Slowing Down or Reversing the Aging Process:
Stephen L. DeFelice, M.D.
The Rationale and Clinical Approach
It is now possible to make dramatic progress in altering the
aging process. Convincing clinical and laboratory studies indicate that:
the aging process in humans and animals can be either slowed down or
reversed; partial starvation has prolonged the lives of experimental
animals; a combination of l-acetylcarnitine and alpha lipoic acid
reverted very old rats to middle-age status; the use of growth hormones
has reversed the fat/muscle ratio in elderly humans with ratios
returning to levels found in younger people.
Other substances have also been clinically shown to reverse some
aspects of aging. Yet the historic lack of interest in pursuing research
on the aging process persists by all major parties in the
medical-scientific community. It is no longer a question of whether or
not aging can be reversed. The question we need to ask ourselves is,
"Why aren't we doing as much as we can in this area?"
The solution? Two steps must be taken before the anti-aging journey
begins. First, there must be a national awareness of the nature of the
anti-aging effort and what must be done. Second, we must be willing to
modify the cultural values and regulatory policies that now prevent us
from accomplishing this objective.
This is a complex matter. Let's take a look at some of the issues involved in our present situation.
Aging as a Disease Process
It is time that modern medicine accepted the concept that aging is an
ongoing disease process with a one hundred percent mortality. Aging
leads to multiple body organ and systemic failure, ranging from heart
disease and Alzheimer's to an impaired immune system that can lead to
various types of cancer and infections.
Whether anyone actually dies of the disease "Old Age" has not yet
been determined. Why? For the simple reason that "old age" has not been
scientifically defined. Despite the lack of a precise definition, old
age can be clinically determined simply by observing an aging person's
inexorable loss of energy and shrinking body mass.
It has always been assumed that aging is a natural, inevitable
process that could not and should not be tampered with. "It's natural
and not a disease," goes the saying, "and it cannot be treated." Some
even believe that it is morally wrong to do soóand their numbers are not
few. This worldwide cultural mindset has long been, and continues to
be, the major culprit blocking any national anti-aging initiative.
Fortunately, within the past decade or so, U. S. physicians and
scientists are beginning to open up their minds based on the
aforementioned and other studies. Conceptually, the aging process now
can be considered as a multi-factorial process with many abnormal events
going on. Aging, by the way, is conceptually similar to the growth of
an infant. As with aging, infant development is a multi-factorial
process in which many biologic systems are involved.
Aging and Genes
Though it may be wishful thinking, there could exist either a single
anti-aging or aging-gene. Medical science could discover ways to
influence them medically to retard or turn back the hands of time. On
the assumption that one or both such genes exist, it would still take a
very long time to find and prove that either gene can be manipulated in a
manner that will prolong human life. In our present system, it would
take decades to do the clinical studies required to finally obtain FDA
Because it seems logical to conclude that aging is multi-factorial,
it is then equally logical to believe that the attack against aging
should also be multi-factorial. A multi-factorial combination of medical
weaponósuch as pharmaceuticals, nutraceuticals (e.g., dietary
supplements or fortified foods), medical devices, transplantation and
other weapons could prevent or correct the physical processes that are
taking us prematurely to the "Beyond".
Unfortunately, in modern academic and powerful government circles,
the concept of using mixtures continues to have an image of "guru- ism"
and illegitimacy. The complex origins of this prejudice lie in the
cultural-regulatory dynamics of the mid-twentieth century. For these
reasons, the use of combination therapies to attack disease, let alone
aging, has been effectively blocked.
However, we seemed to have forgotten or ignore the fact that children
grow and maintain their health by eating a meal, the most miraculous
nutraceutical combination in the world. Good meals keep us alive and
fuel the multi-factorial process of healthy physical and mental growth.
Of course, in addition to nutraceutical combinations, children also need
vaccines, antibiotics, surgery and other treatments to maintain their
healthy growth all of which, in a real sense, are part of the combined
and broad medical therapy. And what doctors do not employ multiple modes
of therapy in their patients?
The Inhibiting Impact of FDA Policies
The FDA has a policy that each single medical weapon, and all
possible combinations of total combination treatments, must be
individually tested and compared. This is simply absurd. If one were to
study all of the ingredients of all possible combinations of a
20-product anti-aging formula, according to current FDA guidelines, it
would require 1.23 to the 20th power! If a study had 1,000 patients in
each group (a small number for such a study), and the cost was $10,000
per patient, then we can add another seven zeros to this figure. What
would the cost then be? A sum greater than the gross national product of
the entire world. This is clearly untenable. This fact is also a major
reason why we need "Doctornauts." (See DeFelice Commentary:
This one FDA policy alone is a huge barrier to encouraging anti-aging
clinical research and must be changed. Such approval should simply be
based on the risk/benefit ratio of the total combination approach. If
the total beneficial effect of the combination exceeds the bad effects,
then this should be the definition of the FDA standard of approval. But
FDA does not see it this way and neither does the academic medical
The Role of Patents
There is also another powerful, related negative factorópatents! The
pharmaceutical industry understandably attempts to discover strongly
patented substances in order to obtain sufficient product exclusivity in
order to justify the enormous costs to obtain FDA approval for a drug.
It would be economic suicide not to do this. Virtually all of the drugs
that are approved are single substances and not combination products.
This is a huge impediment to the development of the multi-factorial
products needed to combat aging as well as disease.
A positive issue related to patents presents itself. If the
combination product is active, either in the laboratory or the clinical
study, a company can, if certain conditions are met, then obtain a
composition patent that sometimes can be sufficiently strong to justify
the financial investment needed for the FDA approval. There are other
patent opportunities as well as problems, but the overall ability to
obtain commercial exclusivity needs to be encouraged.
The Anti-Aging Act
There is an additional way that product exclusivity can be
strengthened. Congress, as it did with the successful Orphan Drug Act,
can pass the Anti-Aging Act which would grant a company a period of
exclusivity to commercialize the combination. Patent or no patent, no
commercial competition would be allowed during this period.
It is extremely important to appreciate that the anti-aging
combination studies will, almost by definition, fall outside FDA
standard clinical guidelines.
The following is an example of one approach under the Anti-Aging Act:
A laboratory would look into human aging cells that are losing their
energy and on their way to cell death (or apoptosis). Researchers would
determine what natural substances are low in concentration. The loss of
energy is the hallmark of aging. Perhaps by clinically administering a
rational medical combination of low-level substances to replenish the
aging cells, the energy of such cells could then be increased. Not only
might this combination increase the energy performance of the already
weakened cells in the heart, brain and other parts of the body, but
also, it might also prolong cellular life span.
In addition, we now know that there are cells in the body that are
dormant with the capacity to be awakened and rejuvenated. Further, there
are adult stem cells that can be stimulated in the laboratory to
produce new youthful cells with specific body functions.
Another conceptual clinical study could evaluate the potential for a
combination of growth factorsósuch as growth hormone, anti-inflammatory
pharmaceuticals and multiple nutraceuticalsóto create normal
energy-producing cells. Periodic intravenous administration of certain
single natural substances contained in the mixture may be required in
order to achieve sufficient blood levels which would permit them to
enter the cells and do their job.
How to Measure Success
What will be our measure, clinically? Unfortunately, it is
impractical to measure whether a particular combination will prolong
human life. This is not yet a generally recognized fact. We must,
instead, rely on surrogate markers or measurements that are considered
to be medically beneficial. An example of a surrogate marker would be
cholesterol. If a substance lowers cholesterol in clinical studies, it
is then presumed to have a beneficial effect (surrogate marker).
However, we cannot be sure that lowering cholesterol levels with this
particular substance prevents heart attacks unless a clinical study is
done. The latter is considered a clinical endpoint. With respect to
aging, the clinical endpoint would be the prolongation of life.
Regarding mental and emotional clinical effects, a general scale of
measurements should be designed to include memory function and feelings
of well-being. Regarding physical measurements, cardiac performance and
general muscle strength, along with the responsiveness of the immune
system, should be evaluated.
Assuming that the combination successfully reverses the aging
process, what would be sufficient evidence for the FDA to permit the
formulation to be made available to physicians in medical practice?
If the results of preliminary clinical studies are encouraging ñwhich
means that the clinical benefit observed exceeds the riskóthen
long-term studies in large numbers of patients should be initiated to
determine if the risk/benefit ratio of the combination is maintained. If
it is maintained, then the product should be made available to
physicians for use in the appropriate populations. However, there is
also an obligation to continue with post-marketing studies for a
specified period of time. If the combination is given to the very old
population, then these post- marketing studies can last for a lifetime.
Specific clinical guidelines for anti-aging combinations are not feasible and should be structured on a case-by-case basis.
What About the Bad Effects?
We must, of course, constantly be on the alert for the adverse
effects or toxicity of any therapy for any condition. They inevitably
occur to one degree or another and, therefore, the volunteer patient
must be closely monitored. But there is an important caveat. We must be
careful not to be in a hurry to attribute such unwanted side effects to
the therapy itself. Many such events can occur in the natural process of
aging itself. Practically all of the aging volunteers will have
accompanying diseases (e.g., depression, memory loss, sexual
dysfunction, arthritis, heart disease, diabetes and cancer). These
conditions will normally worsen with the passing of time.
In our present cultural mentality, if one volunteer should die during
a clinical study, even of natural causes, we can expect to see a
national, media-driven uproar resulting in the cancellation of the study
and probably other similar ongoing ones. (See DeFelice Commentary:
Doctornauts) There is no avoiding this and no amount of legal or ethical
efforts, when it comes to clinical research, can change our risk-averse
To sum it up: Our cultural risk- averse mentality, the corporate and
personal physician costs and risks, the difficulty in obtaining strong
patents, coupled with the federal policy that an investigator must test
every substance and all possible combinations of substances in the
combination therapy in a clinical study, effectively close the door to a
robust and productive anti-aging effort. To make matters worse, I have
not met a single soul that is aware of this sad, truly tragic reality.
When I behold an elderly man who is stooped, walks slowly and carries
a cane, and whose condition will inexorably worsen from week to week, I
am reminded of what the great poet Yeats wrote, " An old man is a
paltry thing." I say to myself, "This need not be. We presently have the
medical technology that can permit him to throw his cane away."
What then is the solution? Paraphrasing President Reagan's famous
words, "Here I go again!" To begin with one answer comes to mind that
will permit the others previously mentioned to be effective: Congress
must enact the Doctornaut Act, which will permit physicians to volunteer
for clinical studies under conditions of significantly reduced costs or
risks to the institutions involved in the studies. I can see no
Without a Doctornaut Act, we must all resign ourselves to the
inevitable trials and tribulations of old age and the cane market will
continue to grow. Butówe will not let this happen. There must, and will
be, a Doctornaut Act for the benefit for all Americans and their