![]() ![]() The two main causes of death (cardiovascular diseases and cancer) are, for example, respectively attributed to failure in preventing damage to and preserving the coating of blood vessels, and to signal transduction mechanisms that regulate cell division. Relation between cell or tissue dysfunction and certain age-related diseases. mentions in Table 1 a number of structures or processes which go beyond the capacity of cells and tissues to maintain balance, resulting in certain pathologies that emerge in old age. Cambridge: Cambridge University Press, 1995. Nature Reviews Molecular Cell Biology, v. Towards an e-biology of aging: integrating theory and data. Methodological innovations based on computer modeling of interactions and synergism between different aging mechanisms have contributed to building a better and more integrated view of how cells degrade with age ( KIKWOOD et al., 2003 KIRKWOOD, T. ![]() ![]() The obvious response to this shortcoming is to admit that cellular aging is multifactorial and that several mechanisms act synergistically towards the final result. However, their individual contribution to senescence seems invariably too small for their mechanism alone to account for biological age-related degeneration. For each one of them there is evidence to support the hypothesis that it is actually a senescence agent. Several different mechanisms may contribute to cell aging and disease. In addition to these interferences, it has become apparent that, with age, progressive changes of an epigenetic nature occur in the genome, especially changes in DNA methylation, which may have profound effects on gene expression and cell function. Particularly significant are the contributions to cellular DNA damage induced by ROS through: 1) damage to chromosomal DNA in the cell nucleus, resulting in alteration of the normal function of genes or mutations 2) damage to telomeres, protective structures of DNA that appear as a cover at the end of chromosomes 3) DNA damage within organelles of energy-generating cells (mitochondria), disrupting the production of energy. Stress, DNA damage and ageing: an integrative approach. VON ZGLINICKI et al., 2001 VON ZGLINICKI, T. Genetic analysis of ageing: role of oxidative damage and environmental stresses. Recent evidence suggests that a major link between many different types of cell and tissue damage is the action of reactive oxygen species (ROS), which are generated as byproducts of the essential use of oxygen by the body to produce cell energy ( MARTIN et al., 1996 MARTIN, G. SNP1 and SNP2: polymorphism involving single nucleotides. : conceptual model of the main factors that influence cell function during the course of life, with modifications that modulate the aging trajectory. Pulses and carcinogenesis: potential for prevention of colon, breast and other cancers. The health pendulum: adapted from Mathers (2002) MATHERS, J. What is clear, however, is that in terms of the fundamentals that drive aging, there is continuity between events happening in early age and those manifested in old age, as suggested by the pendulum model presented by Mathers (2002) MATHERS, J. Whether these effects are indeed mediated by adaptive plasticity, affecting the allocation of metabolic resources for somatic maintenance remains to be discovered and understood. Living with the past: evolution, development, and patterns of disease. International Journal of Epidemiology, v. Fetal origins of adult diseases: strength of effects and biological basis. The hypothesis of adaptive plasticity related to aging and longevity is still valid, i.e., an adaptive capacity to change the course of life history in response to adverse circumstances, as has been confirmed by the discovery that the fetal nutritional environment can change the risk of disease development in adults ( BARKER et al., 2002 BARKER, D. as: cumulative, progressive, intrinsic, and deleterious, represented by the acronym CUPID. Such changes were classified and adopted by Arking (2008) ARKING, R. ![]() Over the years, the increasing levels of these defects interfere with the performance and amount of functional tissues in different organs, resulting in weakness, functional disability and disease ( KIRKWOOD, 2005 KIRKWOOD, T. The process of chronological and biological aging results in a buildup of molecular damage that occurs throughout life, resulting in a gradual increase in the number of defective cells and metabolic changes. ![]()
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