Molecular genetic studies of cellular senescence

  title={Molecular genetic studies of cellular senescence},
  author={O. Pereira-smith and Y. Ning},
  journal={Experimental Gerontology},
The limited doubling potential of normal cells in culture was first proposed as a model for cellular aging by Hayflick in 1961. This phenomenon of in vitro cellular senescence is now well documented for a number of different normal human cell types. In an attempt to determine whether random events or programmed genetic processes were responsible for cellular aging, we performed a series of cell fusion studies. We determined that hybrids from fusion of normal with immortal human cells had… Expand
7 Citations
In vitro study of the mechanisms of senescence acceleration
Culture methods were devised to determine precise population doublings in cultured fibroblast-like cell lines and subsequently compared the aging process, in vitro, in cell lines established from either accelerated senescence-prone or- resistant strains of mice to obtain evidence of accelerated aging. Expand
Induction of erythroid gene expression by microcell fusion.
It is concluded that microcells from erythroid cells contain all the information necessary to induce expression of multiple eryhroid genes and analysis of the components of the microcells responsible for this new gene induction may allow the characterization of cellular factors responsible for erystroid-specific gene expression. Expand
Accelerated aging of dermal fibroblast-like cells from senescence-accelerated mouse (SAM). 1. Acceleration of population aging in vitro
Crisis occurred significantly earlier and the aging process was accelerated in cell lines from SAMP11, compared with lines from SAMR1, and tends to support various observations made in the accelerated senescence-prone strains of SAMP, in vivo. Expand
Emerging technologies: trendy RNA tools for aging research.
Aging is an inevitable biological phenomenon. Attempts to understand its mechanisms and, consequently, to therapeutically decelerate or even reverse the process are limited by its dauntingExpand
Robustness during Aging—Molecular Biological and Physiological Aspects
Here, various properties of robust behavior during human and animal aging are presented, including physiological and molecular biological features, such as the hematocrit, body temperature, immunity against infectious diseases and others. Expand
Unregulated inflammation shortens human functional longevity
  • S. Brod
  • Medicine
  • Inflammation Research
  • 2000
The premature hyperIMmunity of autoimmunity, the local "brain inflammatory response" to Aβ protein in AD, and the immune response to fatty changes in vessels in atherosclerosis all signal the critical importance of unregulated systemic inflammation to common neurological and cardiovascular disease that shortens the nominal longevity of humans. Expand
Ageing is among the greatest known risk factors for most human diseases representing accumulative changes in a human being encompassing physical, psychological and social changes. The drugs andExpand


Hybrids from fusion of normal human T lymphocytes with immortal human cells exhibit limited life span
F fused normal human T lymphocytes with an immortal human cell line to determine whether they could restore the senescent, nondividing phenotype in hybrids, as do normal human fibroblasts, and provides evidence that cellular senescence in T lymphocyte occurs via genetic mechanisms. Expand
Tumor suppression by chromosome 11 is not due to cellular senescence.
The results demonstrate that the introduction of chromosome 11, implicated in tumor suppression, does not cause cellular senescence in three different immortal human cell lines tested. Expand
Immortal phenotype of the HeLa variant D98 is recessive in hybrids formed with normal human fibroblasts
The results indicate that the majority of D98 x HDF hybrid clones exhibit a clear‐cut finite proliferative lifespan phenotype, which leads us to conclude that D98 cells do not express a dominant immortalizing gene. Expand
Reversible cellular senescence: implications for immortalization of normal human diploid fibroblasts.
IMR-90 normal human diploid fibroblasts, transfected with a steroid inducible mouse mammary tumor virus-driven simian virus 40 T antigen, were carried through crisis to yield an immortal cell line.Expand
Evidence for the recessive nature of cellular immortality.
It was found that at least two separate events in the normal cell genome can result in immortality, and in fusions involving certain immortal parent cells, these events can be complemented to result in hybrids with finite division capacity. Expand
  • L. Hayflick
  • Biology, Medicine
  • Experimental cell research
  • 1965
The survival curves obtained with human diploid cell strains are comparable to “multiple-hit” or “ multiple-target” curves obtain with other biological systems where an initial threshold dose is required before an exponential form of the curve is established. Expand
The serial cultivation of human diploid cell strains.
A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level. Expand
Replicative senescence: the human fibroblast comes of age.
Identification of participating genes and clarification of their mechanisms of action will help to elucidate the universal cellular decline of biological aging and an important obverse manifestation, the rare escape of cells from senescence leading to immortalization and oncogenesis. Expand
Expression of SV40 T antigen in finite life-span hybrids of normal and SV40-transformed fibroblasts
Even though viral DNA was present and being expressed in all hybrid clones, the senescent phenotype was dominant in these hybrids, and the change to an indefinite life-span was a rare event. Expand
Functional simian virus 40 T antigen is expressed in hybrid cells having finite proliferative potential.
Fusions with various other immortal cells yielded hybrids that had limited division potential, and T antigen expressed in limited-division hybrids was functional for the induction of cellular DNA synthesis. Expand