Alvaro Macieira Coelho Boeken

Cell biologists have recently become aware that the asymmetry of cell division is an important regulatory phenomenon in the fate of a cell. During development, cell diversity originates through asymmetry; in the adult organism asymmetric divisions regulate the stem cell reservoir and are a source of the drift that contributes to the aging of organisms with renewable cell compartments. Because of the concept of semi-conservative DNA synthesis, it was thought that the distribution of DNA between daughter cells was symmetric. The analysis of the phenomenon in cells during mitosis, however, revealed the asymmetry in the distribution of the genetic material that creates the drift contributing to aging of mammals. On the other hand, cancer cells can originate from a deregulation of asymmetry during mitosis in particular during stem cell expansion. The book describes the phenomenon in different organisms from plants to animals and addresses its implications for the development of the organism, cell differentiation, human aging and the biology of cancers.

In this book, tumour growth is perceived as a deviation from the normal development of the human organism. The molecular, cellular, and tissue determinants of different tumours are discussed showing that each is a different disease, often corresponding to a particular developmental stage. The natural history of several cancers illustrates how clinical incidence can be just the visible part of the iceberg, while the first changes at the tissue level sometimes occur several years before tumour growth becomes manifest. Several mechanisms are proposed to explain the distribution of cancers during the human life span and the decline of the incidence of cancers during human senescence.

The survival of the human species has improved significantly in modern times. During the last century, the mean survival of human populations in developed countries has increased more than during the preceding 5000 years. This improvement in survival was accompanied by an increase in the number of active years. In other words, the increase in mean life span was accompanied by an increase in health span. This is now accentuated by progress in medicine reducing the impact of physiologic events such as menopause and of patho­ logical processes such as atherosclerosis. Up to now,research on aging, whether theoretical or experimental, has not contributed to improvement in human survival. Actually, there is a striking contrast between these significant modifications in survival and the present knowledge of the mechanisms of human aging. Revealed by this state of affairs are the profound disagreements between gerontologists in regard to the way oflooking at the aging process. The definition of aging itself is difficult to begin with because of the variability of how it occurs in different organisms.

This book focusses on an area of increasing interest: the role of the cell matrix in cell regulation

The problem of the long-term proliferation of cells is a seminal one. It has always been a hot subject in biology, a source of far-reaching hypotheses, even more so now when explanations for the mechanisms of cell prolifera tive mortality or immortality seem within our reach. A question which is still debated is whether an infinite division potential can be a normal trait or is always the result of modifications leading to abnormal cell growth and escape from homeostasis. In general, investigators have been advocates of one of the two extremes, universal limited or unlim ited normal proliferative potential. Since the long-term proliferative potential of cells concerns regulation of development, regeneration of tissues, and homeostatic control of cell growth, in brief survival of living organisms, and since the regulation of these processes is so different along the evolutionary scale, it is not surpris ing that there does not seem to be any universal trait. The question of whether cells are endowed with finite or infinite prolifera tive phenotypes has to be seen using the perspective of comparative biology.

The containment of cell growth is essential for the homeostatic regulation of metazoans, and significant advancements have been made in understanding this process. Much of the knowledge stems from identifying molecules with positive and negative regulatory effects on cell proliferation, with a focus on these molecules. Some are already used therapeutically, while others show promise for future applications. This volume illustrates various approaches to this understanding. Control of cell growth is also crucial for comprehending phylogenetic and ontogenetic development. It raises questions about why organisms have evolved complex mechanisms to regulate their size and organ dimensions, how different cells arise—some for renewal and repair, others for specialized functions in a postmitotic state, and germinal cells awaiting signals to initiate new organisms. However, there is a significant gap in knowledge regarding the structural characteristics of cells and how these relate to function. The ability of structure to alter responses to identical signals is not well understood. While positive and negative growth regulators may be conserved, the structural organization of genetic material and other cellular components varies greatly, significantly influencing cell proliferation behavior.