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Results for “replicative lifespan”

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PubMed1983

Influence of age and diet on DNA synthesis and the DNA content of mid-gut cells in the dipteran Sarcophaga carnaria.

Virgin female Sarcophaga carnaria maintained on a diet of sugar and water had shorter lifespans than those maintained on a liver, sugar and water diet; there was no significant different between the lifespans of mated females or mated males kept on the two diets. Autoradiographs of mid-gut sections from virgin females which had been fed with [3H]thymidine showed substantial amounts of DNA synthesis in the nuclei during at least the first 14-15 days of adult life. Cytophotometric measurements of Feulgen-stained mid-gut nuclei of 0--1-, 2--3-, and 14--15-day-old females showed that the integrated absorbances peaked at values corresponding approximately to 2 C, 4 C, 8 C, 16 C and 32 C. The proportion of nuclei with the higher Feulgen-DNA values increased with age, and was greater in flies maintained on the liver, sugar and water diet. It is suggested that the DNA synthesis observed is associated with polytenization rather than mitotic cell division, and that the level of polyteny reached may reflect age- and diet-related differences in the functional demand made on mid-gut cells.

Aging↗

PubMed2003

Alterations in stress cortisol reactivity in depressed preschoolers relative to psychiatric and no-disorder comparison groups.

BACKGROUND: Despite the robust and widely replicated finding of elevated hypothalamic-pituitary-adrenal (HPA) axis reactivity in depressed adults, studies of depressed children have yielded ambiguous findings. Animal models of early depression and studies of children experiencing early psychosocial deprivation have suggested that alterations in HPA axis reactivity are evident in early "depressive-like" conditions. The current study is, to our knowledge, the first investigation of HPA axis reactivity in very young children with a clinical depressive syndrome for which content validity has been established. METHODS: Depressed, psychiatric, and no-disorder comparison children aged 3 through 5.6 years were studied for HPA axis reactivity in response to experimental psychosocial stressors. The children were diagnosed using a developmentally appropriate, structured psychiatric interview. Salivary cortisol was obtained at 3 time points during a laboratory assessment before and after stressors involving separation from the parent and frustrating tasks. RESULTS: Repeated measures of multivariate analysis of variance revealed a significant interaction between the diagnostic group and 2 cortisol percent change scores. Depressed preschoolers displayed a pattern of increasing cortisol levels throughout the assessment in response to both separation and frustration stressors. In contrast, both comparison groups showed decreasing cortisol levels in response to the separation stressor. All groups displayed increasing cortisol levels in response to frustrating tasks. Preschoolers with a presumptive melancholic depressive subtype displayed these alterations at a greater magnitude relative to comparison groups. CONCLUSIONS: To our knowledge, these findings are the first to demonstrate altered HPA axis reactivity in depressed preschoolers. These alterations are consistent with those described in depressed adults and in animal models of early depression. These findings provide evidence for possible continuity of HPA axis alterations in depressive disorders across the lifespan and are discussed in the context of prior studies of HPA axis reactivity in clinically depressed children and adolescents, suggesting that younger age and inpatient status are features associated with altered HPA axis reactivity.

Arousal↗

PubMed1992

Elongation factor-1 alpha gene determines susceptibility to transformation.

Elongation factor-1 alpha (EF-1 alpha), an essential component of the eukaryotic translational apparatus, is a GTP-binding protein that catalyses the binding of aminoacyl-transfer RNAs to the ribosome. Expression of the EF-1 alpha gene decreases towards the end of the lifespans of mouse and human fibroblasts, but forced expression of EF-1 alpha prolongs the lifespan of Drosophila melanogaster. Eukaryotic initiation factor-4E, another component of the translational machinery, is mitogenic or oncogenic when constitutively expressed in some mammalian cells. Thus, components of the protein synthesis apparatus seem to be involved in the control of cell proliferation. Using expression cloning, we have isolated a complementary DNA clone from a BALB/c 3T3 mouse fibroblast variant, A31-I-13 (ref. 10), which specifies a factor determining the susceptibility of BALB/c3T3 to chemically and physically induced transformation. Here we report that the factor is EF-1 alpha and that its constitutive expression causes BALB/c 3T3 A31-I-1 (ref. 10), C3H10T1/2 (ref. 11) and Syrian hamster SHOK fibroblasts to become highly susceptible to transformation induced by 3-methylcholanthrene and ultraviolet light. EF-1 alpha messenger RNA is also constitutively expressed in a quiescent culture of the highly susceptible variant A31-I-13. We conclude that the removal of regulation of the expression of these components of the translational machinery may predispose cells to become more susceptible to malignant transformation.

3T3 Cells↗

PubMed1985

In vivo DNA synthesis in the dietary restricted long-lived rat.

Male CFY Sprague-Dawley rats maintained at 50% growth rate of ad libitum fed, age-matched control animals showed a 42% extension in maximum lifespan and an increase in the overall doubling time of the rate of mortality from 102 days to 203 days. The slower growth rate of animals on the restricted diet was reflected in lower DNA, RNA, and protein content of liver, kidney and heart with age. DNA synthesis in vivo measured by the incorporation of 3H-thymidine was severely inhibited in liver, kidney, heart, and abdominal skin, particularly during the first six months of life. The developmental peak in DNA synthesis observed in liver and kidney of ad libitum fed animals before 100 days of age was completely inhibited. No effect of restricted feeding on DNA synthesis in the small intestine was observed; however, DNA synthesis was higher in thymic tissue from the experimental animals. A decrease in RNA content of liver, kidney, and heart preceded any change in protein or DNA in animals subjected to restricted feeding. The capacity for protein synthesis (RNA/DNA ratio) was decreased by restricted feeding and was associated with a reduced protein/DNA ratio indicative of reduced cell size during the first six months of life. The translational activity per ribosome (protein/RNA ratio) was not disturbed by undernutrition in any of the tissues studied.

Animal Nutritional Physiological Phenomena↗

PubMed1987

[Possibilities and limitations of fibroblast cultures in the study of animal aging].

INTRODUCTION. Aging--the effect of time--occurs in every living organism. Senescence is the last period of the lifespan, leading to death. It happens in all animals, with the exception of a few didermic species (Hydras) having a stock of embryonic cells and being immortal. The causes of animal senescence are badly known. They depend both on genetic characters (maximal lifespan of a species) and on medium factors (mean expectation of life of the animals of a species). Animal senescence could depend on cell aging: 1) by senescence and death of the differentiated cells, 2) by modified proliferation and differentiation of the stem cells of differentiated tissues, 3) by alterations in the extracellular matrices, 4) by interactions between factors 1) 2) and 3) in each tissue, 5) by interactions between the several tissues of an organism. This complexity badly impedes the experimental study of animal senescence. Normal mammal cells are aging when they are cultivated (in vitro ageing): their phenotype varies and depends on the cell generation (in vitro differentiation); the last cell-generation doesn't divide anymore and declines until death of the culture (in vitro senescence). Analysis of these artificial but well controlled systems allows an experimental approach of the proliferation, differentiation, senescence and death of the cells and of the extracellular matrix functions. Present literature upon in vitro aging of cultivated human cells is essentially made of papers where proliferation and differentiation characteristics are compared between early ("young") and late ("old") cell-generations of the cultures. FIBROBLASTIC CELLS OF THE MOUSE SKIN. This cell type has been studied in our laboratory, using different systems: 1) Primary cultures isolated from peeled skins of 19 day old mouse embryos, 2) Mouse dermis analyzed in the animals, 3) Cultivated explants of skins, 4) Serial sub-cultures of fibroblasts isolated from these explants, 5) Cells cultivated comparably on plane substrates (glass, plastic, collagen films) and on tridimensional matrices (collagen fibres). Systems 2), 3), 4) and 5) have been obtained either from 19 day old embryos or from 6 groups of animals of different ages (from 1/2 till 25 month). In primary cultures (system 1) all the cell generations have been analyzed, including the last one until death of the culture. We have shown that many characters are varying with cell-generation: cell form and cell mass, rate of DNA replication and cell division, rate of RNA transcription, nature of the accumulated and of the synthetized proteins, organization of the cytoskeletal elements, organization of the extracellular matrix, type of cell death.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1993

Establishment and characterization of first trimester human trophoblast cells with extended lifespan.

We established trophoblast cell cultures with extended lifespans by introducing into first trimester human trophoblasts the gene encoding simian virus 40 large T antigen. The transfected trophoblasts were characterized according to their expression of various morphological and functional markers. Both parental (HTR-8) and transfected (HTR-8/SVneo) lines were morphologically similar and positive for cytokeratin, confirming their epithelial (trophoblastic) identity. Whereas the parental cells senesced after 12-14 passages, the transfectants have been in culture for over 32 passages. Human chorionic gonadotrophin was detected only in the HTR-8/SVneo cells and not in the parental cells. Both lines required at least 5% serum in order to sustain growth in vitro and responded to transforming growth factor-beta (TGF-beta) with reduced [3H]-thymidine incorporation in a dose-dependent manner. Treatment with TGF-beta also resulted in decreased secretion of plasminogen activators (PAs) and reduced PA activity by both lines. Both cell lines secreted mostly 72-kDa type IV collagenase as determined by substrate gel zymography, but the level of secretion of this enzyme was not significantly affected by TGF-beta in either line. Even though both lines exhibited similar in vitro invasive abilities, only the invasiveness of the parental cells was reduced by TGF-beta. Neither parental or transfected cells were capable of growth in soft agar and no sign of tumor formation was evident more than 5 months after subcutaneous inoculation of the transfected cells into nude mice. These results indicate that apart from their ability to sustain prolonged growth in culture, the transfected HTR-8/SVneo cells share a number of phenotypic properties with the parental trophoblast cells. For this reason, these transfected trophoblasts may prove to be an important tool for the study of placental function and/or tumor progression.

Animals↗