Telomere Maintenance: Chronic Pain in the Context of Premature Aging

9th Annual Lindahl Lecture

Telomere Maintenance: Chronic Pain in the Context of Premature Aging

Learning Objectives

As a result of participating in this activity, learners will be able/better able to:

• Monitor signs of premature ageing among chronic pain patients
• Work with patients to mitigate their stress

Introduction

Telomere length, a measure of cellular aging, is inversely associated with chronic pain severity.

Overview

Our curiosity-driven, basic science research was first aimed at understanding, at a molecular level, how cells protect their chromosomal ends (telomeres). Beginning with model organism systems, our subsequent research has led to collaborative discoveries that include understanding of disease processes in humans and optimizing human health.

In this lecture, I briefly explain the fundamental and clinical science discoveries, then discuss the growing evidence that life-long factors impact on telomeres, and may reverberate throughout the life course to affect health. These factors start from earliest life and include nutrition and conditions of pregnancy, and societal and environmental factors. Hence this research has led to broader, including societal, implications.

Outline

• Basic science
  • Cellular effects of lack of telomere maintenance
• Human genetics
  • Causal relationships of telomere maintenance and human diseases
• Human studies
  • Correlations - including pain; non-genetic factors influencing telomeres in people
• Interactions of telomere attrition with other factors
• Broader implication 

Desirable Physician Attributes

• Medical Knowledge [ACGME/ABMS] about established and evolving biomedical, clinical, and cognate (e.g. epidemiological and social-behavioral) sciences and the application of this knowledge to patient care
  
• Employ Evidence-based Practice [IOM] Integrate best research with clinical expertise and patient values for optimum care and participate in learning and research activities to the extent feasible
• Patient Care [ACGME/ABMS] Provide care that is compassionate, appropriate and effective for the treatment of health problems and the promotion of health

Accreditation & Designation

Release date: This activity was released 8/27/2021.

Termination date: The content of this activity remains eligible for CME Credit until 8/26/2024, unless reviewed or amended prior to this date.

Neurovations Education is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Neurovations Education designates this other activity (blended learning) for a maximum of 1.00 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Disclosure of Financial Relationships

Neither the presenter, reviewers nor any other person with control of, or responsibility for, the planning, delivery, or evaluation of accredited continuing education has, or has had within the past 24 months, any financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

Additional Reading

• Greider, C. W., & Blackburn, E. H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell, 43(2), 405-413.
• Blackburn, E. H., Greider, C. W., & Szostak, J. W. (2006). Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nature Medicine, 12(10), 1133-1138.
• Greider, C. W., & Blackburn, E. H. (1996). Telomeres, telomerase and cancer. Scientific American, 274(2), 92-97.
• Hassett, A. L., Epel, E., Clauw, D. J., Harris, R. E., Harte, S. E., Kairys, A., ... & Williams, D. A. (2012). Pain is associated with short leukocyte telomere length in women with fibromyalgia. The Journal of Pain, 13(10), 959-969.
• Alhareeri, A. A., Archer, K. J., Fu, H., Lyon, D. E., Elswick, R. K., Kelly, D. L., ... & Jackson-Cook, C. K. (2020). Telomere lengths in women treated for breast cancer show associations with chemotherapy, pain symptoms, and cognitive domain measures: a longitudinal study. Breast Cancer Research, 22(1), 1-18.
• Steward, A. M., Morgan, J. D., Espinosa, J. P., Turk, D. C., & Patel, K. V. (2017). Chronic pain and telomere length in community-dwelling adults: Findings from the 1999 to 2002 national health and nutrition examination survey. The Journal of Pain, 18(12), 1517-1525.
• Arsenis, N. C., You, T., Ogawa, E. F., Tinsley, G. M., & Zuo, L. (2017). Physical activity and telomere length: Impact of aging and potential mechanisms of action. Oncotarget, 8(27), 45008.
• Sibille, K. T., Chen, H., Bartley, E. J., Riley III, J., Glover, T. L., King, C. D., ... & Fillingim, R. B. (2017). Accelerated aging in adults with knee osteoarthritis pain: consideration for frequency, intensity, time, and total pain sites. Pain Reports, 2(3).
• Fedorchuk, C., Lightstone, D. F., McCoy, M., & Harrison, D. E. (2017). Increased telomere length and improvements in dysautonomia, quality of life, and neck and back pain following correction of sagittal cervical alignment using Chiropractic BioPhysics® technique: a case study. J. Mol Genet Med, 11(269), 1747-0862.
• Epel, E., Daubenmier, J., Moskowitz, J. T., Folkman, S., & Blackburn, E. (2009). Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres.
• Doksani, Y., Wu, J. Y., de Lange, T., & Zhuang, X. (2013). Super-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formation. Cell, 155(2), 345-356.
• López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
• Johnson, A. J., Terry, E., Bartley, E. J., Garvan, C., Cruz-Almeida, Y., Goodin, B., ... & Sibille, K. T. (2019). Resilience factors may buffer cellular aging in individuals with and without chronic knee pain. Molecular Pain, 15, 1744806919842962.
• Lahav, Y., Levy, D., Ohry, A., Zeilig, G., Lahav, M., Golander, H., ... & Defrin, R. (2021). Chronic Pain and Premature Aging–The Moderating Role of Physical Exercise. The Journal of Pain, 22(2), 209-218.
• Armanios, M. (2013). Telomeres and age-related disease: how telomere biology informs clinical paradigms. The Journal of Clinical Investigation, 123(3), 996-1002.
• Wang, Q., Zhan, Y., Pedersen, N. L., Fang, F., & Hägg, S. (2018). Telomere length and all-cause mortality: a meta-analysis. Ageing Research Reviews, 48, 11-20.
• Lapham, K., Kvale, M. N., Lin, J., Connell, S., Croen, L. A., Dispensa, B. P., ... & Blackburn, E. H. (2015). Automated assay of telomere length measurement and informatics for 100,000 subjects in the genetic epidemiology research on adult health and aging (GERA) cohort. Genetics, 200(4), 1061-1072.
• Goglin, S. E., Farzaneh-Far, R., Epel, E. S., Lin, J., Blackburn, E. H., & Whooley, M. A. (2016). Change in leukocyte telomere length predicts mortality in patients with stable coronary heart disease from the heart and soul study. PloS one, 11(10), e0160748.
• Sapolsky, R. M. (2004). Organismal stress and telomeric aging: An unexpected connection. Proceedings of the National Academy of Sciences, 101(50), 17323-17324.
• Entringer, S., Epel, E. S., Kumsta, R., Lin, J., Hellhammer, D. H., Blackburn, E. H., ... & Wadhwa, P. D. (2011). Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proceedings of the National Academy of Sciences, 108(33), E513-E518.