Search bioRxiv⌕ Search

Biology subjects

Pajski, M. L.

Publications and source records attributed to Pajski, M. L..

2 recordsLinked to original sources

Endurance Exercise to Improve Physical Function in Adult and Older Mice: High Intensity Interval Training (HIIT) versus Voluntary Wheel Running (VWR)

With age comes a gradual decline in physical function and exercise capacity, concurrent with a progressive propensity for development of sarcopenia /(age-related loss of muscle mass and strength) and frailty (inability of body to thrive and maintain homeostasis). Prior research has demonstrated that exercise, while not a cure, can help mitigate sarcopenia/frailty and restore functional capacity. Reliable, validated, pre-clinical models are necessary to elucidate the underlying molecular mechanisms at the intersection of age, exercise, and functional decline. In this study, we hypothesized that endurance exercise programs mimicking typical human exercise protocols would improve physical function in both adult and older adult mice. Furthermore, our secondary hypothesis was that older mice would receive less benefit from a similar volume of exercise than adult mice. To test these hypotheses, we randomly assigned (with some selection criteria) male C57BL/6 mice either at adult ages during the study (n=24, designated 10m, aged 6 months to 10 months) or at older adult ages (n=18, designated 26m, aged 22 months to 26 months) to a 13-week program of voluntary wheel running (VWR, group termed RUN) or high intensity interval training (HIIT), with an additional 10m sedentary control (CON). The functional aptitude of each mouse was determined pre- and post-training using our composite CFAB (comprehensive functional assessment battery) scoring system consisting of voluntary wheel running (volitional exercise and activity rate), treadmill (endurance), rotarod (overall motor function), grip meter (forelimb strength), and inverted cling (whole body strength/endurance). To measure sarcopenia, we tracked body mass and body composition changes with EchoMRI, and measured muscle wet mass post-training.

physiology↗

Skeletal Muscle Transcriptome Alterations Related to Physical Function Decline in Older Mice

One inevitable consequence of aging is the gradual deterioration of physical function and exercise capacity, driven in part by the adverse effect of age on muscle tissue. Our primary purpose was to determine the relationship between patterns of gene expression in skeletal muscle and this loss of physical function. We hypothesized that some genes changing expression with age would correlate with functional decline, or conversely with preservation of function. Male C57BL/6 mice (6-months old, 6m, 24-months, 24m, and 28+-months, 28m; all n=8) were tested for physical ability using a comprehensive functional assessment battery (CFAB). CFAB is a composite scoring system comprised of five functional tests: rotarod (overall motor function), grip strength (fore-limb strength), inverted cling (4-limb strength/endurance), voluntary wheel running (activity rate/volitional exercise), and treadmill (endurance). We then extracted total RNA from the tibialis anterior muscle, analyzed with Next Generation Sequencing RNAseq to determine differential gene expression during aging, and compared these changes to physical function. Aging resulted in gene expression differences >[boxv]1.0[boxv] log2 fold change (multiple comparison adjusted p<0.05) in 219 genes in the 24m and in 6587 genes in the 28m. Linear regression with CFAB determined 253 differentially expressed genes strongly associated (R>0.70) with functional status in the 28m, and 22 genes in the 24m. We conclude that specific age-related transcriptomic changes are associated with declines in physical function, providing mechanistic clues. Future work will establish the underlying cellular mechanisms and the physiological relevance of these genes to age-related loss of physical function. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/444371v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@ad7362org.highwire.dtl.DTLVardef@17267e7org.highwire.dtl.DTLVardef@38600org.highwire.dtl.DTLVardef@15283a7_HPS_FORMAT_FIGEXP M_FIG C_FIG RNA sequencing of skeletal muscle from young and old mice were compared to physical function status obtained by performing a comprehensive functional assessment battery of tests. Between adulthood (6-months) and older age (28-months), 6707 genes were differentially expressed with 253 of these genes being significantly associated with physical function. Specific age-related changes to the skeletal muscle transcriptome are associated with a decline in physical function.

physiology↗