Aging represents the accumulation of changes over time and generally increases the risk of a wide range of disease. Compounds that target the aging process may therefore have broad therapeutic applications.
Aging is a complex process in which all tissues in the body change over time. Given the multitude of potential causes of aging, it is challenging to find a good model system for this process. The most holistic, agnostic, and straightforward method is to let wild-type mice age naturally over time. At Sylics, we have access to aged cohorts of C57BL/6J (B6) mice up to 2 years of age. By 22 months of age, B6 mice display profound changes in behavior, different from changes seen in neurodegeneration models, such as decreased activity and velocity in the PhenoTyper.
Aged tissues progressively accumulate senescent cells. These cells play causal roles in age-related pathologies, likely mediated through their secretion of proinflammatory molecules. Essentially all cells in the nervous system express markers of cellular senescence during aging and neurodegeneration-related pathologies.
Sylics performs experiments in mouse models with pathologies shown to be associated with upregulation of senescence markers, such as models of Aβ plaque pathology, tau pathology, and natural aging. Histological staining for p16 (i.e. p16INK4A) and β-gal (β-galactosidase) is used to assess senescence.
EIF2B mutant mice
The transcription factor eIF2B modulates protein homeostasis via regular of stress response pathways. Dysregulated protein homeostasis is a hallmark of aging and eIF2B was shown in several studies to promote longevity through inhibition of the integrated stress response (ISR).
Sylics offers services with a unique mouse model with dysfunctional eIF2B signaling, which leads to Vanishing White Matter disease. These mice have a dysfunctional ISR, which makes them an attractive model to test compounds that promote longevity through this pathway.
Please reach out to us if you want to learn more about our Aging solutions. We will contact you within 1 business day.