Interaction densities depend on size and connectivity of age groups. Interaction densities depend on age group sizes: the connectivity between age groups is normalized by the maximum possible connectivity: the number of connections if all members from the age groups would be interacting. This density is then again normalized by the interaction density of the entire network to allow for comparison between networks of different edges densities (see Materials and Methods for more detail). Age groups that are small and/or have low general connectivity will have low interaction densities with any age group. Interaction densities thus do not only represent a relative connectivity between a pair of age groups (or within one age group), it also reflects the overall connectivity as well as the size for each individual age group. A. Relative size for each age group in the LC network: the proportion of nodes that belong to this age group. The grey line denotes the relative size if all age groups would be of the same size. ABE and Fu are the largest groups. N is the group of proteins that are not assigned to an eggNOG family. B. Relative connectivity for each age group in the LC network, calculated as follows: log2 (avg(degreeage group) / avg(degreenetwork)). The grey line denotes the relative connectivity if it would have been the same for all age groups. Age groups ABE and Fu have a relatively low degree. N is the group of proteins that are not assigned to an eggNOG family. C. Interaction densities between age groups in the LC network: age groups ABE and Fu have in general low interaction densities with each age group reflecting their large size and low connectivity rather than a specific relation between two age groups. D. An improved method of calculating interaction densities: connectivity normalized by expected connectivity (see Materials and Methods for more detail). These densities are independent of the age groups sizes or degree and represent only a specific property of a pair of age groups. Our alternative measure ΔDnew is calculated based on these interaction densities.