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Importance of mitochondrial uncoupling and telomere dynamics in the free radical theory of ageing

Gesuchsteller/in Bize Pierre
Nummer 124988
Förderungsinstrument Projektförderung (Abt. I-III)
Forschungseinrichtung Département d'Ecologie et d'Evolution Faculté de Biologie et de Médecine Université de Lausanne
Hochschule Universität Lausanne - LA
Hauptdisziplin Oekologie
Beginn/Ende 01.11.2009 - 31.10.2012
Bewilligter Betrag 375'000.00
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Alle Disziplinen (3)

Disziplin
Oekologie
Zoologie
Molekularbiologie

Keywords (13)

ageing; free radical; oxidative stress; uncoupling; brown adipose tissue; telomere; bird; life expectancy; life history theory; lifespan; nonshivering thermogenesis; telomeres; vertebrates

Lay Summary (Englisch)

Lead
Lay summary
Because ageing is a 'detrimental phenomenon', how ageing evolves and persists in natural populations and what are the proximate mechanisms remain poorly understood and controversial. Several ageing theories have been proposed, and one of the most influential is that animals age because molecules, cells, tissues, organs and ultimately animals accumulate oxidative damage over time (i.e. the free radical theory of ageing). Oxidative damage occurs when the production of free radicals exceeds the antioxidant defences and the repair mechanisms. Hence, it is thought that ageing is modulated by variation in the production of free radicals and by variation in the rate of accumulation of oxidative damage. Free radicals are mostly produced during respiration in the mitochondria, and the uncoupling to survive hypothesis recently proposed that the production of free radicals is reduced when energy available in the electrochemical proton gradient for the synthesis of ATP is dissipated as heat by uncoupling proteins (UCPs, and especially UCP1). Brown adipose tissue is rich in mitochondria and UCP1, the latter being essential for heat production via adaptive nonshivering thermogenesis. Body temperature maintenance accounts for a large part of the energy budget of wild animals, and thus thermal selection on uncoupling and nonshivering thermogenesis may explain part of the variation in animal life histories across latitudinal and altitudinal gradients. Using wild-derived common voles as study system, we are investigating whether selection on nonshivering thermogenesis mediates the life history trade-off between reproduction and survival.Telomeres are specialized nucleotide repeat sequences at the ends of eukaryotic chromosomes that shorten at each cell division because of the incapacity of the normal DNA replication process to fully copy the chromosome end. Evidence is accumulation from in vitro studies that telomere erosion is accelerated by oxidative stress, and that once a critical telomere length is reached, cells stop dividing and enter a state of replicative senescence, which may be followed by apoptosis. Hence, it has been suggested that telomere length plays a crucial role in tissue functioning, and by extension, in the life expectancy of whole organisms. Using free-living Alpine swifts as study system, we take benefit of a large existing database in order to investigate the consequences of early growth conditions and adult lifestyle on telomere dynamics and thereby life expectancy.Together, these projects should shed new light on the role of uncoupling and telomere dynamics in the basis biology of ageing, with the aim to reveal poorly understood connections of biological and medical importance between metabolism, free radical production, telomere dynamics and life expectancy.
Direktlink auf Lay Summary Letzte Aktualisierung: 21.02.2013

Verantw. Gesuchsteller/in und weitere Gesuchstellende

Mitarbeitende

Publikationen

Publikation
Effects of brood size manipulation and common origin on phenotype and telomere length in nestling collared flycatchers
Voillemot M. Hine K. Zahn S. Criscuolo F. Gustaffson L. Doligez B. Bize P. (2012), Effects of brood size manipulation and common origin on phenotype and telomere length in nestling collared flycatchers, in BMC Ecology , 12, 17.
Selection on age at first and at last reproduction in the long-lived Alpine swift Apus melba
Tettamanti F. Witvliet W. Bize P. (2012), Selection on age at first and at last reproduction in the long-lived Alpine swift Apus melba, in Ibis, 154, 338.
Experimental evidence that adult antipredator behaviour is heritable and not influenced by behavioural copying in a wild bird
Bize P. Diaz C. Lindström J. (2011), Experimental evidence that adult antipredator behaviour is heritable and not influenced by behavioural copying in a wild bird, in Proceedings of the Royal Society of London B, 279, 1380.
Female-biased infection and transmission of the gastrointestinal nematode Trichuris arvicolae infecting the common vole
Sanchez A. Devevey G. Bize P. (2011), Female-biased infection and transmission of the gastrointestinal nematode Trichuris arvicolae infecting the common vole, in International Journal For Parasitology, 41, 1397.
Constraint and cost of oxidative stress on reproduction: correlative evidence in laboratory mice and review of the literature
Stier A. Reichert S. Massemin S. Bize P. Criscuolo F., Constraint and cost of oxidative stress on reproduction: correlative evidence in laboratory mice and review of the literature, in Frontiers in Zoology, in press.

Zusammenarbeit

Gruppe / Person Land
Formen der Zusammenarbeit
CNRS Lyon Frankreich (Europa)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Forschungsinfrastrukturen
CNRS Strasbourg Frankreich (Europa)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Austausch von Mitarbeitern
UNI Berne Schweiz (Europa)
- vertiefter/weiterführender Austausch von Ansätzen, Methoden oder Resultaten
- Publikation
- Forschungsinfrastrukturen

Wissenschaftliche Veranstaltungen

Aktiver Beitrag

Titel Art des Beitrags Titel des Artikels oder Beitrages Datum Ort Beteiligte Personen
MeetOchondrie 26.09.2012 Soustons, France
Experimental Biology 29.06.2012 Salzburg, Austria
8th Meeting Ecology & Behaviour 02.05.2012 Chizé, France
Ageing & Longevity Meeting 10.11.2011 Changins, Switzerland
Biology11 03.02.2011 Zurich


Verbundene Projekte

Nummer Titel Start Förderungsinstrument
109009 Life history consequences of early developmental conditions 01.09.2005 Stipendien für fortgeschrittene Forschende
144203 Linking endothermy and mitochondrial proton leak to life history variation 01.11.2012 Projektförderung (Abt. I-III)

Abstract

Because ageing is a ‘detrimental phenomenon’, how ageing evolves and persists in natural populations and what are the proximate mechanisms remain poorly understood and controversial. Several ageing theories have been proposed, and one of the most influential is that animals age because molecules, cells, tissues, organs and ultimately animals accumulate oxidative damage over time (i.e. the free radical theory of ageing). Oxidative damage occurs when the production of free radicals exceeds the antioxidant defences and the repair mechanisms. Hence, it is thought that ageing is modulated by variation in the production of free radicals and by variation in the rate of accumulation of oxidative damage. It has been suggested that variation in the production of free radicals is important in shaping ageing in short-lived species, and variation in the maintenance/repair mechanisms that govern the accumulation of oxidative damage in long-lived species. Hence, in this project divided in two PhD proposals with two different study systems, we will investigate (A) how mitochondrial uncoupling, and in turn free radical production, shapes the life histories in a short-lived rodent, the common vole (Microtus arvalis); and (B) whether telomere dynamics, a proxy of oxidative damage, produce the link between early growth condition, lifestyle and ageing in a long-lived bird, the Alpine swift (Apus melba).Free radicals are mostly produced during respiration in the mitochondria, and the uncoupling to survive hypothesis recently proposed that the production of free radicals is reduced when energy available in the electrochemical proton gradient for the synthesis of ATP is dissipated as heat by uncoupling proteins (UCPs, and especially UCP1). Brown adipose tissue is rich in mitochondria and UCP1, the latter being essential for heat production via adaptive nonshivering thermogenesis. Body temperature maintenance accounts for a large part of the energy budget of wild animals, and thus thermal selection on uncoupling and nonshivering thermogenesis may explain part of the variation in animal life histories across latitudinal and altitudinal gradients. Using wild-derived common voles from high and low land populations as study system, we will perform series of laboratory and field experiments in order (A1) to investigate covariations along an altitudinal gradient in brown adipose tissue regulation, susceptibility to oxidative stress, reproductive success and lifespan; and (A2) to test if brown adipose tissue and mitochondrial uncoupling mediate the life history trade-off between reproduction and survival.Telomeres are specialized nucleotide repeat sequences at the ends of eukaryotic chromosomes that shorten at each cell division because of the incapacity of the normal DNA replication process to fully copy the chromosome end. Evidence is accumulation from in vitro studies that telomere erosion is accelerated by oxidative stress, and that once a critical telomere length is reached, cells stop dividing and enter a state of replicative senescence, which may be followed by apoptosis. Hence, it has been suggested that telomere length plays a crucial role in tissue functioning, and by extension, in the life expectancy of whole organisms. Using free-living Alpine swifts as study system, we will take benefit of a large existing database in order (B1) to test the consequences of early growth conditions and adult lifestyle on telomere dynamics and thereby life expectancy; and (B2) to investigate covariations between age, oxidative stress, telomerase activity and telomere dynamics.The objectives of this project are original because very little is known on ageing in the wild, and tests of the free radical theory of ageing in natural populations are crucial to pinpoint general biological mechanisms. Together, these experiments should shed new light on the role of uncoupling and telomere dynamics in the basis biology of ageing, with the aim to reveal poorly understood connections of biological and medical importance between metabolism, free radical production, telomere dynamics and life expectancy.
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