Age-related cardiac remodeling is characterized by changes in myocardial structure, which include fibrosis (ie, increased collagen concentration). The pathogenetic mechanisms of age-related cardiac changes and possible pharmacologic interventions are still a matter of investigation. A morphometric analysis of collagen accumulation was performed in Sirius Red-stained left ventricular sections of 3-month-old and 5-6-year-old animals after a 9-month period of propionyl-L-camitine treatment (PLC; 120 mg Kg(-1) day(-1) per os); aged rabbits showed decreased interstitial collagen accumulation and no changes in cellularity and apoptotic rate compared to controls. Age-related expression of vascular cell adhesion molecule-1 (VCAM-1)-positive microvessels was also reduced in PLC-treated rabbits. In vitro, the 16-hour, 10-mu M PLC treatment reduced collagen type I and VCAM-1 transcripts, which were investigated by reverse transcription-polymerase chain reaction, more markedly in cardiac fibroblasts from aged donors. In the latter, the anti-VCAM- 1 antibody treatment was found to be associated with a reduction in collagen type I transcripts. Our results demonstrated that long-term PLC treatment partially prevents age-related interstitial remodeling and suggests that a more complex interstitial cell-to-cell signaling regulates senescent myocardium properties.