Talk:Gerontology Research Group
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[edit] A History of the GRG by Dr. Stephen Coles
Dr. Steven M. Kaye, M.D. a physician in private practice and I co-founded the Los Angeles Gerontology Research Group back in the Spring of 1990. Subsequently, we met once a month for about six months in each other’s homes and along the way agreed upon a Charter and a Mission Statement for the Group, describing what we hoped could be accomplished in the field of "Anti-Aging Medicine" during our lifetimes. We kept adding to our list on a dedicated white board based on what we knew might become possible someday. Soon, a third person joined us, Dr. Robert Nathan, Ph.D., from the CalTech Jet Propulsion Lab (JPL) , who was also interested in experimental gerontology and attended our monthly meetings for another four or five months. A fourth member, the late Prof. Bernard L. Strehler, Ph.D., a Gerontologist from the University of Southern California, then joined our group. Shortly thereafter, Dr. Steven B. Harris, M.D., from the late Prof. Roy Walford’s lab at UCLA, joined us. From there, the group rapidly expanded to about 15 regular members, including Dr. Joseph Schulman, Ph.D., Chief Scientist for the Alfred E. Mann Foundation.
We started asking extremely detailed questions about what we thought would be feasible within which time frame, recalling that we hoped to achieve something clinically practical in our own lifetimes. We quickly realized that, as a group, we did not have sufficient expertise, so we contacted two graduate students of a well-known Professor of Chemistry at CalTech to give us a lecture on their research involving the direct sequencing of DNA using Atomic-Force Microscopy. We suspected that if we understood DNA sequencing better, we would be on a critical path to understanding the future of Anti-Aging Medicine. That talk, in January of 1991, was our first guest lecture, and since then we have had at least one lecture per month for the past 16 years (including Summers) - ~155 lectures and still going strong! In retrospect, our lecturers have included world-famous researchers in gerontology. We videotaped each lecture and now have an extensive library of VHS tapes and DVD's. Additionally, over the years we have taken a half-dozen field trips to look at different labs (including some now-defunct medical clinics in Mexico).
In recent years, our lectures have been mostly held in a standard lecture hall at the UCLA David Geffen School of Medicine, but at least once a year we have met at USC and at CalTech. For any given lecture, 5 to 10 persons typically attend. About half the lectures are clinical in nature, while the other half focus on the basic sciences (or sometimes on engineering instrumentation), in which we discuss the chemistry and physics of molecular biology. About half of our members are Ph.D.’s and about a quarter are M.D.’s. After each lecture, I generally spend another couple of hours reviewing the latest developments in gerontology and clinical medicine.
Today, the Los Angeles Gerontology Research Group consists of about 160 members: we have also founded Chapters in other cities, such as Washington, D.C. and New York City. About nine years ago, we established our own website (www.grg.org) containing various resources for teaching gerontology, including “Breaking News” and “Editorial Opinions,” particularly about the latest in stem-cell technology. It contains a master list of all of our previous lectures and summaries of the backgrounds of the lecturers. More recently, we established an international Internet Gerontology Discussion Group hosted by computer servers at UCLA with more than 175 researchers worldwide, including members from Australia, England, Scotland, Germany, France, Spain, Portugal, Italy, Canada, as well as the US. It is impossible to predict when I might say something quite innocently, such as, “Aging should not be thought of as a disease but a natural process,” and that could result in a five-week multi-part discussion with many sub-threads running in parallel! Although there are a number of frequent contributors to these discussions, most subscribers remain as quiet observers (lurkers) with what I suspect is amusement or bewilderment while these intense discussions are taking place.
We wrote the original Charter for our organization in the Fall of 1990, and have modified it only slightly, with the consent of the members, maybe ten times over the past 10 years, but only to dot an “i” or cross a “t” here and there. There have been remarkably few changes made in emphasis and only occasional insertions of new jargon, as it becomes fashionable; otherwise, the basic mission of the GRG remains the same as it did 15 years ago - to discover the technical means for intervention in the human aging process within our personal lifetimes (say the next 20 years).
Most recently we have focused on the authentication of the oldest humans in history, a population of so-called Supercentenarians (persons equal to or greater than 110 years old). Since 1998, we have published the most current list of living Supercentenarians (Table E) on our website now updated on a nearly daily basis with Summaries in the Journal of Regenerative Medicine on a bi-monthly basis. On the website we also maintain a photo gallery of over 130 Supercentenarians, which are sent to us as E-mail attachments by interested relatives, nursing-home administrators, and newspaper reporters.
Our interest in this population began when we established a collaboration with the Chairman and Senior Claims Investigator, located in New York and Atlanta, respectively, of an International Supercentenarian Committee. This Committee consists of approximately 30 to 40 demographers, epidemiologists, and other interested hobbyists with representatives in each major country of the world. We typically communicate, seven days a week, almost exclusively by E-mail. We strive to maintain the list of Supercentenarians as accurately as possible. In order to create this database of the world’s oldest people, we established rigorous criteria for entry. A number of unscrupulous individuals (or their friends/family members) have claimed to be very very old, while, in fact, we uncover fraudulent claims - people who have sought to enter The Guinness Book of Records, for example, as being acknowledged to be the world’s oldest living person. Sometimes there is a more mundane motive, such as having avoided military service when they were younger. For example, a young man could sometimes impersonate his father, if he had the same first and last name, using his Birth Certificate or Passport. Because longevity is venerated in some cultures, there may be no incentive later on to switch back to the original correct age. But such claims are obviously invalid, and we have taken it upon ourselves to do the necessary investigative work to identify and expose such fraudulent cases whenever possible.
In order to be included in our official database, an individual needs to have at least three independent sources of documentation: a Birth Certificate (or equivalently a Baptismal Certificate) dated to the original time of birth and not a government issue document say 50 years later, a Marriage Certificate (especially important for women who switch from their maiden name to a married name); and a photo ID of some sort, like a Passport or Driver's License to ensure that they're not an imposter using someone else's documents. For American citizens, consistent US Census records dating back to the years 1900, 1910, 1920, or 1930 can be substituted. A handwritten entry in a family bible is definitely not sufficient, since we have found this source of documentation to be especially error prone. We have even seen one case in which a person’s birth was recorded in a family bible, but the bible was not even published until four years after the stated birthdate! Moreover, since we include persons from countries all over the world, much of the documentation is in various foreign languages; therefore, we require native-language translators for this sort of material. All of our Committee members offer their services on a volunteer basis. We have representatives in many countries, including all of the major European countries, Mexico, Canada, Japan, and Australia. Although we do not yet have any representatives from in China or India, we are actively working to remedy this omission through the offices of the UN World Health Organization (WHO) in Geneva, Switzerland.
We routinely collect and scan into our database all of the documents we require. We record the person’s full name (maiden and married), birth date, the country or state (in the U.S.) where they were born, the country/state where they currently reside, their race and gender, and the name(s) of the committee member(s) or other source responsible for endorsing the validity of the documents. As a result, we have become a de facto world authority on the authentication of these Supercentenarians, without ever intentionally seeking to take on such an important role. As a result, we are regularly contacted by historians and journalists. In particular, we have been contacted by a range of newspaper columnists, residing in every city in the U.S., who write the human-interest side of obituaries of persons who have lived for an unusually long time, not just those who lived in their local area. Today, when one of our listed Supercentenarians dies, we get calls from the major wire services (AP, UPI, Reuters, etc.) and from journalists all over the world who want to know whether this individual was really the age that was claimed by their family (and incidentally what their "secret" may have been). The Guinness Book of World Records in London now employs us as consultants as the authoritative standard for this type of factual information.
So far, the database we publish on our Internet website contains strictly demographic data, along with statistical tables largely of interest to epidemiologists. For example, we recently received a call from a physician with the Social Security Administration who wanted to learn how to cut down on fraud from within their own database by calculating the probability that someone in the US of a given claimed age was likely to still be alive.
Ultimately, however, we hope that this data will become a resource for exploring scientifically interesting questions about what these very old people have in common. When I interview a living Supercentenarians who lives in California, I systematically videotape the interviews and try to learn everything I can about each person’s family history, their medical history, their lifestyle, nutrition, exercise, occupation, religion, etc. Based on the information we have gathered, I can safely testify that these people have almost nothing in common (with a few exceptions). However, we can confidently state that their first-degree relatives (parents and siblings) have also lived a long time (providing that they did not die prematurely of a traumatic injury or in a flu epidemic); however, their spouses generally do not share this fate. Thus, we can say that their siblings (and their children) tend to live a long time as well. So there is something going on in the genes that could explain the inheritance of the longevity phenotype, but we haven't identified what these longevity or "gerontic" genes are yet (this is a polygenic and not a single gene phenotype) and their so-called SNP's (Single Nucleotide Polymorphisms) of the individual genes.
When the public asks us what they themselves can do to live a long time, the rationally-correct answer is “the dice were already rolled when your genes were determined by your parents.” Curiously, many of our Supercentenarians lived what we, today, would call an “unhealthy lifestyle.” One woman who smoked heavily most of her life, and whose doctor had told her consistently that smoking was bad for her, continued to smoke because she enjoyed the habit. She was also fond of pointing out that she had outlived several of such "annoying" doctors. Indeed, as a profession, physicians have virtually no claim to being experts in how to achieve longevity. They don't, in general, live any longer than the population average for where they live. Obstetricians, pediatricians, infectious disease specialists, and public health practitioners as a whole do have an important claim, however. They have collectively have added nearly 30 years to our average life expectancy at birth over the last century, and even tripled it since ancient Roman times. Nevertheless, doctors in general are helpless in the face of extending maximum lifespan, since most of the Supercentenarians in our database never saw a doctor until they were 90 or older, especially those who were born in rural areas. They never needed to, because they were always so healthy. They had no “weak link,” so to speak, in their physical makeup. Also, they never did anything risky enough to cause themselves to be “taken out of the game” by repeated traumatic injuries. Thus, it is very complex to try and predict what component of one's personal lifestyle will help one to live an extremely long time, once one states the trivially obvious precautions, such as “always wear a seat belt.”
But this does not invalidate in any way the routine recommendations that doctors (and dentists) make when they tell their patients to exercise, floss their teeth, take vitamins, never smoke, be scrupulous about not over-indulging in alcohol, and so forth. We do see clear lifestyle differences in longevity in laboratory studies with mice, which are close cousins as mammals. However, people who are lucky in their genetic makeup can get away with a bad lifestyle (including smoking and drinking heavily) and still live for a very, very long time. I would like to make it very clear that they do not live a long time because of bad habits like smoking and drinking heavily. They live a long time in spite of their bad habits. No doctor should recommend that you emulate the poor lifestyle of Supercentenarians in order to try to achieve their extraordinary longevity. That may be a tempting, seductive trap; the real secrets of Supercentenarians lies in their genes, which ever ones helped them to escape from the standard chronic diseases that written on Death Certificates today, like heart disease, cancer, and stroke, for ordinary people in the population. Supercentenarians were lucky in that they did not inherit any “weak links,” so to speak.
If we are going to learn anything about the inheritance of superlongevity, we are going to have to identify the genes that control the aging process itself. Chromosome 4 seems to be an attractive candidate, but a cholesterol-aggregation gene recently discovered by researchers in New York also looks promising. Formal medical studies are underway in the Boston area, where one of our colleagues, Dr. Tom Perls, Director of the New England Centenarian Study, is actively tracking about 150 centenarians. However, his group includes only one Supercentenarian. By contrast, the GRG has chosen not to track people who are “merely” 100 years old, simply because there are literally tens of thousands of them and that's a really daunting task for a volunteer organization.
The next goal of the GRG will not only be to gather historical life-style information, but to do a standard blood-chemistry laboratory analysis. Ultimately, we will need to perform a routine DNA analysis. The cost of DNA sequencing is still extremely expensive today, but in about five years, the price should come down to about $1,000 per sample. That will be a reasonable target, enabling us to preserve tissue samples and to do DNA sequencing on the individuals included in our database.
But what about autopsies as a source of information? Typically, Supercentenarian families are not predisposed toward having a formal autopsy performed. Basically, from their point of view, their relatives are going to die of “old age,” and the families see no need to learn further obscure medical details. Furthermore, there is typically no forensic basis for doing an autopsy by the local coroner's office, since the circumstances are never suspicious. Nevertheless, the GRG would like to know which tissues, like the hair cells from the inner ear or the rods-and-cones of the retina, age more rapidly on average; we should be able to learn a great deal of medically useful information, since many of these persons are blind or deaf or both. In the Pathology Department at UCLA we have performed four Supercentenarian Autopsies out of the seven performed world wide in all of history that we know about. TTR Amyloidosis has been the final diagnosis for three of the four, and we would never have known that without having done a postmortem examination.
Most recently, the GRG has spun off a non-profit Supercentenarian Research Foundation (SRF), a 501(c)(3) tax-exempt corporation, to fund the acquisition of Supercentenarian blood and hair samples (along with first-degree relatives if they're available) for subsequent DNA analysis. This is a highly complex undertaking involving the legal drawing of blood samples (by a licensed phlebotomist) over a wide range of geographical locations, logistics, informed consent, medical privacy, intellectual property, Institutional Review Boards (IRBs) and so on.
So far, all of the work that the GRG and its sister organizations have done has been on a volunteer basis. (The GRG has taken in some small tax-deductible donations over the years, in the range of a few thousand dollars.) Readers who would like to contribute to this cause can receive instructions for how to do so on the SRF website ( http://www.supercentenarianresearchfoundation.org).
-- L. Stephen Coles, M.D., Ph.D., Visiting Scholar, UCLA Department of Computer Science
