Inflammatory Cytokines and Physical Frailty in Obese Elderly Subjects 

Dennis T Villareal, M.D.,
Assistant Professor, Division of Geriatrics and Nutritional Science 


Project Overview:
The number of obese elderly persons in the United States is rapidly increasing because of an increase in the elderly population and the percentage of elderly persons who are obese. Obesity has important functional implications in elderly persons because it worsens the age-related decline in physical function, which can lead to frailty and loss of independence. In fact obesity may the single greatest cause of disability in elderly persons (1) and is associated with increased rates of nursing home admissions (2). 

Aging is associated with a decrease in skeletal muscle mass (sarcopenia) and an increase in body fat. Disability occurs when the diminished muscle mass is unable to perform normal daily activities. We recently found that most community-living obese elderly persons (age > 65 y, BMI > 30) met our criteria for physical frailty (low scores in the physical performance test, peak endurance power, and functional status questionnaires). Furthermore we found that physical frailty in obese elderly persons was associated with lower skeletal muscle mass and poorer muscle quality (Obes.Research, in review). Moreover, obese elderly persons had lower leg strength, poorer gait and balance (e.g. assessed by walking speed, obstacle course), and poorer quality of life (e.g. assessed by SF-36) compared to nonobese elderly persons. Thus, contrary to common belief, obesity in the elderly does not protect against sarcopenia (but in fact, predisposes to it!), which is associated with physical frailty that leads to loss of independence and premature institutionalization. The mechanism/s for our finding of sarcopenia in obese elderly persons need to be investigated, as these could lead to effective interventions to maintain independence and improve quality of life in the increasing elderly population.

Aging is associated with increase in the circulating levels of proinflammatory cytokines, tumor necrotic factor (TNF)-alpha and interleukin (IL)-6 but elevations are not very marked and levels are much lower than those observed during acute infections (3).

Low-grade inflammatory activity, however, may play a pathogenetic role in several age-associated diseases. Although causal relationships remain to be demonstrated, high plasma levels of TNF-alpha and IL-6 have been associated with insulin resistance, muscle wasting, and high mortality risk in elderly (4,5). The origin of elevated TNF-alpha and IL-6 levels observed during ageing has not been clarified. Many different cell types, particularly adipose tissues, can produce both cytokines. In fact, increased levels of TNF-alpha and IL-6 have been reported in obese subjects and have been associated with visceral adiposity and type 2 
diabetes (6). 

We hypothesize that obesity would be associated with a further increase in the levels of TNF-alpha and IL-6 in the elderly, which in turn would be associated with an exacerbation of the age-related decline in physical function and quality of life. The results of our proposal should stimulate interventions that have the potential to decrease cytokine levels and prevent or slow the decline in physical function and quality of life in obese elderly persons (e.g. weight loss and exercise). They will also provide evidence for the importance of measuring inflammatory cytokines as predictors of physical dysfunction and quality of life in the elderly.

Final Report:
The number of obese elderly persons in the United States is rapidly increasing because of an increase in the elderly population and the percentage of elderly persons who are obese. Obesity has important functional implications in elderly persons because it worsens the age-related decline in physical function, which can lead to frailty and loss of independence. In fact, obesity may the single greatest cause of disability in elderly persons 1 and is associated with increased rates of nursing home admissions. Read the full Final Report.