Structural Modifications of Proteins During Aging

ging is a fundamental phenomenon that affects somatic A cells whose manifestations, however, may differ from one cell type to another. While most of us possess an intuitive understanding of what aging is, and can tell a young person from an old one, a precise definition of aging and its relationship to development has been surprisingly difficult to develop. The phenomenon of senescence can be defined descriptively as the highly complex ensemble of deteriorative processes that slowly, and irreversibly, increase the susceptibility of an organism to disease and predispose it to death. By emphasizing those processes that lead to a decline in the ability of the organism to cope with environmental stresses, this definition allows one to intuitively, though somewhat arbitrarily, separate aging from development (the latter process installing, and enhancing, an organism’s ability to adapt to its environment and to respond to changes in it). The drawback of this very general definition of aging, however, is that it gives no clue as to the fundamental biological processes that regulate, or are involved in, the aging process and provides no indication of the mechanisms by which these processes manifest themselves. A number of hypotheses to explain the origin of biological aging and to provide more mechanistic insight have been developed and are able to be tested by experiment. These have been described in a number of recent reviews and research publication^.'-^ The aim of the present review is to provide a somewhat more focused description of one aspect of aging, the age-related changes in proteins, thus summarizing the current knowledge of the aging phenomenon at its most elementary level, the molecular level . Proteins are macromolecules that serve to execute, regulate, and mediate nearly all biological functions in the cell as well as in the intercellular matrix. The complexity of life processes requires that hundreds, even thousands, of different proteins be present in a living cell at any given moment, each performing a specific task (a typical example being the catalysis of a single chemical reaction within a sequence of reactions that together carry ou t a biological process). To ensure that only reactions beneficial to the organism occur to any significant extent, proteins need not only be very efficient and specific in their function but must also possess the ability to be regulated by external stimuli (for example by becoming phosphorylated in response to signals from hormones, etc.)