In the present chapter, we describe our own attempts to improve our understanding of the pathophysiology of memory in aging. First, we tried to improve animal models of memory degradations occurring in aging, and develop common behavioral tools between mice and humans. Second, we began to use these behavioral tools to identify the molecular/intracellular changes occurring within the integrate network of memory systems in order to bridge the gap between the molecular and system level of analysis. The chapter is divided into three parts (i) modeling aging-related degradation in declarative memory (DM) in mice, (ii) assessing the main components of working memory (WM) with a common radial-maze task in mice and humans and (iii) studying the role of the retinoid cellular signaling path in aging-related changes in memory systems.