Cold‐associated tissue‐specific structural remodeling: A fractal assessment of biological age

Aging is characterized by a progressive loss of physiological complexity. In order to elucidate differences in aging manifestations throughout various tissues/organs, we investigated structural remodeling in interscapular brown adipose tissue (iBAT), gonadal and retroperitoneal white adipose tissues (WATs), and the liver of rats (3-, 6-, and 24-month-old) housed at 22 ± 1°C. An additional cohort of 24-month-old rats housed at 4 ± 1°C from 6 to 24 months of age was used to assess acclimation-driven structural responses. Fractal analysis was employed to quantify parenchymal complexity (via fractal dimension) and heterogeneity (via lacunarity) in iBAT and the liver. Morphometric analyses included measurements of relative tissue mass (for all tissues), nucleus count (for iBAT and liver), and adipocyte diameter (for WATs). Our results revealed distinct patterns of tissue remodeling. Chronological aging was associated with reduced parenchymal complexity in iBAT. The liver exhibited reduced complexity and mass, but its heterogeneity remained stable, whereas WATs underwent hypertrophy. Conversely, chronic cold exposure in aged iBAT was associated with hypertrophy and hyperplasia, underpinned by reduced heterogeneity and increased complexity that positively correlated with cellularity. Moreover, cold exposure led to the depletion of aged WATs, while the liver underwent hypertrophy and regained complexity. Taken together, these results demonstrate the ability of the applied methodology to distinguish the structural changes of chronological aging from those observed following cold exposure. They also validate fractal analysis coupled with morphometry to quantify subtle structural changes associated with early stages of aging, thereby providing a foundation for assessing biological age at the tissue level.