Is cell death and replacement a factor in aging?
University of Minnesota, College of Biological Sciences, St. Paul, MN 55108, United States. Mechanisms of Ageing and Development
(Impact Factor: 3.4).
02/2007; 128(1):13-6. DOI: 10.1016/j.mad.2006.11.004
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.
Available from: Johanna Ojala
- "However, there is no evidence for increased apoptosis during aging, instead it seems that the decline in apoptosis itself leads to the accumulation of damage and functional defects (e.g. Wang, 1997; Zhang and Herman, 2002; Warner, 2007). Replicative senescence in vitro is associated with an increase in resistance to apoptosis (Wang, 1997). "
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ABSTRACT: Innate and adaptive immunity are the major defence mechanisms of higher organisms against inherent and environmental threats. Innate immunity is present already in unicellular organisms but evolution has added novel adaptive immune mechanisms to the defence armament. Interestingly, during aging, adaptive immunity significantly declines, a phenomenon called immunosenescence, whereas innate immunity seems to be activated which induces a characteristic pro-inflammatory profile. This process is called inflamm-aging. The recognition and signaling mechanisms involved in innate immunity have been conserved during evolution. The master regulator of the innate immunity is the NF-kB system, an ancient signaling pathway found in both insects and vertebrates. The NF-kB system is in the nodal point linking together the pathogenic assault signals and cellular danger signals and then organizing the cellular resistance. Recent studies have revealed that SIRT1 (Sir2 homolog) and FoxO (DAF-16), the key regulators of aging in budding yeast and Caenorhabditis elegans models, regulate the efficiency of NF-kB signaling and the level of inflammatory responses. We will review the role of innate immunity signaling in the aging process and examine the function of NF-kB system in the organization of defence mechanisms and in addition, its interactions with the protein products of several gerontogenes. Our conclusion is that NF-kB signaling seems to be the culprit of inflamm-aging, since this signaling system integrates the intracellular regulation of immune responses in both aging and age-related diseases.
Available from: Vladimir N Anisimov
- "The homeostatic regulation of cell numbers in normal tissues reflect a precise balance between cell proliferation and cell death. Programmed cell death (apoptosis) provides a protective mechanism of protection from cancer, by removing senescent, DNA damaged, or diseased cells that could potentially interfere with normal function or lead to neoplastic transformation (Hanahan and Weinberg, 2000; Warner, 2007). Apoptosis plays a substantial role in many other aspects of aging and cancer, including control of the life span of most members of the immune complex, and the rate of growth of tumors (Zhang and Herman, 2002). "
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ABSTRACT: Carcinogenesis is a multistage process: neoplastic transformation implies the engagement of a cell through sequential stages, and different agents may affect the transition between continuous stages. Multistage carcinogenesis is accompanied by disturbances in tissue homeostasis and perturbations in nervous, hormonal, and metabolic factors which may affect antitumor resistance. The development of these changes depends on the susceptibility of various systems to a carcinogen and on the dose of the carcinogen. Changes in the microenvironment may condition key carcinogenic events and determine the duration of each carcinogenic stage, and sometimes they may even reverse the process of carcinogenesis. These microenvironmental changes influence the proliferation rate of transformed cells, the total duration of carcinogenesis and, consequently, the latent period of tumor development. Aging may increase or decrease the susceptibility of various tissues to initiation of carcinogenesis and usually facilitates promotion and progression of carcinogenesis. Aging may predispose to cancer by two mechanisms: tissue accumulation of cells in late stages of carcinogenesis and alterations in internal homeostasis, in particular, alterations in immune and endocrine system. Aging is associated with number of events at molecular, cellular and physiological levels that influence carcinogenesis and subsequent cancer growth.
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ABSTRACT: In humans, aging is inexorable. The progressive decrease in physiological capacity and the reduced ability to respond to enviro n- mental stresses lead to increased susceptibility and vulnerability to disease. Consequently, mortality due to all causes increa ses exponentially with aging. Attempts at understanding the causes of aging are limited by the complexity of the problem. Aging changes are manifest from the molecular to the organismic level; environmental factors affect experimental observations; sec- ondary effects complicate elucidation of primary mechanisms; and precisely defined, easily measurable "biomarkers" are lacking. No one unifying theory may exist, since the mechanisms of aging could be quite distinct in different organisms, tissues, and ce lls. Evolutionary pressures have selected for successful reproduction, making it likely that the post-reproductive physiology of an organism (i.e., aging) is an epigenetic and pleiotropic manifestation of the optimization for early fitness. Indeed, antagonist ic pleiotropy, wherein genes that enhance early survival and function but are disadvantageous later in life, may play an overridin g role in aging. Theories of aging can be divided into two general categories: stochastic and developmental-genetic. These are no t mutually exclusive, particularly when considering the free radical/mitochondrial DNA theory of aging. Increasing evidence sug- gests that cellular senescence and organismic aging are antagonistically pleiotropic manifestations of evolutionary pressures t o pre- vent malignant transformation. In other words, aging may be the price we pay to avoid cancer. The beneficial paradox may be tha t the maximum lifespan potential of humans may have been achieved, in part, due to our ability to grow old.
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