We propose to add the measurement of muscle mass to an already funded program project
grant. Rapid declines in physical functioning often occur after the diagnosis of cancer,
especially among older cancer survivors; however, a handful of diet and exercise interventions
have been found to ameliorate these losses. The contribution of muscle mass and changes in
muscle mass in older men and women, particularly those who have survived cancer is not well
characterized, partly due to the inability to directly and accurately quantify skeletal muscle mass
and reliance on assessments of lean mass as a surrogate. The Adapting MultiPLe behavior
Interventions that eFfectively Improve (AMPLIFI) Cancer Survivor Health (1P01CA22997)
is aimed at testing three distinct lifestyle interventions among 652 older, inactive, overweight or
obese cancer survivors, a large proportion of whom will be minority and rural. The interventions
include: 1) a 6-month dietary intervention aimed at improving diet quality and weight loss, as
well as preserving lean body mass; 2) a 6-month intervention that is aimed at promoting
aerobic physical activity; and 3) a 12-month diet and exercise intervention that combines both
diet and exercise simultaneously (and effects will be evaluated against the combination of
interventions 1 and 2 in sequence). Visiting nurses will assess physical function and perform
phlebotomy at home health assessments scheduled at baseline and every six months;
participants also will complete surveys that assess diet, physical activity and overall quality of
life. We propose to measure the effects of these interventions on muscle mass using
the novel D3-creatine (D3Cr) dilution method. We have demonstrated that this non-
invasive method can be implemented in a large cohort study (MrOS) and that D3Cr muscle
mass is strongly associated with functional capacity and risk of disability and that age-
associated decreases in muscle mass are associated with slower gait speed and decreased
strength. These associations were not observed using DXA derived lean mass. Subjects will
ingest a 60 mg capsule of D3Cr and produce a fasting urine sample 48 – 96 hours later for
the assessment of D3-Creatinine enrichment to determine creatine pool size and, because
98% of total body creatine is found in muscle, muscle mass. For the first time, the
relationship between changes in muscle mass resulting from exercise and weight loss and
functional capacity and physical activity will be assessed in this at-risk population of older
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