of the approach and not channeling resources to actual age reversal in humans. It is not worth it in this regard. Regenerative medicine is indeed a beautiful area worth exploring because the prospect it has is limitless, however, I do not buy the idea of playing god by actually making attempts to actually reverse human age. This to me does not look ethical and for sure would have measurable consequences. Cloning of humans was resisted, this will likely not be an exception. Its application on treatment of chronic diseases, yes! Reversing our age, No!
Teach more ways to live right, that I may increase my life span and die a natural death at the appointed time. Death is inevitable in all humans, no matter how try to stop it. The best we can do for ourselves stay healthy by maintaining healthy life style and eating healthy foods.
Alright, that will be all for today, hopefully when I have time, I will discus with you in practical ways how this pluripotency induction is carried out. See ya!
References
•Scientists Have Reached a Key Milestone in Learning How to Reverse Aging
•Loss of epigenetic information as a cause of mammalian aging
•Scientists' enthusiasm grows for induced pluripotent cells
•Human age reversal: Fact or fiction?
•Cellular reprogramming and epigenetic rejuvenation
•Epigenetic reprogramming of cell identity: lessons from development for regenerative medicine