Studies Using Aged Animals

Biological aging is emerging as a therapeutic target and multiple diseases are associated with aging including dementia, cardiovascular disease, diabetes, bone and joint issues etc. To develop therapies targeting age-related diseases, it is essential to perform studies in aged rats and mice as these models display the hallmarks of aging. However, it is cost-prohibitive and time consuming to develop a cohort of aged animals de novo.

At Charles River, our scientists conduct contract studies in aged animals (rats and mice) to study cognitive decline and other studies associated with aging including Alzheimer’s disease research and dementia. These studies can be customized to test the efficacy of novel therapeutics. Aged cohorts of animals are immediately available to start studies in a short timeframe.

Our aged rat and mouse models begin to exhibit cognitive, biochemical and brain metabolism deficits at approximately 19-20 months of age. Aged rat and mouse studies can also be combined with scopolamine-induced amnesia studies. A typical study design is shown below.

Study Design

example study paradigm of rat and mice models of aging and cognitive decline
Neurological Findings in Aged Rats Using Translational Imaging Technologies: PET, SPECT and MRI

Image of the scientific poster Neurological Findings in Aged Rats Using Translational Imaging Technologies: PET, SPECT and MRIIn this poster, scientists examined the neurological changes caused by aging, including minor impairment in memory and cognition with translational imaging techniques.

Download the Poster

Study Endpoints

Physiological endpoints:

Biomarkers:

  • PET imaging, SPECT imaging and MRI to study changes in cerebral blood flow, neuroinflammation and blood brain barrier changes.
  • Synaptophysin mRNA (qPCR) and protein(IHC/WB) levels
  • Changes in bioenergetics, mitochondrial and redox readouts
    • 31P-MR spectroscopy to measure bioenergetic readouts including ATP, ADP, PCR, Pi
    • 1H-MR spectroscopy to measure hippocampal metabolic profiling (PCR, CR, NAA, TAU, GLU, GLN, LAC, GABA, mINS, ACE, CHO and GSH)
  • Neurochemical measurement using HPLC for ACh, DA, 5HT, NE
  • Cell Population and Proliferation
    • Immunohistochemistry (IHC) for NeuN, GFAP and Iba-1
    • BrdU incorporation

 

Prolonged latency in aged animals compared to young animals showing memory loss and cognitive decline in the aged animal group.

Line graphs showing increased latency (ie. time to find platform in Morris water maze test) in aged animals (blue line) compared to young animals (green line).

 

Reduction in PSD95 levels in older compared to younger animals. PSD95 is known to be reduced in aged animals.

Bar graph showing reduced levels of PSD95 mRNA measured by quantitative PCR (qPCR) in aged animals (green bar) compared to young animals (blue bar).

 

 

Measurement of various neurometabolites in aged animals and young animals using proton magnetic resonance spectroscopy. Asterisks mark statistically significant differences in specific metabolites between the two cohorts.

Bar graphs showing differences in brain metabolites between young (blue bars) and aged animals (green bars). Asterisks mark statistically significant differences in specific metabolites between young and aged animals.