The Cell Nucleus and Aging: Tantalizing Clues and Hopeful Promises

1855 T here are a handful of biological questions that affect all of us directly in everyday life. How are emotions formed, what is the basis for consciousness, and why do we look the way we do? One that strikes particularly close to home is the question of how we age. The sheer complexity of this problem has had many scientists throw up their hands in frustration and most of the postulated theories have been vague and generally have involved ill-defi ned wear-and-tear mechanisms. But the pursuit of the biological basis of aging has been revitalized within the last decade by studies in yeast, worms, fl ies, and mice that have fi rmly established that there indeed exist specifi c molecular mechanisms that contribute to the aging process [1]. These efforts point to several distinct, likely interrelated, mechanisms, ranging from improper protein metabolism, to alterations of specifi c signaling pathways, progressive damage due to generation of oxidative free radicals, and increased genome instability. Although much has been learned about the aging process from simple model organisms, one intuitively suspects that things might be somewhat different when it comes to human aging. So how does one best study the molecular basis of human aging? The answer might be premature aging diseases, or progeroid syndromes. The advantage of these often rare diseases is that they are mostly monogenic and thus experimentally tractable. On the other hand, one should keep in mind that such disorders usually only mimic some of the features of normal aging and it can be diffi cult to distinguish true aging symptoms from unrelated developmental defects. Regardless, it appears that progeroid syndromes may be legitimately used as model systems to investigate the physiological processes contributing to aging. In fact, the study of some of these diseases has recently brought tantalizing clues as to how we age. One of the most intriguing ones is a possible involvement of structural components of the cell nucleus [2]. The cell nucleus in higher organisms is now recognized as a complex, highly organized repository of an individual's genetic information. The typical nucleus contains distinct functional neighborhoods made up by nonrandomly positioned chromosomes and proteinaceous subcompartments in which specifi c processes, including gene expression, occur [3]. Which molecular mechanisms establish and maintain the structural integrity of the nucleus is largely unknown and represents one of the most exciting fi elds in modern cell biology. Having …