Link between aging and the nucleolus (original) (raw)

1. Leonard Guarente1
2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 USA

Our ancient ancesters recognized events of nature, like the sporadic appearance of comets and lightning, the periodic display of stars, planets, and the moon, and biological processes like birth, development, and aging. The rapid progress of science has formulated a firm basis for understanding many of these phenomena, but aging has remained a conspicuous exception. Recently, however, a concerted effort has been made to get at the scientific basis of what cellular and molecular events might cause aging. This perspective will begin with an introduction into new approaches being used to study aging. The main body will focus on two independent studies in a model system that both point to the cell as a probable unit of aging and the nucleolus as a key player in the aging process. Finally, these recent findings will be placed into a context of human aging, which considers a possible interplay between telomeres and the nucleolus, as well as the relationship between dividing and nondividing (postmitotic) cells.

Background

How do we define aging? There are two reliable measures of aging, the first statistical, and the second descriptive (but amenable to quantitation). In the 1820s, a statistician, Gompertz (1825), noted that human mortality rates increase exponentially with age, giving rise to a survival curve depicted in Figure 1A. These kinetics are indicative of a progressive degenerative process and are observed in many organisms, including mammals, flies, worms, plants, and yeast mother cells. These kinetics contrast with stochastic death, for example, by predation, which would give rise to a curve similar to the decay of a radioisotope (Fig. 1B). The second definition of aging is changes in phenotype that occur in all of the individuals over time. In humans it is relatively clear whether someone is young, middle aged, or elderly by their appearance. …