Inactivation of p16INK4 tumor suppressor gene function is frequently observed in breast cancer. We examined p16INK4 expression in human mammary epithelial cell (HMEC) cultures established from four normal donors. Normal HMECs divide a limited number of times before proliferation ceases in a state referred to as selection (or M0). The cell subpopulation that emerges spontaneously from selection undergoes a further limited period of proliferation before senescence.
SV40 infection of human cells results in both transformation and lytic infection. We have used origin-defective viral mutants which are unable to replicate in permissive cells to help analysis of transformation. Expression of large T antigen (T ag) and small t antigen results in the altered growth phenotypes characteristic of transformation in other species. Human diploid fibroblasts (HF) have a limited lifespan and undergo senescence; T ag results in extension of lifespan but only in rare cases are the cells capable of continuous growth and are immortal.
The biology of telomeres and telomerase has been the subject of intensive investigative effort since it became evident that they play a significant role in two important biological processes, the loss of cellular replicative capacity inherent to organismal ageing and the unrestricted cell proliferation characteristic of carcinogenesis. Telomere shortening in normal cells is a result of DNA replication events, and reduction beyond a critical length is a signal for cellular senescence.
Odontogenic keratocysts (OKC) present an aggressive course with a marked tendency to recurrence. The epithelium of OKC is thought to have an intrinsic growth potential and has been shown to present a higher rate of proliferation as compared to other types of cyst. bcl-2 has a role in the extension of cell survival. The objective of the present study was to evaluate the bcl-2 protein expression in different odontogenic cysts. A total of 19 dentigerous cysts (DC), 20 radicular cysts (RC) and 14 OKC were used in the present study. DC and RC showed an almost complete negativity for bcl-2.
The proliferative lifespan of normal mammalian cells is limited by intrinsic controls, which desensitize the cell-cycle machinery to extrinsic stimulation after a given number of cell divisions. One underlying clock driving this process of 'replicative senescence' is the progressive erosion of chromosome telomeres, which occurs with each round of DNA replication. This appears to trigger growth inhibition via activation of the tumour suppressor gene (TSG) product, p53, and the consequent up-regulation of the cell-cycle inhibitor p21WAF1.
Mutations in human CuZn superoxide dismutase (SOD) have been associated with familial amyotrophic lateral sclerosis (FALS). Although leading to many experimental advances, this finding has not yet led to a clear understanding of the biochemical mechanism by which mutations in SOD promote the degeneration of motorneurons that causes this incurable paralytic disease.
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
The question of whether aging - the process that converts fit adults into frailer adults with a progressively increased risk of illness, injury, and death - is under genetic control is ambiguous, and its answer depends on what one means by aging. Natural selection can select for genes that retard aging, but only in species and niches where the value of prolonged survival outweighs its costs. Although the form aging takes can be affected by variations at many genetic loci the number of loci that moderate the pace of synchronized decay may be far smaller.
During the course of normal respiration, reactive oxygen species are produced which are particularly detrimental to mitochondrial function. This is shown by recent studies with a mouse that lacks the mitochondrial form of superoxide dismutase (Sod2). Tissues that are heavily dependent on mitochondrial function such as the brain and heart are most severely affected in the Sod2 mutant mouse.
Shortening of telomeres occurs with cell proliferation and correlates well with ageing in humans. Telomerase is a ribonucleoprotein, and is the body's most widely studied mechanism for extension of telomeres to circumvent cellular ageing. Telomerase levels remain at low or unmeasurable levels in most somatic cell populations with only a few exceptions. However, in transformed cell populations, upregulation of telomerase or some other mechanism for telomere extension is required for immortality.
Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics
The potential link between aging and insulin signaling has attracted substantial attention since several decades ago, on the basis of evidence including age-related increase in incidence of insulin resistance, insulin resistance and type 2 diabetes in accelerated aging syndromes and lifespan extension by caloric restriction in rodents. In addition, the intensive investigations in C.