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Cytokine Polymorphisms, Immunosenescence, and Neurodegeneration

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  • First Online:
Handbook of Immunosenescence

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Abstract

The influence of genetics on immunosenescence (age-associated immune deficiency) remains to be resolved. Common genetic variation (polymorphism) that resides within the genes encoding cytokines is an important regulator to positively or negatively affect immunosenescence. Cytokines regulate the type and magnitude of the immune function. Polymorphism can influence the expression level of the cytokine transcript, and thus potentially its corresponding protein, which can subsequently cause an imbalance in the cytokine cascade.

Herein we examine the current literature with respect to cytokine polymorphisms in aging and the age-related neurodegenerative disorder, Parkinson’s disease. Aging studies have identified two cytokine promoter polymorphisms that have shown associations: IL-6 (−174) and IL-10 (−1082). However, other groups have failed to confirm these associations, due in part to studies of limited sample sizes examining a restricted number of cytokine polymorphisms. The inflammatory processes that characterize the cell death that is the hallmark of neurodegenerative disorders such as Parkinson’s disease may also be influenced by cytokine polymorphisms. As with aging, the results to date have been inconsistent, although a number of studies have suggested IL-1β (−511) and TNF-α (−308) show significant association with Parkinson’s disease susceptibility.

Given the complexity of the cytokine network, and the dynamic interplay between anti- and pro-inflammatory aspects, cross-sectional studies examining many cytokine variants in large sample series are now warranted. Genome-wide association studies and the use of whole-exome and whole-genome sequencing strategies may hold promise in elucidating the role of cytokine polymorphisms in the inflammatory processes in both age-related disease and aging.

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Acknowledgments

The Mayo Clinic is a Morris K. Udall Parkinson’s Disease Research Center of Excellence (NINDS P50 NS072187), an Alzheimer’s Disease Research Center (NIA P50 AG16574), NINDS Tau Center without Walls (U54-NS10069) and is supported by The Little Family Foundation, the Mangurian Foundation for Lewy body research, and the Mayo Clinic AD and related dementias’ genetics program. OAR is supported by NINDS R01 NS078086, The Michael J. Fox Foundation, and the Mayo Clinic Foundation and Center of Regenerative Medicine (CRM). The Longevics Program at Mayo Clinic is supported by the Center of Individualized Medicine and benefactor support. We are grateful to our research nurse Anne Murphy and to the Department of Health and Social Services, Northern Ireland, and the Wellcome Trust for funding toward the Belfast Elderly Longitudinal Free-living Aging Study (BELFAST). In memory of Donna J. Hinkle (nee Summers; 1948–2007) and Ann J. Ross (nee O’Malley; 1943–2013).

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Authors and Affiliations

  1. Department of Neuroscience, Mayo Clinic College of Medicine, Jacksonville, FL, USA

    Owen A. Ross, Ronald Walton & Kelly M. Hinkle

  2. Department of Clinical Genomics, Mayo Clinic College of Medicine, Jacksonville, FL, USA

    Owen A. Ross

  3. Department of Biology, University of North Florida, Jacksonville, FL, USA

    Owen A. Ross

  4. School of Medicine and Medical Science, University College Dublin, Dublin, Ireland

    Owen A. Ross

  5. Mayo Graduate School, Neurobiology of Disease Track, Mayo Clinic, Jacksonville, FL, USA

    Owen A. Ross

  6. Department of Neurology, Mayo Clinic College of Medicine, Jacksonville, FL, USA

    Neill Graff-Radford

  7. School of Medicine, Dentistry and Biomedical Science, Queens University of Belfast, Belfast, Northern Ireland, UK

    I. Maeve Rea

  8. Northern Ireland Centre for Stratified Medicine, C-TRIC, Altnagelvin Hospital, Ulster University, Londonderry, Northern Ireland, UK

    I. Maeve Rea

  9. Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK

    I. Maeve Rea

Authors
  1. Owen A. Ross
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  2. Ronald Walton
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  3. Kelly M. Hinkle
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  4. Neill Graff-Radford
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  5. I. Maeve Rea
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Corresponding author

Correspondence to Owen A. Ross .

Editor information

Editors and Affiliations

  1. Division of Geriatrics Research Center on Aging, University of Sherbrooke Dept. of Medicine, Sherbrooke, Québec, Canada

    Tamas Fulop

  2. Dept of Experimental Pathology, University of Bologna, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, Tokyo, Japan

    Katsuiku Hirokawa

  4. Center for Medical Research, University of Tübingen, Tübingen, Germany

    Graham Pawelec

Section Editor information

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Tamas Fulop

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Ross, O.A., Walton, R., Hinkle, K.M., Graff-Radford, N., Rea, I.M. (2018). Cytokine Polymorphisms, Immunosenescence, and Neurodegeneration. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_33-1

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  • DOI: https://doi.org/10.1007/978-3-319-64597-1_33-1

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