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"Metabolic Signatures of Unintentional Body Weight Loss and Health Conditions in Community-Dwelling Older Adults", Epidemiology/Public Health. 

Committee 

  • Anne B. Newman, Department of Epidemiology (dissertation advisor) 
  • Iva Miljkovic, Department of Epidemiology 
  • George C. Tseng, Department of Biostatistics 
  • Samaneh Farsijani, Department of Epidemiology 
  • Ventakesh L. Murthy, DIvision of Cardiovascular Medicine, University of Michigan 

Abstract

Unintentional weight loss is common in older populations and is related to underlying disease and higher mortality risks. Metabolomics, the comprehensive assessment of metabolic molecules, can reveal metabolic pathways underlying unintentional weight loss and help identify older adults at risk, informing early prediction and intervention strategies. Among the Health, Aging and Body Composition study participants, I aimed to 1) identify metabolites and pathways associated with incident 2-year unintentional weight loss, 2) determine metabolites and pathways associated with 5-year unintentional weight loss and their relationship with body composition (i.e. muscle, fat, and bone mass) changes, and 3) develop a metabolite composite score to explain unintentional weight loss-related mortality and mobility limitation risks. For Aim 1, I found that lower levels of lipids (e.g. long-chain unsaturated triglycerides, phospholipids) and amino acids (e.g. branched-chain amino acids and aromatic amino acids), and higher sugar levels were related to subsequent unintentional weight loss. These associations were partly explained by predisposing factors such as low muscle mass, poor appetite, and diabetes. In Aim 2, I observed similar metabolic profiles for 5-year unintentional weight loss as for 2-year unintentional weight loss. Loss of fat mass loss and muscle mass significantly influenced these metabolite correlates. In Aim 3, I developed a metabolite score comprising 27 unintentional weight loss related metabolites, which was associated with unhealthy diet, physical inactivity, low muscle mass, impaired kidney function, and poor glucose regulation. The score significantly predicted all-cause mortality and mobility limitation in older adults with and without weight loss. The score also explained 39% and 27% of the elevated mortality and mobility limitation risks related to unintentional weight loss. The metabolic profiles of unintentional weight loss suggested critical roles of mitochondrial dysfunction and inflammation in unintentional weight and muscle loss. These pathways might be related to unhealthy diet, physical inactivity, and uncontrolled kidney or glucose disorders. This knowledge has important public health implications because it informs potential intervention point (e.g. mitochondrial health) and strategies (e.g. dietary and exercise interventions, stabilizing kidney function and glucose levels) to prevent unwanted weight and muscle loss, promote healthy aging and preserve independence in later life.

Event Details

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https://pitt.zoom.us/j/94176733690

Meeting ID: 941 7673 3690

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