A PhD position is available for a collaboration between
the Laboratory of Prof. Marco Demaria at the ERIBA, part of the UMC Groningen (UMCG), the Netherlands and the laboratory of Prof. Lene Juel Rasmussen at the CEHA, part of the University of Copenhagen (UCPH). The project is focusing on the role of mitochondria in age-associated senescence.
Aging is associated to a widespread deterioration of the functional capacities of an organism. Among major regulators of tissue integrity and dysfunction are mitochondrial activity and cellular senescence. Tissues with high metabolic activity are more susceptible to mitochondrial dysfunction. Decline in mitochondrial function provokes a decline in nicotinamide adenine dinucleotide (NAD+) levels, notably affecting the activity the NAD+-dependent sirtuins. This dysfunction may also lead to increased inflammation, as well as altered apoptosis and disrupted crosstalk among organelles. Cellular senescence represents a state of stable proliferative arrest triggered by damaging signals which include mitochondrial dysfunctions. Senescent cells acquire peculiar characteristics, such as a hypersecretory phenotype (SASP). The SASP contributes to tissue deterioration and chronic inflammation, eventually supporting the progression of age-related disease and dysfunctions. Oxygen partial pressure (pO2) varies profoundly between and within organs and mammalian cells have evolved programmed responses to oxygen concentrations. These pathways have profound effects on mitochondria and senescence-associated features.
The goal of this project is based on findings originating in the two laboratories and is to define how oxygen-dependent mitochondrial modulations affect the physiological and pathological function of senescent cells during aging and disease. Specific objectives are:
- to identify mitochondrial perturbations that affect the senescence phenotype upon oxygen oscillations;
- to monitor the relationship between mitochondrial activity, cellular senescence and longevity;
- to investigate the mitochondrial-driven mechanisms promoting pro-aging features in senescent cells.