The bone-tooth organ in rats is extensively used as a model system to study the effects of various external perturbations, which include NVP-BEZ235 extraneous loads and disease states. Systematic studies at the cell, tissue, and organ levels continue to be performed on rats because of the limited availability of whole human bone-tooth complexes. Examples include but are not limited to periodontal diseases and load-mediated effects. While younger animal models may still be undergoing the complex processes of development and maturation, those in the senescent phase may already be compromised by age associated diseases. Age-related differences can also be translated into biochemical and physico-chemical changes, critical to accurate interpretation of experimental factors. These changes in part could be due to the varying response of the mechanosensory system and/or hormonal influences, both of which alter the mechanical efficiency of muscle, bone, and their respective interfaces. There is evidence supporting the loss of functional efficiency in a joint with age due to an innate decrease in metabolic rate of cells within mineralized and soft tissues, as well as the soft-hard and hard-hard tissue interfaces. To understand function-related changes, time-related functional adaptation of bone was intelligently delineated as modeling, compared to the innate remodeling of tissues. Modeling dominates in growing rats, where gains in bone formation, strength, and mass were observed due to the dominance of muscle mass in shaping bone as functional units. However, from adulthood, extraneous loads and significant deviations from physiological threshold limits could affect the form or shape of load bearing functional units. Age-related changes in organ biomechanics, were related to the changes in PDL mechanical properties, turnover rate, PDL-width and density, along with increased cementum apposition. However, the common denominator for all developed periodontal tissues is functional load. As a result, the rate of change in functional loads with age can alter the rate of mechanobiological events with age. These mechanobiological events could manifest as biophysical changes within the load bearing bone, cementum and PDL in rats. Markers to identify physico-chemical changes in load bearing tissues include varying distribution and relative contents of inorganic and organic constituents, as well as their resulting mechanical properties. It is well known that across mammalian species, the inorganic constituents in various forms of apatite and organic constituents, such as proteoglycans, other noncollagenous proteins, and collagen, together affect tissue and interface mechanics. Low and high molecular weight glycosaminoglycan contents associated with small and large proteoglycans were observed to decrease with age in the human periodontium, joint JTP-74057 articular discs, bone, and cartilage.