Academic Appointments

  • Academic Fellow - Law, Stanford Law School

Contact

  • Academic
    slal36@law.stanford.edu
    University - Other Teaching/Research Department: Law Academic Matters Position: Empirical Research Fellow for Prof. Morantz

Additional Info

  • Mail Code: 8610

All Publications

  • Cellular metabolic pathways of aging in dogs: could p53 and SIRT1 be at play? GeroScience Jimenez, A. G., Paul, K. D., Benson, M., Lalwani, S., Cipolli, W. 2023

    Abstract

    Aging and cancer seem to be closely associated, such that cancer is generally considered a disease of the elderly in both humans and dogs. Additionally, cancer is a metabolic shift in itself towards aerobic glycolysis. Larger dog breeds with shorter lifespans, and increased glycolytic cellular metabolic rates, die of cancer more often than smaller breeds. The tumor suppressor p53 factor is a key suppressor oncogene, and the p53 pathway arrests cellular proliferation and prevents DNA mutations from accumulating during cellular stress. The p53 pathway is also associated with the control of cellular metabolism to prevent cellular metabolic shifts common to cancerous phenotypes. SIRT1 deacetylates the p53 tumor suppressor protein, downregulating p53 via effects on stability and activity during stress. Here, we used primary fibroblast cells from small and large puppies and old dogs. Using UV radiation to upregulate the p53 system (100J/m2), control cells and UV-treated cells were used to measure aerobic and glycolytic metabolic rates using a Seahorse XFe96 oxygen flux analyzer. We also quantified p53 expression and SIRT1 concentration in canine primary fibroblasts before and after UV treatment. We demonstrate that, due to a higher p53 nuclear to cytoplasmic ratio in large breed dogs after UV treatment, p53 could have a more regulatory effect on large breed dogs' metabolism compared with smaller breeds. Thus, there may be a link between p53 upregulation and inhibition of glycolysis in large breed dogs during times of cellular stress compared with small breed dogs. However, SIRT1 concentrations decrease with age in domestic dogs of both size classes, suggesting a possible release of inhibition of p53 through the SIRT1 pathway with age. This may lead to increased incidences of cancer, especially due to the more pronounced upregulation of p53 with cellular stress.

    View details for DOI 10.1007/s11357-023-00942-y

    View details for PubMedID 37768524