In one embodiment, the present invention provides methods of modulating the deacetylase activity of SIRT1 in one or more cell by modifying the binding affinity of lamin A to SIRT1 via one or more interaction modifying compound. In another embodiment, the present invention provides methods of screening SIRT1-activating/inhibiting compounds based on the interaction between lamin A and SIRT1 proteins and SIRT1-activating property of lamin A. In another embodiment, the present invention provides uses of SIRT1-activating compounds to treat patient(s) suffering from metabolic and/or aging-related degenerative diseases, and uses of SIRT1-inhibiting compounds to treat human malignancies.