Is cell death and replacement a factor in aging?
ABSTRACT The central theme of the 3rd International Conference on Functional Genomics of Ageing was tissue regeneration as a remedial strategy to address age-related cellular damage and the pathology that ensues. The conference included sessions on maintaining genome integrity and the potential of stem cells to restore function to damaged tissues. In addition to several human syndromes that appear to reflect accelerated ageing, there are now a number of mouse models that prematurely display phenotypes associated with ageing. The intent of this summary presented at the end of the conference was to: (1) discuss various human syndromes and mouse models of accelerated ageing; (2) evaluate whether the phenotypes displayed might result from an elevated rate of cell death coupled with an inability to adequately maintain cell number in various tissues with increasing age; and (3) discuss whether similar events may be occurring during normal ageing, albeit much more slowly.
Article: Carcinogenesis and aging.[show abstract] [hide abstract]
ABSTRACT: Figure 2 illustrates a suggested mechanism of carcinogenesis. This scheme takes into account the effect of carcinogens at different integration levels: subcellular, tissue, and organism. Any of these levels may be age dependent. Age-associated changes in the activity of enzymes responsible for activation and inactivation of carcinogens, and variations in concentrations of lipids and proteins contributing to the transport of carcinogenic agents into cells, may play an important role in the modifying effect of age on carcinogenesis. The effects of age-associated changes in DNA repair need clarification. However, they are thought to exert a permissive influence on the age-associated rise in tumor incidence. It seems that proliferative activity of target tissues is the important modifying factor of carcinogenesis. Age-related changes of regulation at tissue and organism levels are also powerful factors in carcinogenesis modification. Age-dependent changes in the neuroendocrine system provide conditions for metabolic immunodepression and promotion of carcinogenesis. On the other hand, carcinogens per se (especially chemical and radiological) may intensify aging processes in the organism. Normalization, by drugs, of age-associated shifts requiring synthetic and energetic changes of a transformed tumor cells, and of immunological shifts, may exert both antitumor and geroprotective effects.Advances in Cancer Research 02/1983; 40:365-424. · 4.46 Impact Factor
Article: Different types of cell death in organismal aging and longevity: state of the art and possible systems biology approach.[show abstract] [hide abstract]
ABSTRACT: Cell death is as important as cell proliferation for cell turn-over, and susceptibility to cell death is affected by a number of parameters that change with time. A time-dependent derangement of such a crucial process, or even the simple cell loss mediated by cell death impinges upon aging and longevity. In this review we will discuss how cell death phenomena are modulated during aging and what is their possible role in the aging process. We will focus on apoptosis and autophagy, which affect mostly proliferating and post-mitotic cells, respectively, and on mitochondrial degradation in long living cells. Since the "decisional process" that leads the cell to death is very complex, we will also discuss the possibility to address this topic with a systems biology approach.Current pharmaceutical design 02/2008; 14(3):226-36. · 4.41 Impact Factor