Advertisement

Telomere Length Analysis: A Tool for Dissecting Aging Mechanisms in Developmental Programming

Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1735)

Abstract

Accelerated cellular aging is known to play an important role in the etiology of phenotypes associated with developmental programming, such as cardiovascular disease and type 2 diabetes. Telomere length analysis is a powerful tool to quantify cellular aging. Here we describe a telomere length methodology, refined to quantify discrete telomere length fragments. We have shown this method to be more sensitive in detecting small changes in telomere length than the traditional average telomere length comparisons.

Key words

Developmental programming Telomere length analysis Pulsed field gel electrophoresis Southern blotting 

Notes

Acknowledgments

The authors are members of the University of Cambridge MRC Metabolic Disease Unit and are funded by the UK Medical Research Council (MC UU12012/04).

References

  1. 1.
    Hales CN, Barker DJ, Clark PM, Cox LJ, Fall C, Osmond C et al (1991) Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 303:1019–1022CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM (1993) Type 2 (non-insulin dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to fetal growth. Diabetes 36:62–67Google Scholar
  3. 3.
    Fall CHD, Osmond C, Barker DJP, Clark PMS, Hales CN, Stirling Y et al (1995) Fetal and infant growth and cardiovascular risk factors in women. BMJ 310:428–432CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Tarry-Adkins JL, Ozanne SE (2011) Mechanisms of early life programming: current knowledge and future directions. Am J Clin Nutr 94:1765S–1771SCrossRefPubMedGoogle Scholar
  5. 5.
    Tarry-Adkins JL, Ozanne SE (2017) Nutrition in early life and age-associated diseases. Ageing Res Rev 39:96–105CrossRefPubMedGoogle Scholar
  6. 6.
    Blackburn EH (1984) The molecular structure of centromeres and telomeres. Annu Rev Biochem 53:163–194CrossRefPubMedGoogle Scholar
  7. 7.
    Olovnikov AM (1996) Telomeres, telomerase and aging: origin of the theory. Exp Gerontol 31:443–448CrossRefPubMedGoogle Scholar
  8. 8.
    von Zglinicki T (2000) Role of oxidative stress in telomere length regulation and replicative senescence. Ann N Y Acad Sci 908:99–110CrossRefGoogle Scholar
  9. 9.
    Sharpless NE, de Pinto RA (2004) Telomeres, stem cells, senescence and cancer. J Clin Invest 113:160–168CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Lenart P, Krejci L (2016) DNA, the central molecule of aging. Mutat Res 786:1–7CrossRefPubMedGoogle Scholar
  11. 11.
    Jaskelioff M, Muller FL, Paik JH, Thomas E, Jiang S, Adams AC et al (2011) Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469(7328):102–106CrossRefPubMedGoogle Scholar
  12. 12.
    Blasco MA (2005) Telomeres and human disease: ageing, cancer and beyond. Nat Rev Genet 13:611–622CrossRefGoogle Scholar
  13. 13.
    Haycock PC, Heydon EE, Kaptoge S, Butterworth AS, Thompson A, Willeit P (2014) Leucocyte telomere length and risk of cardiovascular disease: systemic review and meta-analysis. BMJ 349:g4227.  https://doi.org/10.1136/bmj.g4227 CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Zhao J, Miao K, Wang H, Ding H, Wang DW (2013) Association between telomere length and type 2 diabetes mellitus: a meta-analysis. PLoS One 8:e79993.  https://doi.org/10.1371/journal.pone.0079993 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cawthorn RM, Smith KR, O’Brien E, Sivatchenko A, Kerber RA (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361(9355):393–395CrossRefGoogle Scholar
  16. 16.
    Heidinger BJ, Blount JD, Boner W, Griffiths K, Metcalfe NB, Monaghan P (2012) Telomere length in early life predicts lifespan. Proc Natl Acad Sci U S A 109:1743–1748CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Nussey DH, Baird D, Barrett E, Boner W, Fairlie J, Gemmell N et al (2014) Measuring telomere length and telomere dynamics in evolutionary biology and ecology. Methods Ecol Evol 5:299–310CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cherif C, Tarry JL, Ozanne SE, Hales CN (2003) Ageing and telomeres: a study into organ- and gender-specific telomere shortening. Nucleic Acid Res 31:1576–1583CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Tarry-Adkins JL, Joles JA, Chen JH, Martin-Gronert MS, van der Giezen DM, Goldschmeding R et al (2007) Protein restriction in lactation confers nephroprotective effects in the male rat and is associated with increased antioxidant expression. Am J Physiol Regul Integr Comp Physiol 293:R1259–R1266CrossRefPubMedGoogle Scholar
  20. 20.
    Tarry-Adkins JL, Martin-Gronert MS, Chen JH, Cripps RL, Ozanne SE (2008) Maternal diet influences DNA damage, aortic telomere length, oxidative stress and antioxidant capacity in rats. FASEB J 22:2037–2044CrossRefPubMedGoogle Scholar
  21. 21.
    Tarry-Adkins JL, Chen JH, Smith NS, Jones RH, Cherif H, Ozanne SE (2009) Poor maternal nutrition followed by accelerated catch up growth leads to telomere shortening and increased markers of cell senescence in rat islets. FASEB J 23:1521–1528CrossRefPubMedGoogle Scholar
  22. 22.
    Aiken CE, Tarry-Adkins JL, Ozanne SE (2013) Suboptimal nutrition in utero causes DNA damage and accelerated aging of the female reproductive tract. FASEB J 27:3959–3965CrossRefPubMedGoogle Scholar
  23. 23.
    Hemann MT, Strong MA, Hao LY, Greider CW (2001) The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107:67–77CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2018

Authors and Affiliations

  1. 1.MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic ScienceAddenbrooke’s HospitalCambridgeUK

Personalised recommendations