Current Research Projects
1) Comprehensive Functional Assessment Battery (CFAB):
In brief, this research project involved creating a composite scoring system, CFAB or comprehensive functional assessment battery, of a number of functional tests (including rotarod, treadmill, inverted cling, grip test, and variable wheel running) to rate the physical ability and exercise capacity of male mice of three different ages (adult, older, and elderly). We use this system in our current projects and are looking to expand CFAB to evaluate female mice, and then develop a cognitive aptitude battery using a similar methodology.
The first manuscript from this project (Graber TG, Maroto R, Fry CS, Brightwell CR, Rasmussen BB. (2020) Measuring Exercise Capacity and Physical Function Assessment in Adult and Older Mice.) and three abstracts [Graber TG, Fry CS, Marota Rosario, Rasmussen BB. (2019). Exercise Capacity and Physical Function in Older Mice. Pathobiol Aging Age Relat Dis. 2019; 9(Suppl 1): 1591258, Graber TG, Fry CS, Maroto Rosario, Rasmussen BB. (2018). CFAB: Comprehensive Functional Assessment Battery for Older Mice. Innovation in Aging 2(Suppl 1): 879, and Graber TG, Fry CS, Rasmussen BB. (2018). Comprehensive Evaluation of Physical Function in Older Mice. GeroScience (2018) 40: 405. https://doi.org/10.1007/s11357-018-0041-z] have been published. Parts of this work have been presented at numerous conferences.
2) Transcriptomic Alterations Associated with Age-Related Functional Decline:
This is an active area of ongoing research for the lab and we presented some of our findings at the 2019 Gerontological Society of America annual scientific meeting in Austin, Texas (abstract is published: Graber TG, Marota R, Thompson J, Widen S, Rasmussen BB. (2019) Transcriptome Alterations Associated with Age-Related Decline in Physical Function. Innovation in Aging Vol. 3, No. S1). In brief, this research project involves using our CFAB scoring system (described above in Project 1), on three different ages (adult, older, and elderly) to rate functional status and then collecting muscle samples. Using RNAseq, we are examining age-related transcriptomic changes in skeletal muscle that highly correlate with functional status. As you might imagine, this has generated a lot of data to sift through. For example, in the comparison of the adult (6-month old) and elderly (28+ month old) there were over 6500 genes differentially expressed with age. When we looked only at gene expression changes of log2 fold change of 1 or greater and multiple comparison adjusted p-values < 0.05, there were 638 genes that were at least moderately correlated (R>0.50) with function as measured by CFAB. We are currently expanding our examination to look at all differentially expressed genes between the age-groups, and working to determine their physiological relevance. This work is ongoing. Our first manuscript from this work is in preparation currently.
3) Endurance Exercise to Improve Physical Function in Adult and Older Mice
In this research project we are learning how endurance exercise affects physical function, the transcriptome and the proteome differentially in older, middle-aged, and adult mice. The mice in the exercise groups will be randomized into one of two different endurance training modalities (high intensity interval training and voluntary wheel running). The control mice do not exercise. We assess CFAB before and after the training in all mice and then compare the effect of training on function, frailty and sarcopenia onset. We will determine the effect of exercise not just on physical function, but also on gene expression (using Next Generation Sequencing RNAseq and q-rt-PCR), protein expression and cell signaling (tandem mass spectrometry and Western Immunoblotting), muscle contractile physiology (ex vivo and in vivo), body composition (echoMRI), and many other outcome measures.