Current Research Projects

1) Mechanisms of Age-Related Loss of Function

In some individuals  the age-related loss of function (whether physical, contractile, cognitive, cardiovascular, or other systems) becomes clinically relevant leading declining quality of life, potential frailty development, onset of dementia or mild cognitive impairment, loss of independence, and increased mortality rates.  To address the search for potential novel mechanisms and therapeutic targets, we have created batteries of preclinical (mouse) tests to assess function over the entire lifespan. We created a composite scoring system, CFAB or comprehensive functional assessment battery, consisting of a battery of well-validated tests including rotarod (overall motor function), treadmill max speed (endurance, aerobic capacity), inverted cling (overall strength/endurance), grip meter (fore-limb strength), and voluntary wheel running (volitional exercise rate) to measure the physical ability and exercise capacity of mice (see our publication PMC8087272 for further details). Furthermore, we use Promethion metabolic cages to determine basal metabolic rate, oxygen consumption, food/water intake, and activity patterns. We test skeletal muscle function using in vivo (plantar flexor and dorsiflexor torque, or quadriceps) and ex vivo (soleus, EDL, and diaphragm force, velocity, and power) contractile physiology (details in our selected publications: PMC11809237 , PMC8095664 , PMC5911410 , PMC6469996 , PMC4401475 , PMC3805297 ). We examine cognitive function  with CAB (Cognitive Assessment Battery, details in our pre-print published at bioRxiv BIORXIV/2025/638126 ; doi: https://doi.org/10.1101/2025.02.14.638126), consisting of the following cognitive tests: open field (anxiety and exploratory behavior), novel object recognition (long-term memory), puzzle box (executive function, and y-maze (short-term and spatial memory), and are currently validating these cognitive tests in a variety of ages of both sexes.  In addition, we also have recently begun measuring cardiovascular health using blood pressure and echocardiographs as outcome measures. We use these multiple tests to assess changes to function in mice over the lifespan in both normal aging and in the context of frailty, sarcopenia, as well as to evaluate the effect of various exercise models (See Project 3 below) to mitigate deleterious changes brought on by aging. Out goal is to eventually identify novel mechanisms that influence age-related changes in tissue that are directly associated with functional decline or preservation. This work is ongoing.

2) Transcriptomic and Proteomic Alterations Associated with Age-Related Functional Decline

This is an active area of ongoing research for the lab. In brief, this research project involves using our CFAB scoring system (described above in Project 1), on different ages (adult, middle-aged, older, and oldest old) to rate functional status and then collecting muscle samples. Using bulk RNAseq, we examine 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 oldest-old  (28+ month old) mice there were over 6500  differentially expressed genes (DEGs) with age (multiple-comparisons adjusted p-value, adj pval, <0.05). When we curate to examine only  gene expression changes of log2 fold change of 1 or greater and multiple comparison adjusted p-values < 0.05, there were 638 DEGs that were at least moderately correlated (R>0.50) with function as measured by CFAB, with 273 strongly correlated (R>0.70) (see our publication PMC10597580 for more details). We will expand our examination to proteomics (tandem mass spectrometry, lc-ms/ms), metabolomics (see our publication PMC10739780 for details) and to investigate the effect of exercise to modulate age-related changes associated with functional decline (see Project 3 below. This work is ongoing, with future investigations to include brain and cognitive function.

3) Intersection of Aging, Function, and Exercise

In this research project we are learning how  exercise affects function, the transcriptome and the proteome differentially in older, middle-aged, and adult mice. We currently are using high intensity interval training (HIIT) and voluntary wheel running (VWR) as exercise models (see our publications PMC10958787  and  PMC4553716 for details), but will expand to moderate intensity continuous training, high intensity functional training (HIFT, essentially HIIT with weights–see our publication PMC6544743 for details). We include control mice do not exercise but have a sham treatment (important for cognitive assessment). We assess CFAB and CAB before and after the training in all mice and then compare the effect of training on function (cognitive, physical, contractile) and frailty/sarcopenia onset. We will determine the effect of exercise not just on physical/cognitive 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), metabolism (e.g., metabolic cages, mitochondrial function), and many other outcome measures. This work is ongoing.