Telomere Length as a Predictor for Longevity and Specific Mortality: A Critical Appraisal of the State of Knowledge

Biomarkers for Demographic Research1st European meeting of the Biomarker NetworkAugust 31, 2016David H. Rehkopf

Overview

①  Biology②  Evidence for Associations with Mortality

③  Uses for Biodemography

④  Implementation

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1. Biology

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Pubmed search for Telomere [MeSH term] retrieves 12,453 articles

Why Telomeres?

As mechanism underlying the aging processAs a specific biological indicator of physiological disregulation well prior to mortalityAs fundamental discovery about biology with potential health consequences

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2. Evidence for Association of Telomere Length with Mortality

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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)

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Identification of 7 loci effecting mean telomere length.

Codd at al.

Nature Genetics 2013.

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

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In adjusted models, hazard ratios for shortest quartile:

All-cause1.2 (1.0-1.5)Cardiovascular0.9 (0.5-1.5)Cancer1.2 (0.7-1.9)Other1.5 (1.0-2.1)12

3. Uses of Telomere length

13 Rehkopf, Needham, Lin et al. under review

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15 Rehkopf, Dow, Rosero Bixby et al. 2013

4. Implementation

A.  Tissue + cell type specificB.  DNA storage time

C.  Seasonality

D.  Genetics

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A. Tissue + cell type specific

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B. DNA storage time (preliminary)

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.6.8

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0 10 20 30Individuals

Assay year: 2010 2014 Correction

Correction of 2010 measurement: .345 3.0846 ^ T/S

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

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D. Genetics

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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 course3. Continued collaborations between biological scientists and social scientists on technical issues for implementation in large population based samples 21

Acknowledgements

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Georgetown UniversityDana Glei

Stanford UniversityRita Hamad

University of California, BerkeleyWilliam DowLuis Rosero Bixby

University of California, San FranciscoJue LinElissa EpelElizabeth Blackburn

University of MichiganBelinda Needham

Funding

National Institute on Aging K01 AG047280

Thank you

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drehkopf@stanford.edu@drehkopf