Analyzing feed-forward loop relationship in aging phenotypes: Physical activity and physical performance

Abstract: We present evidence of feed-forward loop relationships and positive association between physical activity and performance levels, which are components of frailty, using measures from 431 high functioning women initially aged 70–79 years followed over 7 visits. Physical activity levels were assessed using a questionnaire. Grip strength was measured using a handheld dynamometer and usual walking speed was measured over 4-m. The results suggest that a reduction in physical activity would not only degrade physical performance, but it would further reduce physical activity through declines in physical performance. As both physical activity and physical performance impact frailty, improvement of physical activity could help reduce frailty directly as well as indirectly via improved physical performance. Our findings support a priori hypothesis that feed-forward loops are present in the phenotype of frailty, which is due to dysregulated energetics. A methodologically broader implication is that we introduce modeling and analysis of feed-forward loop data here. The feed-forward loop, as we define it, is different from the concept of feedback loops used in biochemical systems. Generalizing our model of two-variable feed-forward loop, three, four or multivariable feed-forward loop can be applied to other biological systems.


Alex’s Notes: The present study focuses on frailty in older adults – defined as three of the following being present: shrinking, weakness, poor endurance, slowness, and physical inactivity – but does so with a very interesting and unique multisystem model. The authors utilize a “feed-forward loop,” which they define as a phenomenon where a variable is able to indirectly influence itself through other variables. An excellent example of this would be exercise and endorphins. When you exercise, you feel good, which in turn makes you want to exercise, which makes you feel better, which results in a continuous loop forward where exercise perpetuates itself by making you feel good.

This feed-forward loop is a novel concept that would let future research see how multiple systems jointly affect each other and themselves. This system needs testing, however, and the authors decided to frailty in older adults and test for evidence of intercommunication between physical activity and performance levels (grip strength & walking speed) among 431 women aged 70–79 who participated in the Women's Health and Aging Study II (WHAS II) and had walking speed, grip strength, or physical activity measures over seven visits.

The data used in the study came from the hyperlinked studies above. Briefly, the women were representative of the two-thirds highest functioning women living in the community, and had either no difficulty or difficulty in only one of the following tasks: mobility, upper extremity, household management tasks, and self-care tasks.Interviews and physical examinations were conducted at baseline and at 6 follow-up visits (approximately 18 months apart except for the interval between the third and the fourth visit, which was, on average, 3 years), for a median follow-up of 12 years (between 1994 and 2009).Physical activity level was assessed using a shortened version of the Minnesota Leisure Time Activities Questionnaire, which includes four exercise activities (walking for exercise, dancing, bowling, and strengthening activities) and two lifestyle activities (strenuous household and outdoor activities), and performance levels were assessed as grip strength and walking speed.

The researchers then did a bunch of fancy math stuff to formulate their feed-forward loop equation, and did indeed find that physical activity and performance has a complex loop structure in which these two variables are positively associated with each other.The strongest feed-forward loop relationship was between various measures of physical activity (physical activity min/week, energy spent kcal/week, kcal/day-kg and energy spent in lifestyle activities kcal/week) and walking speed.

“Thus, a reduction in physical activity would not only degrade physical performance, but it would further reduce physical activity through declines in physical performance. If there are other mediating variables between physical activity and physical performance (e.g. muscle strength and/or hormones), deterioration in either of physical activity and physical performance will also worsen the mediators. For example, if muscle strength is a mediators between physical activity and physical performance (i.e. physical inactivity decreases muscle strength, which in turn decreases physical performance, e.g. walking speed), then deterioration in either of physical activity and physical performance will decrease muscle strength as well.”

No doubt these results are inspiring and provide a stepping stone for future research to uncover more intimate relationships between physical activity, muscle mass, muscle strength, inflammation, and overall health.

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