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3.7 - 24th June 1998




Mortality patterns suggest lack of senescence in hydra.

Martinez DE

Department of Biology, Pomona College, Claremont, California 91711-6339, USA.

Exp Gerontol 1998 May;33(3):217-225

Senescence, a deteriorative process that increases the probability of death of an organism with increasing chronological age, has been found in all metazoans where careful studies have been carried out. There has been much controversy, however, about the potential immortality of hydra, a solitary freshwater member of the phylum Cnidaria, one of the earliest diverging metazoan groups. Researchers have suggested that hydra is capable of escaping aging by constantly renewing the tissues of its body. But no data have been published to support this assertion. To test for the presence or absence of aging in hydra, mortality and reproductive rates for three hydra cohorts have been analyzed for a period of four years. The results provide no evidence for aging in hydra: mortality rates have remained extremely low and there are no apparent signs of decline in reproductive rates. Hydra may have indeed escaped senescence and may be potentially immortal.

Sponges (Porifera) model systems to study the shift from immortal to senescent somatic cells: the telomerase activity in somatic cells.

Koziol C, Borojevic R, Steffen R, Muller WE

Institut fur Physiologische Chemie, Universitat, Mainz, Germany.

Mech Ageing Dev 1998 Jan 30;100(2):107-120

Sponges (Porifera) represent the lowest metazoan phylum, characterized by a pronounced plasticity in the determination of cell lineages. In a first approach to elucidate the molecular mechanisms controlling the switch from the cell lineage with a putative indefinite growth capacity to senescent, somatic cells, the activity of the telomerase as an indicator for immortality has been determined. The studies were performed with the marine demosponges Suberites domuncula and Geodia cydonium. It was found that the activity for the telomerase in the tissue of both sponges is high; a quantitative analysis revealed that the extract from S. domuncula contained 10.3 TPG units per 5000 cell equivalents and the one from G. cydonium 8.3 TPG units; hence the activity reached approximately 30-20% of the activity seen in telomerase-positive reference cells. In contrast, dissociated spherulous cells from G. cydonium, after an incubation period of 24 h, contained no detectable telomerase activity. From earlier studies it is known that isolated sponge cells do not proliferate. Based on these findings it is assumed that the separation of the senescent sponge cell lineage from the immortal germ/somatic cell lineage is triggered by the loss of contact with cell adhesion factors. First evidence is included which suggests that the final progress of the senescent, telomerase-negative cells to cell death is caused by apoptosis.

Telomere length dynamics in telomerase-positive immortal human cell populations.

Bryan TM, Englezou A, Dunham MA, Reddel RR

Cancer Research Unit, Children's Medical Research Institute, Westmead, Sydney, NSW, Australia.

Exp Cell Res 1998 Mar 15;239(2):370-378

It has been proposed that the progressive shortening of telomeres in somatic cells eventually results in senescence. Previous experiments have demonstrated that many immortal cell lines have acquired telomerase activity leading to stabilization of telomere length. Telomere dynamics and telomerase activity were examined in the telomerase-positive immortal cell lines HeLa and 293 and subclones derived from them. A mass culture of HeLa cells had a stable mean telomere length over 60 population doublings (PD) in vitro. Subclones of this culture, however, had a range of mean telomere lengths indicating that telomeric heterogeneity exists within a population with a stable mean telomere length. Some of the subclones lacked detectable telomerase activity soon after isolation but regained it by PD 18, suggesting that at least some of the variation in telomere length can be attributed to variations in telomerase activity levels. 293 subclones also varied in telomere length and telomerase activity. Some telomerase-positive 293 subclones contained long telomeres that gradually shortened, demonstrating that factors other than telomerase also act to modulate telomere length. Fluctuations in telomere length in telomerase-positive immortalized cells may contribute to chromosomal instability and clonal evolution.

Independent induction of senescence by p16INK4a and p21CIP1 in spontaneously immortalized human fibroblasts.

Vogt M, Haggblom C, Yeargin J, Christiansen-Weber T, Haas M

Molecular Biology and Virology Laboratory, Salk Institute, San Diego, California 92186-5800, USA.

Cell Growth Differ 1998 Feb;9(2):139-146

In this work, we address the question of whether replicative senescence can be induced in immortal nontumorigenic human fibroblasts. The immortal fibroblasts used in this study were derived from two Li-Fraumeni (LF) patients who carry in their germ line one wild-type and one mutant p53 allele. Both immortal lines have lost the wtp53 allele and express no detectable p16INK4a protein, although they carry the p16INK4a gene. In contrast to immortal human fibroblasts, senescent human fibroblasts have a low content of 5-methyl-cytosine in their DNA. This observation suggested the possibility that a demethylating agent could revert the immortal phenotype and induce replicative senescence in the immortal cell lines. Cells of the two LF lines were exposed to the demethylating agent 5-aza-2'-deoxycytidine. Within 6 days, all cells were growth arrested and showed the enlarged and flat morphology characteristic of senescent cells, an accumulation of lipofuscin granules and senescence-associated beta-galactosidase activity at pH6, both biomarkers for senescence. Immunoblots of 5-aza-2'-deoxycytidine-treated cells showed a greatly increased expression of p16INK4a protein but no detectable change in the expression of p21CIP1, a gene known to be strongly expressed in senescent normal human fibroblasts. In two other experimental series, cells of the two LF lines were infected with retroviral constructs encoding either p16INK4a or p21CIP1. Each of the transduced genes induced senescence without affecting the expression of the other endogenous gene. The results show that induction of senescence in immortal LF fibroblasts can occur by different pathways: (a) by demethylation-dependent pathways that induce the expression of p16INK4a; and (b) by demethylation-independent pathways involving the expression of p21CIP1. The induction of senescence by p16INK4a and p21CIP1 occurred equally in the two human immortal fibroblast lines, which differed in the length of their telomeres and the activity of their telomerase.



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