An overview of research on telomere length and mortality, including a consideration of observational data and genetic instrumental variable analysis, as well as a primer on practical technical issues of doing studies on telomere length to understand biological aging.

1. Telomere Length as a Predictor for
Longevity and Specific Mortality:
A Critical Appraisal of the State of Knowledge
Biomarkers for Demographic Research
1st European meeting of the Biomarker Network
August 31, 2016
David H. Rehkopf

2. Overview
① Biology
② Evidence for Associations with Mortality
③ Uses for Biodemography
④ Implementation
2

3. 1. Biology
3
Pubmed search for Telomere [MeSH term]
retrieves 12,453 articles

4. Why Telomeres?
As mechanism underlying the aging process
As a specific biological indicator of physiological
disregulation well prior to mortality
As fundamental discovery about biology with
potential health consequences
4

5. 2. Evidence for Association of
Telomere Length with Mortality
5

6. Pooled relative risk
of coronary heart
disease
1.54 (1.30-1.83)
comparing shortest
third of population to
longest third of
population on
leukocyte telomere
length.
Among those
controlling for most
confounders:
1.34 (1.04-1.74)
6

7. Identification
of 7 loci
effecting
mean
telomere
length.
Codd at al.
Nature
Genetics
2013.
7

8. 8

9. 9

10. 10

11. n=3,091, events=870 deaths, 9.5 years follow-up
11

12. In adjusted models,
hazard ratios for
shortest quartile:
All-cause
1.2 (1.0-1.5)
Cardiovascular
0.9 (0.5-1.5)
Cancer
1.2 (0.7-1.9)
Other
1.5 (1.0-2.1) 12

13. 3. Uses of Telomere length
13
Rehkopf, Needham, Lin et al. under review

14. 14

15. 15
Rehkopf, Dow, Rosero Bixby et al. 2013

16. 4. Implementation
A. Tissue + cell type specific
B. DNA storage time
C. Seasonality
D. Genetics
16

17. A. Tissue + cell type specific
17

18. B. DNA storage time (preliminary)
18
.6.811.21.4
T/Sratio(logscale)
0 10 20 30
Individuals
Assay year: 2010 2014 Correction
Correction of 2010 measurement: .345 3.0846 ^ T/S

19. C. Seasonality
Difference in
telomere length
between those
60-74 years old
and those 95+:
321 base pairs
Difference in
telomere length
between blood
collected in May
and November:
200 base pairs
19

20. D. Genetics
20

21. Conclusions
1. For leukocyte telomere length, not a
strong predictor of mortality, in
particular much weaker than many other
measures for short-term mortality.
Evidence strongest for cardiovascular
disease mortality.
2. Most potentially useful as 1)
complement to other biomarkers of
aging, 2) to capture biological age earlier
in the life course
3. Continued collaborations between
biological scientists and social scientists
on technical issues for implementation in
large population based samples 21

22. Acknowledgements
22
Georgetown University
Dana Glei
Stanford University
Rita Hamad
University of California, Berkeley
William Dow
Luis Rosero Bixby
University of California, San Francisco
Jue Lin
Elissa Epel
Elizabeth Blackburn
University of Michigan
Belinda Needham
Funding
National Institute on Aging
K01 AG047280

23. Thank you
23
drehkopf@stanford.edu
@drehkopf