Septuple columnar stacks of large aromatic molecules with solubilizing side chains have been synthesized via one-step multicomponent self-assembly. At increased concentrations in aqueous solution, m x n aggregates of aromatic stacks form. The simple addition of water induces lyotropic liquid-crystalline mesophases.
Homozygous mutant klotho (KL(-/-)) mice exhibit various characteristics resembling those of human aging, including emphysema. However, age-related changes of lungs have not been fully elucidated. Here, we investigated the structural, functional, biochemical, and cell kinetic alterations of lungs in KL(-/-) mice at 2-12 weeks of age. Homogeneous airspace enlargement and decreased lung elastic recoil were observed in KL(-/-) mice with aging. The apoptotic cells in airway walls in KL(-/-) mice were approximately 6 times greater than those in wild-type (KL(+/+)) mice at 2 weeks of age. However, lipid peroxidation and elastase activity of lungs were not increased in KL(-/-) mice. Western blotting suggested that protein levels of epidermal growth factor (EGF) and phosphorylated extracellular signal-regulated kinase were decreased in KL(-/-) mice. These data suggest that significantly increased apoptosis of airway cells via inhibition of the EGF-dependent pathway may be involved in the development of the aging lungs in KL(-/-) mice.
The great jurist Oliver Wendell Holmes stated: ''I would not give a fig for simplicity this side of complexity, but I would give my life for simplicity on the other side of complexity.'' As geriatricians, we have understandably become aficionados of late-life complexity, although if it is our goal one day to have a truly transformational effect on the major causes of disability in our frail patients, we too must look for hints of simplicity beyond complexity. In this context, we agree with Drs. Rockwood and Mitnitski that an A or A1 grade for our field is premature and should await our or our successors' ability to accomplish the second half of Oliver Wendell Holmes' most insightful statement.
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