Many of you have written to me, expressing surprise about the lack of public reaction (such as media interest) regarding the potential for telomerase therapy to treat age-related diseases. Some of you wonder why people (and particularly the media) “don’t get it”. I’ve had the same thought for a bit more than two decades now, […]
Many of you have written to me, expressing surprise about the lack of public reaction (such as media interest) regarding the potential for telomerase therapy to treat age-related diseases. Some of you wonder why people (and particularly the media) “don’t get it”. I’ve had the same thought for a bit more than two decades now, since I published the first book and the first articles on the potential of telomerase therapy. The lack of understanding applies not only to the media, which is neither critical nor surprising, but to many in the investment community and to the pharmacology industry, which is critical if we are to save human lives.
The major reason for that lack of understanding is human nature. Most people have a firmly-held misconception about how aging works and never realize the error. Without thinking about it (which is the fundamental problem), most people think of aging as entropy. In reality, aging is a lot more complicated (as are most things). Aging isn’t the same as entropy; aging is the gradual inability of cell maintenance to keep up with entropy, which is a very different kettle of fish. Aging hinges on the balance between entropy and maintenance. If you think about it, that’s really what biology is all about: maintaining a extremely complex system in the face of entropy. Life is resistance to entropy. Life is continually building, recycling, and maintaining a complex system, that is continually coming apart, thanks to entropy. This is a balance that works quite well generally, which is why life still continues quite splendidly on this planet, a good three and a half billion years after it began. Who says you can’t resist entropy indefinitely?
Nor is aging universal, just because we see it in ourselves, our pets, and the animals we raise. In some organisms (some multi-cellular and some unicellular), aging never occurs. In other organisms (again, some multi-cellular and some unicellular), aging occurs quite predictably as maintenance slows down, allowing entropy to have its way as the organism ages, fails, and dies. While aging is a lot more than just entropy, most people never even begin to consider the facts and sail along with the unexamined assumption that “aging is entropy”.
It’s not that simple. It never is.
Nor are telomeres the “cause” of aging. Telomeres don’t cause aging, they are just one (very important) part of an enormously complicated cascade of processes that result in age-related pathology and aging itself. Telomeres are important only because they play a key role at the crossroads of this cascade of pathology. Being at the crossroads, telomeres represent the single most effective point of intervention, both clinically and financially. They are the only place that we can entirely reset the gradually deceleration in cell maintenance with a single intervention and it’s the only place that we can leverage our interventions into a strikingly lower cost of health care. Better care, for less cost.
The other problem that keeps people from appreciating the potential of telomerase therapy is inertia, or perhaps inertia and the fear of undermining their own careers. It’s not merely the inertia of never examining our assumptions, but the professional inertia that occurs when we suspect that – should we examine those assumptions – our entire professional lifetime of work may have been not only misdirected, but be seen as valueless, a truly frightening thought and an understandable fear. Human nature being what it is, the result is a stolid inertia from professionals who have spent many decades pursuing a faulty (and incomplete) model of aging and age-related disease. If any of us had spent 40 years of our professional life working for certain global pharmaceutical firms, for example, we would be loathe to give up the assumption that beta amyloid causes Alzheimer’s disease. After all, that model (despite lacking any support) has been the central focus, the raison-d’etre, for everything we have done professionally for several decades. Would any of us be willing to look clearly at reality, knowing that an honest, thoughtful, and careful appraisal of reality might suggest we had wasted those years, along with our personal efforts and dedication? It is asking too much of human nature. In a corporate, rather than a personal sense, this is equally true of drug companies that have invested hundreds of millions of dollars in what has now been proven to be a fruitless endeavor. The endeavor has been aimed at the wrong target, but it’s a lot of years, a lot of money, and a lot of effort, making it difficult to be honest about the prospects, let alone willing to go back to square one and ask if our assumptions were wrong in the first place. Old adages notwithstanding, people and institutions really do “throw good money after bad” and we do it both with a will and stunning consistency.
Yet, there is reason for a realistic optimism. Over the past two decades, there are a growing number of people who look at the data, reexamine their assumptions, and develop a close relationship with the reality of how aging works. That number continues to escalate, and the time when we can take telomerase therapy to an effective clinical trial continues to shrink. We see resources and commitment moving steadily toward a more sophisticated understanding of both Alzheimer’s disease and aging itself. The combination of resources and commitment will soon bring us to a new ability to treat diseases that, until now, have been beyond our understanding, let alone beyond our help.
We have the compassion to save lives; we will soon have the ability.
An optimistic message for 2018 – thank you!
Optimistic perhaps, but realistic as well.
Hello, Dr. Fossel
I find your theory of telomeres very convincing. I’ve read The Telomerase Revolution and found your scientific view about how the aging process”begins”, quiet plausible and satisfying. I’ve also read Aubrey’s De Grey book and I think your theory to be both easier to implement and probably much more effective.
The only idea from Aubrey’s that I think would be wise to incorporate into your endeavor at proving that your theory is right is to first apply thorough and complete telomeres restoration to mice in order to prove to the world that true age reversal is feasible to accomplish in normally aging, complex organisms. What Aubrey deems “Robust Mouse Age Reversal”.
Thank you Guido. As you may know, we already have proof of our ability to reverse aging in human cells and human tissues (now almost two decades ago), and a growing body of data on age-reversal in mice. The prospect of reversing aging in all cells of an adult animal (or human) is replete with technical issues, but is quite feasible. At the moment, and for strategic reasons, we are approaching the issue via Alzheimer’s disease. AD has the advantage of being the “high-hanging fruit”. Proof that we can reverse the cognitive decline in AD will make our point forcefully. We are, however, simultaneously moving ahead on the techniques required for full-body age reversal, particularly as measured not only by biomarkers, but by age-related disease. In short, I agree with you completely and we’ll get there as soon as we have sufficient funding to do so.
One thing I’ve always wondered about Michael- granted shortening telomeres result in altered gene expression that is detrimental to the cell’s maintenance, but what about altered gene expression due to general epigenetic aging unrelated to telomere length, such as described by the Horvath Clock? I’ve never seen any data to show that such changes are important, but I wondered if you had a take on it?
Thanks in advance,
The evidence suggests that “general epigenetic aging” IS related to telomere length. While there are exceptions, such as 1) tissue-specific epigenetic markers, 2) the epigenetic changes that occur with pre-adult and pubertal development, and 3) environmental influenced changes in gene expression, all of the epigenetic changes that we see as related to aging are likely to be modulated by telomere shortening and (as a general rule) reversible by telomere lengthening.
Hello Dr. Fossel,
I feel privileged to have been able to see the interview you did with Peggy Sarlin, on her series of, Regain your Brain. I am a 62 year old woman, who had to retire at age 57, because of age related memory problems. I sustained a closed head TBI, at the age of 27,due to a MVA, and some of it is related to that.
I am frustrated at the lack of information main stream medicine has been able to give me, and for that matter the ” throwing up of the hands, ” if you will, at what can be done to help.Any information I have gotten, has been through my own diligent efforts in finding some answers.
Thank you for what you’re saying and doing, and if you need volunteers for your research, don’t hesitate to contact me.