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: 3.26). 02/2007; 128(1):13-6. DOI: 10.1016/j.mad.2006.11.004
Source: PubMed

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.

  • The Journals of Gerontology Series A Biological Sciences and Medical Sciences 06/2010; 65(6):580-9. · 4.31 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Alumni bulletin - School of Dentistry, Indiana University 02/1978;
  • Source
    [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 12/2007; 14(3):226-236. · 3.31 Impact Factor