“Secrets of the

Oldest Old” by

L. Stephen Coles, M.D., Ph.D., Director

Supercentenarian Research Foundation
664 West Arbor Vitae Street, Suite 1
Inglewood, CA 90301-3160; USA
E-mails: scoles@ucla.edu; scoles@grg.org;
URLs: www.grg.org; www.supercentenarian-research-foundation.org;

Longevity Workshop
Friday, November 16, 2007; [2:00 – 2:30] PM PST
Embassy Suites; El Segundo, CA; USA

November 10, 2007 Secrets of the Oldest Old Slide 1.

 Is There Really an
“Anti-Aging Medicine”?
• Both well-intentioned and deliberately false promises
have been made (over the centuries) by snake oil
salesmen seeking profits at the expense of their gullible
clients
• According to our rigorous scientific colleagues, Anti-
Aging Medicine is still a form of wishful thinking;
indeed, there is no silver bullet that will reverse aging
nor extend human life indefinitely
• But these scientists are not responsible for treating
patients in the “here and now,” and as physicians, we
have a responsibility to our patients
• So, how should we deal with this inherent paradox?
October 29, 2004 Slide 2.
 Argument: Here’s Why We
Should Not Give Up Hope
• The best is yet to come.
• But, if real Life Extension is
still some years away, in
order to benefit, we need to
be here, if and when it does
come. (And we will surely be
among the first to know.)
• And for that, we will need a
“Bridge Plan” to make sure
we are still here.
Thomas Kinkade “The Bridge of Hope”

October 29, 2004 Slide 3.

Arthur C. Clarke,
“The Hazards of Prophecy,”
Playboy Magazine, Vol. 9,
No. 3, p. 102 (July 1962).
Robert Paul Smith, "A Low Bid for Immortality,” Playboy
Magazine, Vol. 7, No. 8 (August 1960).
I wrote to Clarke c/o Playboy with a proposal following up
on his suggestion that “we establish a new scientific
organization to engineer ‘immortality’.”
Sir Arthur wrote back to me in about a month’s time on his
personal stationary from his Technopolis Compound in
Sri Lanka (Ceylon) “… wishing me luck.”

October 29, 2004 Slide 4.

October 29, 2004 Slide 5.
 Profiles of the Future [1960… 2000]

September 8, 2007 Secrets of the Oldest Old Slide 6.

 Supercentenarians

November 10, 2007 Secrets of the Oldest Old Slide 7.

 Who is a Supercentenarian?
• While a Centenarian is anyone age 100 years or older,
(Only 1 in 10,000 persons makes it into this category)
• A Supercentenarian is anyone age 110 years or older
(And only 1 in 5 million persons makes it into this category)
• As of today (November 16th), there are 75 Validated Living
Supercentenarians World Wide (USA : nonUS = 31 : 44)
(Female : Male = 69 : 6)
• Oldest documented Supercentenarian in history was French
woman Madame Jeanne-Louise Calment, who died in 1997 at
122 years, 164 days
• Once you were to make it to becoming a Supercentenarian,
the chances of living even one more year is like flipping a coin
(H:T = 50-50)!
• Therefore, these individuals are a very precious resource for
humanity, and we need to act quickly; otherwise, whatever
they have to teach us will be gone forever
November 10, 2007 Secrets of the Oldest Old Slide 8.
 Mortality Rates for
Supercentenarians

November 10, 2007 Secrets of the Oldest Old Slide 9.

 Mortality Rates for
Supercentenarians

November 10, 2007 Secrets of the Oldest Old Slide 10.

 How Can Supercentenarians Help Us
To Live Longer and Healthier Lives?

• Compression of Morbidity that will lead to

a healthier life in one’s later years
(present company excepted)

• Gene Discovery Program

• Stem-Cell Advances
• New pharmaceutical interventions with
obvious commercial implications

November 10, 2007 Secrets of the Oldest Old Slide 11.

 Why Do Supercentenarians Live So Long?
• The most likely cause of death of Supercentenarians is
called Senile Cardiac TTR-Amyloidosis (This diagnosis
is by Autopsy [4 of 8 in all of history] and not by what
is written on Death Certificates)
• Finding: We recognize that longevity is inherited
(1st-degree relatives [parents/sibs] also live a long time);
BTW, Supercentenarians have practically
nothing else in common, regardless of what they tell us
is their self-attributed “Secret” to exceptionally long life
• Conclusion: The secret to longevity must lie somewhere
in our genes
• Corollary: The first step is to do a simple DNA SNP
Analysis (Single Nucleotide Polymorphism) that is
expected to uncover a large number of “gerontic” genes
which determine both life expectancy and maximum
human lifespan
November 10, 2007 Secrets of the Oldest Old Slide 12.
 CNN –TV on SRF
(December 19, 2006; 8:39 AM PST;
TRT = ~3 min.)

November 10, 2007 Secrets of the Oldest Old Slide 13.

November 10, 2007 Secrets of the Oldest Old Slide 14.
George Francis, 111 yo of Sacramento, CA with his
Daughters: Veronica and Shirley

November 10, 2007 Secrets of the Oldest Old Slide 15.

 Pvt. George H. Johnson, 112 yo,
was the Oldest Person in California at the time he died.
{Mother, 111, 110, 110, 112, Coles + Brian Johnson, Great Nephew}

November 10, 2007 Secrets of the Oldest Old Slide 16.

 Pvt. George H. Johnson, 112 yo,
Supercentenarian Veteran of World War I
Funeral Services (September 6, 2006)

November 10, 2007 Secrets of the Oldest Old Slide 17.

 Pvt. George H. Johnson, 112 yo
[May 1, 1894 – August 30, 2006]
Autopsy performed at the Palo Alto VA Hospital on August 31, 2006
and later at the UCLA David Geffen School of Medicine

Summary:
• Lungs: Bilateral Bronchopneumonia (Pleural Effusion)(No growth of bacteria in
culture) Pleural Adhesions, secondary to inflammation?
• Brain: Unremarkable (Minor senile changes of the Alzheimer’s type)
• Heart: Clean (no atherosclerosis); Descending Aorta: Clean)
• Spine: Severe Osteoporosis (Left Shift of Bone Marrow)
• Pancreas: Fibrosis and Atrophy
• Liver: Acute Congestion
• Gall Bladder (one small stone)
• Testes: Atrophic
• Prostate: Severe BPH (clinical complaint was consistent)
• Kidneys: pyelonephritis; ischemic atrophy; nephrosclerosis
• Urinary Bladder: Trabeculated
• Colon: Diverticula
• Thyroid: Moderately Enlarged
• Eyes: Blindness, secondary to Glaucoma (Clinical Dx: 04/15/97)
November 10, 2007 Secrets of the Oldest Old Slide 18.
 Palo Alto VA Hospital
Preliminary Necropsy Diagnosis

November 10, 2007 Secrets of the Oldest Old Slide 19.

 Mr. William Seegers, 106 yo

November 10, 2007 Secrets of the Oldest Old Slide 20.

 Palo Alto VA Hospital
Preliminary Necropsy Diagnosis
William SEEGERS, Date Died: 07/10/07; Prosector: Mathew Anderson, M.D., Ph.D.
Date of Autopsy: 07/16/07; Permit: Full; Report: 07 A-58

1. Atherosclerosis, Generalized Moderate

A. Left anterior descending artery with [60- 70] percent calcific stenosis
B. Right coronary artery with mild calcific plaque
C. Moderate aortic atherosclerosis
D. Renal cortical scarring, bilateral, mild
2. Urinary Bladder with Intraluminal Blood Clot (Hx of UTI)
3. Bilateral Pleural Effusions (300 cc)
4. Concentric Left Ventricular Hypertrophy
November 10, 2007 Secrets of the Oldest Old Slide 21.
 Gross Anatomical Inspection

Microscopic Inspection

November 10, 2007 Secrets of the Oldest Old Slide 22.

 Brain

November 10, 2007 Secrets of the Oldest Old Slide 23.

 Left Ventricle Sectioned
and Heart

November 10, 2007 Secrets of the Oldest Old Slide 24.

 Descending Aorta and Kidneys

November 10, 2007 Secrets of the Oldest Old Slide 25.

 Trachea

November 10, 2007 Secrets of the Oldest Old Slide 26.

 Thyroid

November 10, 2007 Secrets of the Oldest Old Slide 27.

 Lung

November 10, 2007 Secrets of the Oldest Old Slide 28.

 Spine

November 10, 2007 Secrets of the Oldest Old Slide 29.

 Liver (above) and Spleen (below)

November 10, 2007 Secrets of the Oldest Old Slide 30.

 Stomach

November 10, 2007 Secrets of the Oldest Old Slide 31.

 Microscopic Inspection

November 10, 2007 Secrets of the Oldest Old Slide 32.

 Pituitary

November 10, 2007 Secrets of the Oldest Old Slide 33.

 Thyroid

November 10, 2007 Secrets of the Oldest Old Slide 34.

 Heart (Myocytes)

November 10, 2007 Secrets of the Oldest Old Slide 35.

 Kidney Glomeruli
Artery Intimal Thickening

November 10, 2007 Secrets of the Oldest Old Slide 36.

 Lung Alveoli

November 10, 2007 Secrets of the Oldest Old Slide 37.

 Bone Marrow

November 10, 2007 Secrets of the Oldest Old Slide 38.

 Liver

November 10, 2007 Secrets of the Oldest Old Slide 39.

 Testes
(with a few Sperm present!)

November 10, 2007 Secrets of the Oldest Old Slide 40.

 Acknowledgements:
• Palo Alto Veteran’s Administration Hospital
(PAVA)
Dr. Robert Rouse, M.D., Chief of Service
Dr. Jon Kosek, M.D., Deputy Chief of Service
Prof. Robert B. West, M.D., Ph.D., Department of Pathology;
Sanford University School of Medicine
Dr. Mathew Anderson, M.D., Ph.D., Chief Resident

• Department of Pathology and Laboratory Medicine

UCLA David Geffen School of Medicine
Prof. Michael C. Fishbein, M.D., Chief-of-Service
Prof. Harry V. Vinters, M.D., Chief of Neuropathology

November 10, 2007 Secrets of the Oldest Old Slide 41.

 Supercentenarian Research Foundation
(SRF)

November 10, 2007 Secrets of the Oldest Old Slide 42.

 What is the SRF?
• A non-profit research foundation that seeks to
exploit the knowledge that will be acquired from
discovering two facts about Supercentenarians:
– Why do they live as long as they do?
(How do they escape from chronic diseases, like Heart
Disease, Cancer, Stroke, Diabetes, and Alzheimer’s
Disease, which are the top diagnoses written today on
Death Certificates in the US and limit the average life
expectancy of older Americans?)
– Why don’t they live longer than they do?
(TTR Amyloidosis could be the Grim Reaper waiting in the
wings for everyone, unless we figure out what to do about
it first)
November 10, 2007 Secrets of the Oldest Old Slide 43.
 SRF PROGRESS

• What has the SRF already accomplished?

• What does the SRF propose to do next?
• What are the barriers to entry?
• What is the long-term significance of our
success?
• What are our next steps?

November 10, 2007 Secrets of the Oldest Old Slide 44.

 SRF Accomplishments
• Through the Gerontology Research Group (GRG) at UCLA, the
SRF has accumulated 8 years of historical data regarding all
validated Supercentenarians
• The GRG database is one of the most respected sources of reliable
information regarding Supercentenarians and is routinely used as
the premier source for yearly articles in The Guinness Book of
Records of London. Reuters, AP, and UPI wire services now
considers the GRG to be the world authority on the demographics
of longevity
• Our SRF Website is posted at
http://www.supercentenarian-research-foundation.org
• Foundation was incorporated in Harrisburg, PA; Sacramento, CA
• 501(c)(3) IRS Form 1023 Tax Exempt Status
• Raised $150,000 in charitable donations for our start-up expenses
• Established a Scientific Advisory Board consisting of 38 members
including many of the world-recognized experts in aging research
November 10, 2007 Secrets of the Oldest Old Slide 45.
 GRG: Recent Activities

Stephen Coles, James D. Watson, Pumpkin at Albert Einstein’s

Stan Primmer at Cold Spring Home in Princeton, New Jersey
Harbor Laboratory, New York

November 1, 2007 Secrets of the Oldest Old Slide 46.

 Future Plans
Q: What does the SRF plan to do next?
A: First Project [for 2007]: Tissue Sampling of all known
Supercentenarians world wide whose next-of-kin are willing
to sign our Informed Consent (in their native language giving
us ownership of all specimens) and their first-degree relatives
[sibs/children] agree to serve as controls…
– DNA-SNP and DNA-Repeats Analysis in the lab
– This will establish an invaluable database and tissue bank for
researchers world wide of materials that would otherwise be lost
forever
– Later, the information generated by this database may result in
insights and products that could improve the quality of life and
longevity of everyone

November 10, 2007 Secrets of the Oldest Old Slide 47.

 Barriers to Entry?
• Q: What groups are doing this (or are
likely to be doing the same thing in the
near future)?

• A: None that we know of are exclusively

devoted to the task of sampling the
tissues of Supercentenarians, although
three groups are doing centenarians
November 10, 2007 Secrets of the Oldest Old Slide 48.
 Long-Term Significance

Q: Why it matters to history?

A: Potentially, this could be the most

important scientific breakthrough in
the history of our human species
(~200,000 years)

November 10, 2007 Secrets of the Oldest Old Slide 49.

 Next Steps?
Together we can unlock the secrets to a
higher quality life, longevity, and health

Please consider joining and supporting the

SRF and making healthy longevity a
reality for everyone

November 10, 2007 Secrets of the Oldest Old Slide 50.

 GRG Discussion Group
• There are 184 members of the Gerontology
Research Group Discussion Group, hosted
by UCLA, that send [10-15] messages-a-day
to one another, seven days a week
• Contact me to join if you are personally
interested in expressing your opinions on
breaking news in this exciting field

September 8, 2007 Secrets of the Oldest Old Slide 51.

November 10, 2007 Secrets of the Oldest Old