Aubrey de Grey is a biomedical gerontologist based in Cambridge, England. He is editor-in-chief of the academic journal Rejuvenation Research, author of The Mitochondrial Free Radical Theory of Aging (1999) and co-author of Ending Aging (2007).
As Chief Science Officer of the SENS Foundation, Aubrey has been interviewed by numerous media sources in the US and Europe, including an in-depth 60 Minutes report titled “The Quest for Immortality.”
Aubrey’s research focuses on whether regenerative medicine can thwart the aging process. He works on the development of what he calls “Strategies for Engineered Negligible Senescence” (SENS), a tissue-repair initiative intended to rejuvenate the human body and allow an indefinite life span. To this end, he has identified seven types of molecular and cellular damage caused by normal metabolic processes. Aubrey’s focus is to perfect therapies to repair this damage.
We asked Aubrey to write a concise summary of where the SENS Foundation’s research stands now and why more resources are not being allocated to eradicating aging.
|Aubrey de Grey, PhD|
Historically, the tacit goal of those who dare to dream of postponing age-related ill health has been to apply some kind of intervention to retard pathogenic aging processes. The thinking has been:
- we don’t understand aging very well at all,
- however, we see a huge variation in rates of aging in nature, both between species and in response to environmental cues (notably calorie restriction),
- thus, maybe we can emulate/extrapolate from these differences to slow human aging, even though we don’t understand the details.
However, it has proven challenging up until now to execute this plan.
In the past decade, a radically different approach to intervening in aging has emerged. It took a few years to gain credence within the biogerontology community, and there remain some old guard who resist engaging in debate on this topic. Fortunately, the army of prestigious academics who enthusiastically endorse this new approach, at least as a viable alternative to prior ideas, has grown to a point where it is unrealistic to reject it out of hand. This approach is the application of regenerative medicine to aging.
Regenerative medicine is the process of creating living, functional tissues to repair or replace cellular function lost due to damage, including injuries sustained as a consequence of aging. Regenerative medicine refers to clinical therapies that may involve the injection of stem cells or progenitor cells; the induction of removal of damaged molecules or cells by biologically active molecules; and transplantation of in vitro grown organs and tissues, all with the goal of restoring the structure of aged tissue to its state in young adulthood. This field holds the promise of regenerating damaged tissues in the body by stimulating previously irreparable organs to heal themselves. SENS Foundation is focused on pursuing this approach, especially by sponsoring the early stage, proof-of-concept research that is required in some areas that are still being neglected by other funding bodies. Details can be found in my academic publications (especially between 2002 and 2007) at www.sens.org and in my book Ending Aging (St. Martin’s Press, 2007).
Since aging is indisputably humanity’s worst medical problem, with the treatment (albeit only minimally effective) of age-related diseases consuming the vast majority of the industrialized world’s medical budget, one would imagine that all reasonable approaches to the development of medicine to postpone it would be vigorously pursued and well funded. Unfortunately, none of them are. Neither the retardation of aging nor its repair receives a fraction of the research budget—whether from the public purse or from the for-profit biotech sector—that is enjoyed by disease-specific research. And this is despite the fact that gerontologists have been pointing out for decades that even modest progress in the implementation of “preventative geriatrics”—which is exactly what treatment for aging would be—would be staggeringly cost-effective.
Why so little money is being allocated
I believe that the overwhelming reason why politicians (and, to a lesser extent, companies) have not heard this message is not because they fail to understand it but because they dispute the premise. There is a profoundly deep-seated belief that aging is untreatable. This has been reinforced, I am afraid to say, by the short-sighted protestations of past gerontologists who mistakenly claimed “aging is not a disease.” These grossly inaccurate proclamations also reinforce their audience’s tragic misconception as to whether aging is in fact a bad thing at all!
Thus, as long as mainstream gerontologists can point only to very flimsy evidence that anything substantive could be expected to emerge from their efforts even if greatly increased funding were forthcoming, they will fail to provide a convincing argument that vastly greater sums of resources should be allocated to this critical arena of medical research. It doesn’t matter how good a case we make that astronomically many dollars will be saved by progress against aging at a relatively small cost in the funding of the necessary research. As long as the holders of purse strings continue to believe that there is no chance whatsoever of research delivering progress against aging, they will conclude that such research is quixotic, so the necessary resources will not be mobilized.
This brings me to the first opportunity that arises from the new paradigm of applying regenerative medicine to aging. Regenerative medicine has not enjoyed a precisely smooth progression from concept to clinic over the years, but today it is riding high. Breakthroughs in stem cell research (most notably the “induced pluripotent stem cell” approach to the immune rejection problem) and in tissue engineering (most notably the decellularization approach to the vascularization problem) has propelled regenerative medicine to an enviable stature within biology and biotechnology, among both the scientific community and the general public. Most importantly, this stature exists in terms of the approach’s perceived feasibility, not merely its theoretical attractiveness. Accordingly, to the extent that its applicability to aging is accepted, regenerative medicine has the potential to transcend the entrenched fatalism that I have noted above.
Will translational gerontology be accepted by aging researchers?
It remains, therefore, to examine the question of whether the applicability of regenerative medicine to aging will be accepted. The effort to elevate it to that status is, I must concede, a work in progress. The core difficulty is that, in order to appreciate the feasibility of repairing the molecular and cellular damage of aging, one must acquire an in-depth grasp of two fields that have historically communicated hardly at all.
Regenerative medicine has overwhelmingly been developed with a view to treating acute injury, so very few of its practitioners are up to speed on the current status of biogerontology. Conversely, the focus of biogerontology on comparative analysis, with the aim of eventually developing interventions that slow aging rather than repairing it, has not induced biogerontologists to maintain a thorough understanding of the rate of progress in regenerative medicine.
Inevitably, this lack of mutual education between the two fields has resulted in a high degree of over-pessimism about each other’s work: being out-of-date about a field equates inexorably to presuming that it is less far advanced than it actually is. My own work over the past several years has, accordingly, incorporated a sustained effort to bring these communities together and facilitate that mutual education.
Unfortunately, there is an extremely powerful force opposing this ostensibly uncontroversial effort: funding. As science funding has fallen further and further short of demand, and investigators have been forced to spend ever more of their time applying for grants and publishing as much as possible to increase their chances of said funding, it has become progressively less possible to pursue interdisciplinary work, and more imperative to “stick to what one knows” and get money in the door by playing to one’s established strengths. This is immensely bad for science in general, as is probably obvious to readers. But it is particularly bad in the case of biogerontology.
This is because, among scientific disciplines, biogerontology has a very—in fact, arguably a uniquely—high profile in the mainstream media. The problem is that the “newcomer” nature of regenerative medicine on the biomedical gerontology playing field translates into considerable unfamiliarity with its relevance to aging on the part of journalists. It remains the unfortunate case that when a reporter reaches for his or her phone book in relation to some new breakthrough concerning aging, the recipients of the calls are overwhelmingly those who represent the old-school, “retardation” approach to combating aging. This might not be so problematic if scientists were mainly minded to highlight the importance of diversity in approaching any research area, but the funding-fuelled tyranny described above decisively prevents such altruism. The result is that the public, policy-makers, and most of the scientific community are maintained in a state of wholly inadequate information on this topic.
The benefit to those who are already able to help
Biogerontology is not your average scientific discipline. It is the study of a phenomenon that currently accounts for two-thirds of all deaths worldwide, and 90% of all deaths within the industrialized world. If measured in terms of suffering or of health care costs, the numbers are equally staggering.
As several of my colleagues have noted over many decades, and with increasing energy since the turn of the millennium, the impact of even a modest degree of progress in postponing age-related diseases, as a result of intervening in their common cause (aging), would be immense. The missing link, as already discussed, is the view of policy-makers as to whether there is any chance of success. This could be changed if those to whom policy-makers look for guidance were to alert them to the potential for regenerative medicine to postpone aging, but, as I have also discussed above, the funding environment within which the acknowledged experts of biogerontology are forced to work impels them to ignore that option, whether in their own work or in their pronouncements to others, in favor of the far less promising alternatives that they have pursued in years past.
So why is everyone still oblivious to this disaster? Ultimately, I believe that the answer comes down to just one thing: a failure to appreciate who can potentially benefit from progress. The massive Achilles’ heel of biomedical gerontology in terms of appeal to the wider world has always been its focus on lifelong interventions. Those in a position to influence the level of financial support for such work, therefore, are required to start from a position of disenfranchised altruism (since they are already too old to benefit from therapies that need to be begun in youth or earlier). That is a noble position, to be sure, but realistically it is not one that enjoys prolific favor from the public. In particular, it is not a promising target for philanthropy.
But the regenerative approach changes all that—indeed, it abolishes it. The whole point of all regenerative medicine is to start with people who are already carrying a significant quantity of damage, which the intervention will then repair. As such, if it can be made to work, rejuvenation biotechnology has the capacity to deliver the substantial (exactly how substantial remains to be seen, but we won’t know until we try) postponement of all the debilities that we most fear as we progress toward the age at which we expect our health to fail. And it can deliver it to people who are already in middle age or older by the time the therapies materialize.
Turning research into reality
So, well, can it be made to work? There are two ways for those with the financial resources (i.e., today’s ultra-wealthy) to answer that question. One way is to accept the prognostications of those who occupy positions of prestige among the established biogerontology community, who still know and understand little of regenerative medicine, and who, with varying degrees of stridency, declare that aging is practically beyond the reach of medicine and that all we can realistically seek to do is understand aging well enough to postpone the ill-health of old age by a few years.
The other way is to enlighten those with financial resources to the burgeoning field of regenerative medicine and the ever-increasing plethora of distinguished leaders of that field who are lining up behind the proposition that aging can be reversed by the comprehensive repair of the molecular and cellular damage that underlies it.
If these individuals want to avoid the ill health of old age, now is their chance to take meaningful action. We still need as much knowledge as we can get about how aging really works. But augment it with a similar level of support for unashamedly translational biogerontology, focused on the postponement of age-related ill health, and focused especially on interventions that will benefit those who are already adversely impacted by aging, and the result will be the saving of hundreds of millions of lives, along with countless life-years of suffering.
We are all in the same lifeboat. The difference is that some have available financial resources that could result in their own rescue from the horrific consequences of aging, along with all of mankind. I urge those fortunate enough to have accumulated wealth beyond their worldly needs to emulate what Larry Ellison has done, i.e., support scientists who are aggressively researching means to gain control over aging. It seems so logical, yet Larry Ellison is among only a few who has demonstrated the clear vision to fund those who could enable humans to rapidly evolve into a species that enjoys an indefinitely extended healthy life span.
The next section of this article describes Larry Ellison’s unique approach to funding aging research. I urge Larry and others to consider augmenting their translational biogerontology arena, and particularly to the regenerative medicine approach.