Today, February 21, was the birthday of Jeanne Louise Calment – the oldest confirmed living human being, who lived for an amazing 122 years and 164 days!
Just imagine all the history she had seen, how much the world changed during her lifetime, and all the knowledge and wisdom she had gained. What if advances in science and technology could have kept her healthy and youthful and she was still with us?
How might rejuvenation biotechnology have helped Jeanne?
So, for a bit of fun, let’s have a look at how some of the technologies currently in development might have helped her to continue enjoying a healthy and independent life.
Where would we begin her health management if the technologies available to mice were successfully translated to humans? It would make sense, to begin with the critical weaknesses, so let’s find out what they were in the case of Jeanne.
The cause of her death was not specified, and in most cases, this means that it was caused by heart failure. This is particularly likely because, after her hip fracture, Jeanne was not as active as before, which may have led to the deterioration of her cardiovascular system. Indeed, her doctors did record a moderate heart failure a few years before her death.
Apart from that, Jeanne suffered from a chronic cough and rheumatism, and in her later years, she was almost blind and deaf. However, tests did not show any signs of dementia. Her hip fracture was not the only trauma she survived; in fact, she broke her leg and elbow before her hip, which is often a sign of both sarcopenia (muscle atrophy) and osteoporosis.
We also know that she survived an episode of severe flu, so we can presume that, despite her age, her immune system was still reasonably strong.
Her heart condition was clearly her main risk, so this is where we would begin. There a number of therapies in development to combat heart disease and failure and to restore cardiovascular health. Heart disease is the primary cause of death worldwide, so the race is on to develop effective ways of treating and reversing it.
One area of research that has shown promise involves modulating the immune system to reduce the accumulation of plaques in the arteries. Atherosclerosis is an age-related disease in which toxic, oxidized cholesterol deposits in the bloodstream cause inflammation in the arterial walls. This causes macrophages to swarm to these deposits and try to clean them up.
Unfortunately, macrophages are not as robust as we might like, and over time, they ingest so much waste that they either die outright or become senescent and become dysfunctional foam cells, which send out inflammatory signals that further drive the aging process. This inflammation then brings in more macrophages, which also succumb to the same fate over time.
Macrophages are a fundamental reason for the increasing formation of arterial plaques, which gradually close off the blood supply and can lead to strokes and heart attacks when pieces of plaque break off and block the blood flow.
Research into changing the behavior of macrophages is showing promise for treating heart disease. Essentially, macrophages can be of either the M1 inflammatory or the M2 healing type, depending on the signals they encounter at injury sites, including plaques. Research is now focusing on encouraging macrophages to favor the M2 type, thus reducing inflammation and causing fewer macrophages to swarm to plaques and become foam cells.
There are other, more robust, approaches in development that aim to completely remove plaques by breaking them down directly. Plaques could also potentially be removed by using specialized antibodies that home in on them and remove them from the tissue as part of a passive or active vaccination approach.
It is well documented that physical activity is crucial in maintaining health in our later years, which is why the next step would involve treating Jeanne to regain her muscle mass and bone density, thus avoiding the risk of more falls and traumas. Again, this is speculation, but deactivating the myostatin gene through gene therapy is one possible approach.
Another mandatory element would be a course of physical rehabilitation. In addition to these measures, vitamin D3 and vitamin K2 (MK7) could be prescribed to decrease osteoporosis.
This is where rheumatism could be an obstacle. As we know, the deterioration of joints and the spine is at least partially the result of chronic inflammation provoked by senescent cell accumulation. Therefore, the next technology that could have potentially helped is senolytics.
Senolytics are a new class of drugs that remove non-dividing, pro-inflammatory senescent cells from the body. As we age, we accumulate more and more of these cells, which impair tissue repair and regeneration, and removing them has been shown to improve tissue health in rodent studies. Senolytics work by encouraging senescent cells to enter a self-destruct program known as apoptosis and a number of these drugs are poised to enter human trials in the near future.
However, the deterioration of joints is also partly due to stem cell depletion, and so stem cell therapies to increase cartilage tissue would also be potential co-therapies with senolytics. Recent human clinical trials have shown dramatic improvement in reducing frailty in older people and would seem to be an ideal way to help restore mobility and balance.
What could the outcome of these treatments be?
They would possibly decrease the risk of death in subsequent months, allowing time for further interventions. At this point, Jeanne would likely regain her mobility after having her muscle capacity and joints restored. She could have a more active lifestyle, which would help regulate her metabolism.
Improving quality of life
At this point, Jeanne would still remain dependent because of her impaired vision. Age-related blindness has multiple potential causes, including age-related macular degeneration (AMD) and cataracts.
In the case of AMD, Ichor Therapeutics is working on its Lysoclear system, which destroys the toxic vitamin A aggregate A2E, which likely contributes to this disease.
For cataracts, there is always the current surgical option, though Jeanne did not get this due to her heart issues. If regenerative therapies had restored her heart, she could have undergone this routine surgery and received artificial crystalline lenses in both eyes.
The next problem to consider would be her cough; this was likely the consequence of smoking, a habit that is extremely harmful to health and drives a number of aging processes, including DNA damage, epigenetic changes, and cellular senescence. If you are looking to age yourself as quickly as possible, then smoking would be the ideal approach; needless to say, we do not recommend it.
Like many older people who smoke, it is likely that she may have had some pulmonary fibrosis; if this was the case, then a therapy that addresses the fibrotic tissue would be in order. Thankfully, recent advances from Dr. Maria Blasco at the CNIO in Madrid have shown a potential way of reversing fibrosis via telomerase gene therapy.
Telomeres are the protective caps on the ends of our chromosomes, and they grow shorter each time a cell divides; when these caps become critically short, the cell no longer divides and becomes senescent. However, in the case of fibrosis, the rate of erosion of telomeres is much faster, and the tissue becomes scarred and fibrotic.
Telomerase gene therapy has been tested in a brand-new fibrosis mouse model and is demonstrated to reverse the condition within a matter of weeks. The next step for the CNIO is to translate this to humans and begin human trials; given that there is no current cure for pulmonary fibrosis, a positive result would be a game changer.
In addition to these measures, we could safeguard Jeanne’s future further if we could strengthen her immune system. Our immune systems are responsible for keeping the number of cancer cells low, and a recent study suggests that their healthy operation is even more important in cancer risk than DNA damage is. If this is the case, and there is much reason to believe it may be so, then keeping her immune system working properly would be the key to continued health.
The thymus is the most important place to begin, as of all our immune organs, this is the one that shrinks as we age, turning from healthy immune cell-producing tissue to fat. Without a thymus, there are very few T cells being produced, and this leaves us wide open to cancer, microbial invaders, and pathogens. A number of groups are working on solutions to restore the thymus, including Dr. Greg Fahy, who has already enjoyed some success in human trials.
Combining all of these therapies could possibly lead to a significant improvement in health. We don’t know yet if these systemic therapies will help old people start looking younger, but we can speculate that Jeanne might regain her hair, and it might even become darker.
There may also be some potential improvement of skin, given that senescent cells inhibit tissue repair and regeneration as well as wound healing. This could mean looking younger again once some age-related damage is repaired.
There are of course other things that would need to be addressed, as aging is comprised of a number of different processes. The next problems to address would depend greatly on the outcome of the initial approaches discussed above.
It is most important to us that, at this point, Jeanne would be feeling good enough to restart her social life (which was abandoned in the last months of her life because of deteriorating health) and maybe even find a hobby or some sort of social work to do.
After all, if you have your health, then the door is open to a more active life that is worth living and filled with possibilities.
Health and long life
We often think of the older generations during my work and hope that we can save them or, more accurately, give them the choice to live longer and stay healthy. Every time someone passes away, we lose another piece of history, and it makes our work ever more urgent.
Jeanne lived an independent life for the majority of her years; it was only at the age of 110, following a fire in her apartment, that she went to live in a nursing home. Even when in the nursing home, she remained mostly independent and was able to care for herself.
She certainly set a record, changing our ideas about maximum human lifespan and causing many people to adjust their expectations about what is possible. However, the downside is that many people associate long life with decrepitude and age-related ill health.
The good news is that science is working to offer you a healthier and longer life rather than keeping you alive but in poor health, as you age, the way current medicine often does. Some people suggest that we must choose between long lives and good health, but there is every chance that we can have both thanks to the advances in aging research.
Numerous experiments in animals have shown that addressing the underlying processes of aging in young and middle-aged animals can help them maintain their health and stay active for longer; the next step is translating these results into clinical practice for humans. When this happens, chronological age will no longer be closely related to biological age.
Forget mantras like “It is not the years in your life but the life in your years that counts”; these are the words of people who had no choice and were forced to accept aging because the technology was not in place to do something about it. We now live in an era when we are within striking distance of being able to intervene against the aging processes themselves in order to prevent or reverse age-related diseases.
Jeanne used to say: “I have only one wrinkle… and I’m sitting on it”. She was a strong, independent woman who had a great sense of humor, and a thirst for life. We often wonder if she would still be with us if she had been given the choice to remain healthy and continue to enjoy life.
We cannot know what she would have chosen, but we honestly believe that she would.