RESEARCH
Longevity and ageing have been the focus of many humans, from philosophers to biologists. We all age and die, but there is considerable heterogeneity in ageing rate and lifespan, both within and between species. For instance, just think about Jeanne Calment, the famous French who lived to the age of 122 years, or to the difference in maximum lifespan between house mouse (4 years) and Asian elephant (65 years). While ageing is undoubtedly a complex and multifactorial process, it has been suggested that mitochondrial dysfunction, oxidative stress and telomere shortening are key hallmarks of the ageing process. Mitochondria are the powerhouse of eukaryotic cells, they convert nutrients into a form of energy usable by the cell (ATP), but at the same time are inevitably by-producing potentially deleterious molecules such as reactive oxygen species (ROS). ROS are highly reactive molecules that can damage our cellular components (i.e. oxidative damage on DNA, protein, lipids) if they are not detoxified by antioxidant defences; a situation known as oxidative stress. Oxidative stress contributes to accelerate telomere shortening, telomeres being non-coding DNA structures protecting the extremities of our chromosomes. Critically short telomeres induce senescence at the cellular level, and telomere length has been shown to predict survival/lifespan in human and several other taxa, with some of the best examples being in captive and wild bird species.
My research aims at better understanding the role of mitochondrial function, oxidative stress and telomere shortening in the ageing process, and at identifying the environmental factors leading to inter-individual differences in such hallmarks of the ageing process.
Mitochondrial function, ageing & life histories
Mitochondrial function determines both ATP and ROS production, but it seems that decreasing mitochondrial efficiency to produce ATP could reduce ROS production and increase longevity (uncoupling to survive hypothesis). Yet, this is likely to lead to a reduction in energy investment toward important functions such as growth or reproduction. To test these ideas, I conduct experiments in the lab using DNP, a chemical know to decrease mitochondrial efficiency and used illegally as a diet pill by humans. In addition, I also study relationships between mitochondrial efficiency and life history traits in wild populations to better understand the causes and consequences of the natural differences exisiting among individuals in mitochondrial function.
Early-life determinants of the hallmarks of ageing
We know that the conditions we experienced during early-life are important for our health later in life, as best exemplified by the impact of low birth weight in human on the risks later in life to develop diabetes and cardiovascular diseases. I am interested in the consequences that early-life conditions have on mitochondrial function, oxidative stress and telomere length, since alterations of such hallmarks of ageing could explain the long-term consequences of poor early-life conditions. To do so, I am investigating the impact of poor pre- and postnatal conditions using both experiments in the lab (e.g. manipulations of development using temperature or resource availability) and in the wild (e.g. manipulations of hormonal exposure). I also use natural variations in early-life conditions linked to particular environmental constraints (e.g. timing of breeding, altitude, intra-brood competition) to determine the importance of early-life conditions under more natural conditions.
Environmental stress and the hallmarks of ageing
While early-life conditions seem important, the environmental constraints and associated stress we face later in life can also impact the rate at which we age. For instance, prolonged exposure to stress hormones are known to alter the hallmarks of ageing, but such knowledge mostly comes from in vitro cultured cells and laboratory studies of animals raised under non-challenging environmental conditions. Wether similar results will be found in wild animals that are constantly exposed to numerous stressors remains to be demonstrated, and for instance, we have evidence in several animal models suggesting that they evolved physiological mechanisms limiting the impact of environmental stress on ageing rate.
A minimally invasive way of studying mitochondria
Studying mitochondrial function has been restricted almost exclusively to the lab so far, most probably due to the necessity to obtain tissues such as liver, muscle or brain to perform measurements of mitochondrial respiration. While collecting such samples is most of the time impossible and undesirable in the wild, collecting blood samples is a procedure routinely used in many wild vertebrates. The vast majority (> 98%) of cells in the blood are red blood cells (RBCs), but while mammalian RBCs do not possess mitochondria, I demonstrated that avian RBCs retain functional mitochondria in their cytoplasm. This opens new perspectives for studying mitochondrial function in a minimally invasive way, which will be useful both in the lab and in the wild. For instance, this will allow measuring the same individual repeatedly, thereby boosting statistical power in ageing studies. This will also enable to establish links between mitochondrial function and life history traits such as growth rate, fecundity or lifespan in relationship to environmental conditions, which is essential to evaluate the role that mitochondrial function can play in shaping animal life histories.