“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, AntiAging 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

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Slide 9.

Mortality Rates for Supercentenarians

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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
Secrets of the Oldest Old

November 10, 2007

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.

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Slide 14.

George Francis, 111 yo of Sacramento, CA with his Daughters: Veronica and Shirley

November 10, 2007

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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

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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:
• • • • • • • • • • • • • •
November 10, 2007

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)
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

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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. B. C. D. Left anterior descending artery with [60- 70] percent calcific stenosis Right coronary artery with mild calcific plaque Moderate aortic atherosclerosis 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

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Slide 22.

Brain

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Slide 23.

Left Ventricle Sectioned and Heart

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Slide 24.

Descending Aorta and Kidneys

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Slide 25.

Trachea

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Slide 26.

Thyroid

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Slide 27.

Lung

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Slide 28.

Spine

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Slide 29.

Liver (above) and Spleen (below)

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Slide 30.

Stomach

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Slide 31.

Microscopic Inspection

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Slide 32.

Pituitary

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Slide 33.

Thyroid

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Slide 34.

Heart (Myocytes)

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Slide 35.

Kidney Glomeruli Artery Intimal Thickening

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Slide 36.

Lung Alveoli

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Slide 37.

Bone Marrow

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Slide 38.

Liver

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Slide 39.

Testes
(with a few Sperm present!)

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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.

• 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

SRF Accomplishments

• • • •

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
Secrets of the Oldest Old Slide 45.

November 10, 2007

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

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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
Secrets of the Oldest Old

September 8, 2007

Slide 51.

November 10, 2007

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