SENS3 presentations of Steve Coles, Los Angeles, USA Secrets of the oldest old

1. “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-mail’s: scoles@ucla.edu; scoles@grg.org;
URL’s: www.grg.org; www.supercentenarian-research-foundation.org;
Thursday, September 6, 2007; [3:35 – 3:50] PM GMT
SENS-3 Conference; Cambridge; UK
September 6, 2007 Secrets of the Oldest Old Slide 1.

2. 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 (September 6th), there are 75 Validated Living
Supercentenarians World Wide (US: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 else whatever they have
to teach us will be gone forever
Secrets of the Oldest Old
September 6, 2007 Slide 2.

3. Two British Living
Supercentenarians
• Flore Baldwin, 111 W F
• Henry Allingham, 111 W M
Secrets of the Oldest Old
September 6, 2007 Slide 3.

4. Mortality Rates for
Supercentenarians
Secrets of the Oldest Old
September 6, 2007 Slide 4.

5. Mortality Rates for
Supercentenarians
Secrets of the Oldest Old
September 6, 2007 Slide 5.

6. 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
September 6, 2007 Slide 6.

7. Why Do Supercentenarians Live So Long?
• The most likely cause of death of Supercentenarians is
called Senile Cardiac TTR-Amyloidosis (Diagnosis 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 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 long life
• Conclusion: The answer to longevity must lie in our
genes
• Corollary: Doing a simple DNA Single Nucleotide
Polymorphism (SNP) analysis is expected to uncover a
large number of “longevity” genes that determine
human life expectancy and maximum lifespan
Secrets of the Oldest Old
September 6, 2007 Slide 7.

8. CNN –TV on SRF
(December 19, 2006; 8:39 AM PST;
TRT = ~3 min.)
Secrets of the Oldest Old
September 6, 2007 Slide 8.

9. Secrets of the Oldest Old
September 6, 2007 Slide 9.

10. George Francis, 111 yo of Sacramento, CA with his
Daughters: Veronica and Shirley
Secrets of the Oldest Old
September 6, 2007 Slide 10.

11. 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}
Secrets of the Oldest Old
September 6, 2007 Slide 11.

12. Mr. W.S., 106 yo,
was the Third Oldest Person in California at the time he died.
Secrets of the Oldest Old
September 6, 2007 Slide 12.

13. Palo Alto VA Hospital
Preliminary Necropsy Diagnosis
W.S., 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
Secrets of the Oldest Old
September 6, 2007 Slide 13.

14. Microscopic Inspection
Secrets of the Oldest Old
September 6, 2007 Slide 24.

15. Pituitary
Secrets of the Oldest Old
September 6, 2007 Slide 25.

16. Thyroid
Secrets of the Oldest Old
September 6, 2007 Slide 26.

17. Heart (Myocytes)
Secrets of the Oldest Old
September 6, 2007 Slide 27.

18. Kidney Glomeruli
Artery Intimal Thickening
Secrets of the Oldest Old
September 6, 2007 Slide 28.

19. Lung Alveoli
Secrets of the Oldest Old
September 6, 2007 Slide 29.

20. Bone Marrow
Secrets of the Oldest Old
September 6, 2007 Slide 30.

21. Liver
Secrets of the Oldest Old
September 6, 2007 Slide 31.

22. Testicle
(with Sperm Present!)
Secrets of the Oldest Old
September 6, 2007 Slide 32.

23. 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
Secrets of the Oldest Old
September 6, 2007 Slide 33.

24. Supercentenarian Research Foundation
(SRF)
Secrets of the Oldest Old
September 6, 2007 Slide 34.

25. What is the SRF?
• A non-profit research foundation that seeks to
exploit the knowledge that will be acquired from
discovering:
– Why Supercentenarians 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 they don’t 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)
Secrets of the Oldest Old
September 6, 2007 Slide 35.

26. SRF PROGRESS
• What has the SRF already accomplished?
• What does the SRF propose to do next?
• What is the long-term significance of our
success?
• What are our next steps?
Secrets of the Oldest Old
September 6, 2007 Slide 36.

27. 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
Secrets of the Oldest Old
September 6, 2007 Slide 37.

28. 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
agree to serve as controls…
– DNA SNP 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
Secrets of the Oldest Old
September 6, 2007 Slide 38.

29. 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)
Secrets of the Oldest Old
September 6, 2007 Slide 39.

30. 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
Secrets of the Oldest Old
September 6, 2007 Slide 40.