Correspondence of large-scale functional brain network decline across aging mice and humans.

Mouse resting-state functional connectivity recapitulates known functional circuits, demonstrating organizational validity of these signals.

• Data were acquired cross-sectionally and longitudinally in awake mice over a broad range of adulthood (n = 82; 3 to 20 months).
• Resting-state fMRI was used to characterize the mouse functional connectome.
• The study confirmed that mouse functional connectivity reflects known functional circuits, validating the use of these signals for network analysis.

Mice exhibit modular architectures of functional brain network organization.

• Graph theoretic analysis was applied to functional connectivity data.
• Modular network architecture was identified in mouse resting-state functional connectivity.
• This modularity is analogous to the large-scale functional network organization observed in humans.

Increasing age in mice is associated with decreasing system segregation, indicative of functional network dedifferentiation analogous to observations in humans.

• Mouse sample spanned 3 to 20 months of age (n = 82), with both cross-sectional and longitudinal data collected.
• System segregation, a graph theoretic measure derived from functional connectivity, decreased with advancing age.
• This pattern of network dedifferentiation mirrors age-related changes previously documented in human aging studies.

Mouse resting-state brain networks are more segregated than those of humans.

• Human data were drawn from the Human Connectome Project and its developmental- and aging-counterparts (n = 1,179; 18 to 90 years).
• Higher segregation in mice was attributable to mice exhibiting a diminished contribution of long-range functional relationships that integrate distributed systems.
• The species difference in segregation level was assessed by directly comparing graph theoretic measures across species.

Mice exhibit slower rates of age-related decline in brain network organization relative to humans.

• Trajectories of brain network aging were compared across mice (3 to 20 months) and humans (18 to 90 years).
• Despite showing qualitatively similar patterns of network dedifferentiation, the rate of decline in system segregation was slower in mice than in humans.
• This finding highlights important species differences in functional brain network aging trajectories.

The diminished contribution of long-range functional relationships in mice accounts for their higher network segregation compared to humans.

• Long-range functional connectivity that integrates distributed brain systems is less prominent in mice than in humans.
• This structural-functional difference underlies the species difference in system segregation levels.
• The finding provides a mechanistic explanation linking spatial scale of functional connectivity to network organization differences across species.

The study establishes a translational model of large-scale functional brain network aging in mice that bridges findings across species and spatial scales.

• The mouse model of functional connectome aging was validated against human aging data from n = 1,179 participants aged 18 to 90 years.
• Both cross-sectional and longitudinal mouse data (n = 82; 3 to 20 months) were used to characterize aging trajectories.
• The authors describe the findings as providing 'a translational bridge across species and spatial scales of analysis,' connecting molecular/cellular mouse models to human brain network aging research.