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BIOS706 Final Exam

April 17, 2024

Due Thursday May 2, 2024 by 7PM

Please upload your Statistical Analysis Report with complete analysis and interpretation to Sakai.

This is an individual assignment so I expect each person to complete their own analysis and report.  You may use your group SAP template and other materials from class projects if you like.

Please limit your document to 10 pages (but shorter is okay too).  You will need to make thoughtful choices about what to include and what to leave out.  I am expecting a full description of the analysis, clear explanations of results and interpretations along with clean tables and figures.  Don’t forget to summarize your findings.

Testing Biomarkers of Aging in the MIDUS Study

There is great interest in identifying biomarkers of physiological aging, that is substances that can be easily measured over time that would provide an objective measure of biologic age relative to chronological age (Salvioli et al., 2023).  Ideally these biomarkers would provide an early warning of potential conditions and diseases related to aging and would be readily obtainable in blood or urine.    Of particular promise are biomarkers related to inflammation, which has been recognized as associated with aging for many years.  In 1993 Ershler proposed that the cytokine interleukin-6 (IL-6) was an important marker of aging and frailty (Erschler, 1993).  Over time, the importance of IL-6 as a biomarker of aging has not waned and its relationship with individual diseases and multimorbidity continues to be recognized, as laboratories work on identifying the biological mechanisms of aging.  One hypothesis put forward is that dysregulation of IL-6 production is important in the pathogenesis of frailty (Maggio et al. 2006).  As summarized by Maggio et al. IL-6 level increases with age, even after adjustment for confounders.  Further, frail individuals have higher levels of IL-6 than non-frail individuals of the same age, whether frailty is defined by physical measures (Taafe et al. 2000, Cesari et al. 2004), individual diseases (Maggio et al. 2006, Rea et al. 2018), and multimorbidity (St. Sauver et. al 2022).  This relationship between IL-6 and diseases of aging is felt to be so promising that drugs acting on the IL-6 production pathways are in development.  For example Tocilizumab is an antibody to the IL-6 receptor tested for treatment of Crohn’s Disease and rheumatoid arthritis (Maggio et al. 2006).

We are interested in examining the relationship between the biomarker IL-6, aging and frailty in the MIDUS study at two time points.  Please use the materials provided for Project 4 to answer the following questions.

1) Is IL-6 level associated with age?

2) Is healthy aging (or multimorbidity) associated with IL-6 levels in MIDUS 2 (2004-2009)?

3) Is change in healthy aging (or multimorbidity) from MIDUS 2 to MIDUS 3 (2017-2022) associated with IL-6 levels at MIDUS 2 ?

4) Do you think IL-6 would make a good biomarker in studies of aging?

Please make your final exam in the form of a statistical analysis report.  Grading will be based on the elements of your statistical analysis plan similar to those used in the midterm rubric.

This exam draws on concepts we developed for Project 4.  You may use your work from Project 4 as much as you desire.  However, please make sure to include a complete description of your work and cite your Project 4 report when you include work from that group project.  However you may choose a different outcome to represent healthy aging/aging/multimorbidity if you like.

Remember:

1) Your job is to provide a clear report to your collaborators.  They should be able to understand how to talk about the results.

2) Please make sure to be clear about the observations and the sample size.  A cohort diagram can be a big help here.

3) Please include a Table 1 or other clear descriptive table or figure.

4) Please make sure to answer each question.

5) Please make sure to include some discussion.  What are the final conclusions?  How could the analysis be improved?

REFERENCES

Ershler WB. Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc. 1993 Feb;41(2):176-81. doi: 10.1111/j.1532-5415.1993.tb02054.x. PMID: 8426042.

Maggio M, Guralnik JM, Longo DL, Ferrucci L. Interleukin-6 in aging and chronic disease: a magnificent pathway. J Gerontol A Biol Sci Med Sci. 2006 Jun;61(6):575-84. doi: 10.1093/gerona/61.6.575. PMID: 16799139; PMCID: PMC2645627.

Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA. Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines. Front Immunol. 2018 Apr 9;9:586. doi: 10.3389/fimmu.2018.00586. PMID: 29686666; PMCID: PMC5900450.

Taaffe DR, Harris TB, Ferrucci L, Rowe J, Seeman TE. Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons: MacArthur studies of successful aging. J Gerontol A Biol Sci Med Sci. 2000;55A:M709–M715.

Cesari M, Penninx BW, Pahor M, et al. Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci. 2004;59A:242–248.

St Sauver J, Rocca W, LeBrasseur N, Chamberlain A, Olson J, Jacobson D, McGree M, Mielke M. Inflammatory biomarkers, multi-morbidity, and biologic aging. J Int Med Res. 2022 Jul;50(7):3000605221109393. doi: 10.1177/03000605221109393. PMID: 35796512; PMCID: PMC9274410.

Salvioli S, Basile MS, Bencivenga L, Carrino S, Conte M, Damanti S, De Lorenzo R, Fiorenzato E, Gialluisi A, Ingannato A, Antonini A, Baldini N, Capri M, Cenci S, Iacoviello L, Nacmias B, Olivieri F, Rengo G, Querini PR, Lattanzio F. Biomarkers of aging in frailty and age-associated disorders: State of the art and future perspective. Ageing Res Rev. 2023 Nov;91:102044. doi: 10.1016/j.arr.2023.102044. Epub 2023 Aug 28. PMID: 37647997.