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J Tréton

Publications and source records attributed to J Tréton.

6 recordsLinked to original sources

[Fundamental aspects of extreme aging].

Major developments in molecular biology in invertebrates have recently shown the determining effect of genetics on aging. The first finding was that artificial selection can highlight the genetic aspect of the aging process, demonstrating the polygenetic property of longevity. Another finding showed that certain gene transfers can modulate the lifespan of an organism. Recent progress has been made in three fields: genetic markers of aging, biological basis of cell maintenance, and hereditary factors contributing to late onset genetic disease. These new developments open new avenues of research in clinical biology. In regard to genetic markers of aging, it has been demonstrated that the ends of the chromosomes, telomeres, play a role in cell senescence. Telomeres can be viewed as markers of aging. Shortened telomeres are associated with replicative senescence and antitumor action. DNA anomalies are also more frequent: simple or double breaks, additions and base substitutions. Data on the biological basis of cell maintenance obtained in invertebrates show the polygenetic property of aging involving four significant mechanisms, control of metabolism, resistance to stress, chromatin-dependent gene regulation of genetic homeostasis. Finally, recent studies have shown that late onset hereditary diseases would be linked with particular genes, some of which have been identified. Two non-exclusive mechanisms could be involved: an adaptive mechanism involving gene selection during the evolutionary process, for example in obesity; and non-adaptive accumulation of gene expression during the post-reproductive phase, for example in Alzheimer's disease. These findings open a new era for the biology of aging.

Aged↗

A caspase-independent cell clearance program. The LEI/L-DNase II pathway.

The discovery of caspase-mitochondrial pathway counts as one of the most important discovery in apoptosis biochemistry. Today, however, we begin to recognize its limits. Inhibition of caspase does not prevent cell death in many mammalian models. Targeted disruption of caspases does not impair every type of apoptosis. Other pathways, caspase independent, are now described. Here we present one of these pathways. It is a serine-protease dependent pathway and its key event is the transformation of LEI (a serine protease inhibitor) into L-DNase II (an endonuclease). When using this apoptotic pathway the cell activates, at the same time, its endonuclease activity (L-DNase II appears) and its protease activity (there is a release of inhibition of proteases).

Animals↗

Multiple deletions in mitochondrial DNA are present in senescent mouse brain.

We report for the first time that multiple deletions occur during ageing of mice brain mitochondrial DNA (mtDNA). Deletions were detected by electrophoresis after amplification using the nested Polymerase Chain Reaction (N-PCR) method. Three mutant mtDNAs with 3726-, 3867- and 4236-bp deletions were directly detected by N-PCR which were undetectable in young brain mice. Each deletion was sequenced: in the region containing the junction fragment three different repeats of 13, 14 and 15 bp were observed. These results support the hypothesis that direct repeats are an initiating factor involved in ageing-associated accumulation of deletion.

Aging↗

A senescence up-regulated protein: the rat thyroxine-binding globulin (TBG).

Thyroxine-binding globulin (TBG), the major carrier of thyroid hormones in human serum, was thought to be absent in most species, including rodents. We demonstrated recently that in fact the rat possesses a TBG gene, virtually non-expressed in young adults, but actively transcribed during post-natal development. We now find that the TBG gene is also increasingly re-expressed during senescence. Evidence is presented suggesting that physiologically decreased thyroid hormone levels, characteristic of neonates and of ageing rats, might constitute a common factor inducing up-regulation of TBG in both developmental and ageing processes. Rat TBG is to our knowledge the first biochemical 'positive' (i.e. increasing) marker of non-pathological senescence, expressed at both biosynthetic and bloodstream levels.

Aging↗

Evidence for a relationship between longevity of mammalian species and a lens growth parameter.

The lens growth was studied in a number of curves representing 16 mammalian species. Emphasis was placed on determining the length of the lens development stage. All the lens curves studied went through a growth crisis: It is a period of apparent growth slowing down, lasting linear during the resting lifespan (adult stage). The growth crisis occurred at a length that was characteristic for the species and was shown to be directly correlated with the species maximum lifespan potential. These results may indicate the prevalence of a common functional basis regulating the lens growth and thus operating in the longevity of mammalian species.

Animals↗