Aged Mouse Cells

There have been numerous reports of senescence at sites of aging pathology, but whether they cause disease or are consequence of pathology is unclear. In some cases, loss of proliferation-competent cells may be responsible for pathological changes, such as in glaucoma, cataracts, the diabetic pancreas and osteoarthritis. These results lead us to propose models of the interrelationship between chronic aging and disease risk to guide further inquiry into the states of these diseases.

Age-Associated Changes in Alveolar Epithelial Cell (AEC) Functions

A study reports that nasal epithelial tissue from aged subjects without respiratory disease shows a significant decrease in microtubular disarrangements and ciliary beat frequency. Ageing also reduces the clearance of Teflon particles in small airways of the elderly. In addition, mucus secretion from AECs is also affected with age. Mucus secretion, as measured by periodic acid-schiff (PAS) staining and mRNA expression of mucin-5 subtype A and C (MUC-5AC), was found to be increased in older mice challenged with ovalbumin in trachea.

Changes in age-related lung extracellular matrix components have also been reported to affect the function of AECs. In a study of patients with chronic sinusitis, age-associated reduction of S100A8/9 proteins was observed in the elderly. S100A8/9 proteins or calprotectin are produced during infection and act as chemoattractants for neutrophils and monocytes. Take together, these studies suggest that AEC function is significantly affected by age and thus may play an important role in age-associated chronic respiratory diseases.

Age-Associated Changes in Dermal Fibroblast Functions

Age-related changes and environmental stresses affect all the cellular elements in the skin, but changes in stromal fibroblasts are particularly important because they maintain the connective tissue of the skin.

Skin damage is a result of the chronological aging process. The effects of excessive sun-expose (photo-aging) and other environmental stresses are superimposed on the harmful changes that occur as a result of aging. Chronological aging coupled with environmental stresses cause changes in connective tissue-synthesizing cells, leading to increased destruction of collagen and reduced ability to replace damaged collagen. Based on the above information, we can see that the inherent age-related changes in fibroblast function in conjunction with environmental stresses bring about connective tissue damage, which in turn, further impairs cell function. The result is a vicious circle that, if not checked, will end with the cosmetic and medical consequences. Thus, elucidating the cellular and molecular mechanisms that underlie alterations in fibroblast function may find ways to prevent or slow down skin aging.

Age-Associated Vascular Endothelial Dysfunction

The endothelium is a dynamic, heterogeneous, dispersed organ with vital secretory, synthetic, metabolic and immunologic functions. Vascular endothelial cells (EC) are a large number of quiescent cells in the inner wall of blood vessels. In vitro, EC have a finite number of cell replication reaching replicative senescence. This cessation of cell division is accompanied by a series of changes in cell function, morphology and gene expression that may contribute to age-associated diseases including atherosclerosis. Interestingly, vascular endothelial cells with age-related phenotypes have been detected in the atherosclerotic regions of human aorta and coronary arteries. EC senescence is partly regulated by the inflammatory cytokine interleukin 1α (IL-1α), which is expressed in human atherosclerotic vessels and mainly in the endothelium. It is noteworthy that EC replicative senescence is associated with atherosclerosis.

Age-Associated Vascular Smooth Muscle Cell Growth Kinetics

Age is a risk factor for atherosclerosis. The vascular smooth muscle cell (SMC) proliferation, an integral part of atherosclerotic plaque formation, was measured by comparing the growth kinetics of SMC in aged and young adult mice. The results showed that old animals exhibiting greater numbers of intimal SMC than younger animals. With the increase of age, SMC responds differently to injury, which indicates that aging produces a change in the vascular SMC that enhances proliferation. This change in response implies that the growth of atherosclerotic plaques is more pronounced with age, which may be due to an agerelated increase in response to the injury rather than merely the accumulation of time-related intimal change.

From a cellular point of view, atherosclerosis is a proliferative process. Because the major cell in the progressive phase of atherosclerosis is SMC, which may also be the source of the extracellular connective tissue in the plaque, so the growth kinetics of these cells as a function of age is of importance for understanding the pathogenesis of atherosclerosis. The differences in the proliferative response of SMCs to endothelial injury with advancing age may partially account for the increased risk of symptomatic atherosclerosis lesions in the elderly.