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Human skin enables interaction with diverse materials every day and at all times. The ability to grasp objects, feel textures, and perceive the environment depends on the mechanical behavior, complex structure, and microscale topography of human skin. At the same time, abrasive interactions, such as sometimes occur with prostheses or textiles, can damage the skin and impair its function. Previous theoretical and computational efforts have shown that skin’s surface topography or microrelief is crucial for its tribological behavior. However, current understanding is limited to adult surface profiles and simplified two-dimensional simulations. Yet, the skin has a rich set of features in three dimensions, and the geometry of skin is known to change with aging. Here we create a numerical model of a dynamic indentation test to elucidate the effect of changes in microscale topography with aging on the skin’s response under indentation and sliding contact with a spherical indenter. We create three different microrelief geometries representative of different ages based on experimental reports from the literature. We perform the indentation and sliding steps, and calculate the normal and tangential forces on the indenter as it moves in three distinct directions based on the characteristic skin lines. The model also evaluates the effect of varying the material parameters. Our results show that the microscale topography of the skin in three dimensions, together with the mechanical behavior of the skin layers, lead to distinctive trends on the stress and strain distribution. The major finding is the increasing role of anisotropy which emerges from the geometric changes seen with aging.