Abstract
Sirtuin type 1 (SIRT1), a NAD+-dependent histone deacetylases, plays a critical role in cellular senescence, aging and
longevity. In general, SIRT1 is localized in nucleus and is believed as a nuclear protein. Though overexpression of
SIRT1 delays senescence, SIRT1-protein levels decline naturally in thymus and heart during aging. In the present
studies, we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green
monkey SV40-transformed kidney fibroblast cells (COS-7). Using
SIRT1-EGFP fluorescence reporter, we found that
SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor
deprivation, and we found that SIRT1 partially translocated to cytosol under the treatment, suggesting a reduced level of
SIRT1's activity. We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation,
because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together,
we demonstrated that growth factor deprivation induces cytosolic translocation of SIRT1, which suggesting a possible
connection between cytoplasm-localized SIRT1 and the aging process.
