Alvaro Macieira-Coelho – författare

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.

This volume gives the reader a comprehensive overview of the fundamental and biological aspects of aging. First, the field is described from a historical perspective. Then, the author analyzes the three fundamental mechanisms of survival: energy utilization, molecular and cellular redundancy, and the organization of information. The genetics of aging is reviewed rejecting some simple-minded interpretations. A bridge is established between the molecular, cellular, and tissue modifications that have been reported in the literature, and the clinical manifestations of the aging syndrome. Special relevance is given to the problem of the supposed association between cancers and aging, giving a new interpretation of that relationship.

This book describes the most outstanding theoretical hypotheses aiming at explaining the infinite proliferative potential of a cell population, what is now known under the term cell immortalization. It elucidates the phenomenon from an evolutionary point of view, and describes the cell systems used and the experiments performed at the cellular and molecular levels to determine the mechanisms responsible for this cell property. It also appraises how the mortal and immortal phenotypes reflect characteristics of the respective organism, and stresses how this goes beyond the proposal that its opposite, the mortal phenotype, is a mechanism to protect the organism against cancer.

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.

This book describes the most outstanding theoretical hypotheses aiming at explaining the infinite proliferative potential of a cell population, what is now known under the term cell immortalization. It elucidates the phenomenon from an evolutionary point of view, and describes the cell systems used and the experiments performed at the cellular and molecular levels to determine the mechanisms responsible for this cell property. It also appraises how the mortal and immortal phenotypes reflect characteristics of the respective organism, and stresses how this goes beyond the proposal that its opposite, the mortal phenotype, is a mechanism to protect the organism against cancer.

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.

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.

The genetic information contained in a cell needs the appropriate environment to express itself, not only the intracellular environment but also the extracel- lular one. The latter is provided to a great extent by the molecules which constitute the extracellular matrix. On the one hand, the matrix creates inter alia the right pH and osmotic envi- ronment and allows the diffusion of messengers targeting the cell membrane; on the other hand, it has a mechanical effect whose relevance began to be understood 28 years ago. Basically, the messages that reach the cell and are then transported to the genome depend on molecular conformational flexibility. Molecular structures usually prevail because they represent states of minimum potential energy cre- ating energy barriers which are activated through conformational changes. From the periphery to the nucleus the information flows through the activa- tion of energy barriers. The tools used to switch from low-energy to high- energy molecular configurations are: the binding of ligands to their receptors, gradients of electrochemical potential created by ion pumps, Ca2+ mobiliza- tion, and phosphorylation and dephosphorylation.Variation in molecular con- figuration through molecular binding is in itself sufficient to trigger ion pumps and activate kinases and phosphatases. This is one aspect of the mechanical role of the extracellular matrix dealt with herein: the induction of molecular and supramolecular conformational modifications through interactions with the cell membrane, which promote the transduction and centripetal progression of signals.