AS191 - Biomarkers and genetic factors related to sarcopenia in older women (includes AS199)
Investigator Names and Contact Information
Zhao Chen (zchen@u.arizona.edu)
Introduction/Intent
AS191 summary and aims
Older women have a higher risk for physical function impairment and disability in comparison to older men. Low relative skeletal muscle mass (SMM) or sarcopenia contributes to the decline in physical functions among the elderly. The primary objective of this study is to investigate biological mechanisms for sarcopenia and to identify biomarkers that predict SMM loss. There are two specific aims: to assess the association of cytokines and hormonal factors with sarcopenia and the rate of SMM loss, and to investigate the sensitivity and specificity of these biomarkers in predicting SMM loss. A case-cohort study design will be used to include 400 cases and 1000 randomly selected women from the entire WHI OS DXA (Dual-energy X-ray Absorptiometry) cohort. The cases are defined as women with the highest (top 10%) rate of SMM loss during the follow-up. SMM is assessed in an ongoing WHI ancillary study (AS#153, PI: Zhao Chen). The biomarkers that will be measured in this study are IL-1a, IL-1b, IL-6, IL-10, TNF-a, TNF-b, Growth Hormone, Insulin, Leptin, C-reactive protein, IL-1ra, IL-6sR, TNF RII, IGF-1, IGFBP-1 and IGFBP-3. The modified multivariate analysis for case-cohort studies and the ROC analysis will be used. This study is unique and innovative in the study design, selection of bioassays and the study population and will have significant impacts on women’s health.
Aims
Loss of skeletal muscle mass (SMM) often occurs in older populations even in the absence of overt disease. Many diseases and conditions, such as chronic rheumatic diseases, may further accelerate muscle loss, and increase a person’s risk for sarcopenia (very low SMM), a condition that leads to declined physical functions and poor quality of life in older age. Increased levels of inflammatory factors and lower levels of IGF are associated with low skeletal muscle mass, suggesting that changes in levels of cytokines and hormonal factors with aging may be potential mechanisms for loss of SMM. The specificity and sensitivity of these biomarkers in assessing acute changes in skeletal muscle, and in screening and predicting skeletal muscle loss in longitudinal follow-up have not been fully investigated.
Our primary objective is to investigate the biological mechanisms for sarcopenia and to identify biomarkers that predict changes in skeletal muscle mass. The specific aims of this study include:
- To assess the association of cytokines and hormonal factors with sarcopenia and rate of SMM loss derived from DXA scans.
- To assess the sensitivity and specificity of these biomarkers in predicting loss of SMM.
AS 199 - Summary and Aims
Low relative skeletal muscle mass (SMM) or sarcopenia contributes to the decline in physical functions among the elderly. Both genetic factors and environmental factors may contribute to the development of sarcopenia. However, very little is known about genetic risk factors and their interactions with environment factors in aging-related loss of SMM. The primary objective of this study is to investigate genetic variations in selected catabolic (IL-1, IL-6, TNF-alpha) and anabolic (IGF-1 and GH) factors in relationship to SMM loss among older women. Gene to gene interactions as well as interaction between gene and environmental factors will also be examined. A case-cohort study design will be used to include 800 cases and 2000 sub-cohort of women who are matched on age and ethnicity with the cases and are selected from the entire WHI OS DXA (dual-energy x-ray absorptiometry) cohort. The cases are defined as women with the highest (top 10%) rate of SMM loss during the follow-up. SMM can be estimated from DXA-derived body composition measurements based on previously published studies. The precision of the estimates on SMM will be further improved in an ongoing WHI ancillary study (AS#153, PI: Zhao Chen). Results of this study may help us to identify high-risk populations for sarcopenia and to develop targeted therapies and preventions to reduce SMM loss among the growing population of older people in the United States.
Aims
Our primary objective of this study is to investigate genetic variations and interactions of genetic and environmental factors in determining rate of skeletal muscle loss. Using the resources of the Women’s Health Initiative and the invaluable biospecimen collection and body composition measures (from dual-energy x-ray absorptiometry –DXA) over time, we propose the following primary specific aims:
- To evaluate the role of genetic variation in catabolic inflammatory cytokines (IL-6, IL-1, TNF-alpha) on SMM loss (DXA-derived measurements) in age- and ethnicity-matched postmenopausal women controlling for levels of physical activity.
Data Dictionaries and Study Documentation
This section displays all study-related data dictionaries and study-related files. The investigators for this study will upload the datasets, data dictionaries, and other study-related files. Study-related files will be made available to the public one year after the completion of the ancillary study, with the exception of the datasets, which will only be available to those with a Data Distribution Agreement. Those will be available to those with permission to download and will appear as a download link next to the data dictionary
Data Dictionaries
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Study Documents
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| NameAS191-199 case control selection.pdf | Description |
