The significant progress made by medical care in the last century has resulted in notable gains in life expectancy. However, increased life expectancy is not always matched with improved quality of life, indeed older people are more susceptible to chronic and debilitating diseases. Our lab is interested in investigating how we can improve cell resilience to aging and fitness, especially in the context of age-related metabolic dysfunction, such as type 2 diabetes.


To investigate how aging can impact cellular function at the molecular level, we use multiple experimental models, from cell lines to whole organism, including rodent and fish models. Although it might appear surprising, fish are physiologically and genetically similar to human, and they can be genetically engineered to model several diseases. Among fish models, African turquoise killifish are definitely one of the most interesting, because it is the vertebrate with the shortest lifespan recorded in captivity. During this short lifespan, the fish undergo many age-related physiological changes, such as neurodegeneration and cancer.


We seek to improve late-life health, by targeting the motor and energy source of mitochondria. This organelle has a crucial role in many cellular function, and it has been demonstrated that its activity declines with age and correlates with the progression of numerous diseases. However, it remains unclear what causes the decline of mitochondrial function through aging and we do not fully understand whether the rescue of dysfunctional mitochondria can counteract the detrimental consequence of aging.

  • Mitochondrial protein import

Mitochondria are an extremely “busy” organelle in the cell, but most of the proteins needed for mitochondria to function are encoded in the nucleus and imported from the cytosol. Many of these proteins aid in the fundamental mechanisms of mitochondria, including ATP generation, protection from oxidative stress and mitochondrial DNA replication. All nuclear-encoded protein traverse mitochondrial membrane(s) using dedicated import machinery, including the major complexes and memebrane translocase (i.e. TOM and TIM). This project is built on the hypothesis that the first symptoms of mitochondrial dysfunction are due to impairment of mitochondrial protein import.

  • Mitochondrial unfolded protein response

With impairment of mitochondrial transport, proteins that are normally translocated into mitochondrial can accumulate in the nucleus and induce the transcription of genes involved mitochondrial unfolded protein response (mtUPR). An examples is activating transcription factor (ATF)-5, which in normal conditions is targeted to mitochondria where it is degraded by the mitochondrial Lon protease. However, in the case of impaired mitochondrial protein import, ATF5 accumulates within the nucleus and ignites mtUPR. Many of the protein products are targeted to mitochondria, such as chaperones. The mechanism(s) which exclude ATF5 but allow for the import of chaperones are currently unknown.

  • Mitochondrial epigenetic regulation

Mitochondria synthetize by their own most of the proteins incorporated into the electron transport chain, motor and source of energy of this organelle. These proteins are encoded from the mitochondrial DNA (mtDNA), which is transcribed following mechanisms completely different from what regulates DNA transcription in the nucleus. Although, it has been extensively demonstrated that epigenetic regulation of nuclear DNA plays an important role in the change of gene expression through aging, as today there are no evidence whether age-related epigenetic modification occurs also in mitochondria. Our lab wants to first to challenge the existence of mitochondrial specific epigenetic regulation and then test whether it can be targeted to modify the course of aging in mitochondria.