Model parameters adjustment. (A) Schematic illustration of the AC-AC-cAMP-PKA signaling cascade. AC is activated by adrenergic receptors (β-AR) and calmodulin and deactivated by cholinergic receptor (ChR) stimulation. Activated AC converts ATP into cAMP, which itself is transformed into PKA. PKA phosphorylates several targets, including PLB proteins, whose phosphorylation level will regulate the activation of SERCA and thus the rate at which Ca²⁺ enters the SR. The model includes two restraining mechanisms that act like brakes: protein phosphatase (PPT), which removes phosphate groups from proteins, and PDE, which breaks the phosphodiester bond in cAMP and degrades its level. (B) I_f shift in the I–V curve as a function of cAMP in adult and aged mice. Basal state (V shift = 0 and [cAMP] = 20 pmol/mg protein). The maximal shift for adult and aged mice was taken from the experimental results of Sharpe et al. (2017). (C) PLBp modulation of SERCA in adult and aged mice. The expressions for adult and aged mice are empirical.