The functional decline that usually accompanies adult aging also encompasses cellular changes including cytoplasmic architecture. In addition to their role in cytoskeletal structure, actin microfilaments have important roles in various cellular processes, including cell-to-cell communication and intracellular signaling. Age-related diseases and late-stage cellular morphological appearances often correlate with altered f-actin structure, which has been observed most notably in cancer. What remains less clear are the molecular pathways that may be involved in normal and premature aging-induced f-actin changes. We report herein that p49/STRAP, a serum response factor binding protein (SRFBP1), is increased with normal aging and appears to be sensitive to low glucose-exposure. Our study results suggest that increased levels of p49/STRAP expression tend to correlate with f-actin redistribution genes, particularly cofilin, while siRNA-mediated knockdown of p49/STRAP resulted in a reduction of thymosin-β4. Furthermore, with the redistribution of f-actin, we observed an increase in the intermediate filament vimentin, compatible with the notion that vimentin may be increased due to its greater role in cytoskeletal dynamics during advancing population doubling levels (PDLs) and in response to a low-glucose exposure. Taken together, these data suggest that p49/STRAP may play a role in glucose-deprivation associated cytoskeletal changes.