Prospectus

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Biological Mechanisms of Ageing and Development

Course 2011-2012

Admission requirements

  • Master Vitality and Ageing: master course The Ageing process
  • Biomedical Sciences: bachelor course Hormones and the nervous system
  • Medicine: bachelor course The Ageing Process
    Successful completion of 3120321PPY (How to write a research proposal) is helpful.

Description

Period:

Sept 26 – Oct 21, 2011

Week 1: neuro-endocrine regulation of longevity
In the first week, we will focus on gene and environment interactions and on the neuro-endocrine regulation of longevity. Evolutionarily conserved pathways have been identified in model organisms, whose modulation strongly impacts on longevity, including signal pathways that work through insulin/insulin-like growth factor-1 and receptors for nuclear hormones, such as the thyroid hormones. These pathways play an important role in adapting the organism to its changing environment. Under adverse conditions, such as infection or starvation, growth and development are generally suppressed and available energy is preferentially invested in maintenance and repair to cope with these and anticipated future challenges, while under favourable conditions, available energy is readily invested in growth and development. Thus, cues from the environment, but also subtle changes in the setting of these pathways (which will determine how cues from the environment are perceived and integrated to provoke a coordinated response) can have great impact on lifespan.

Week 2: genomic instability
In the second week, we will focus on the importance of genomic instability for ageing. Persistent damage will interfere with the functionality of different macromolecules and disrupt the integrity of cells, tissues and the organism. To deal with the many different types of macromolecular damage, several dedicated systems for maintenance and repair have evolved. The biological significance of these many DNA repair mechanisms is highlighted by their evolutionarily conservation and by the phenotypes of patients with inherited defects in DNA repair genes. Strikingly, defects in DNA repair mechanisms can be associated with very different clinical phenotypes, including cancer and (premature) ageing. The persistence of mutagenic lesions will put cells at a higher risk of neoplastic transformation, while the persistence of cytotoxic lesions will lead to the induction of apoptosis and/or senescence. While cellular senescence and apoptosis protect individuals from cancer in their reproductive years, these processes may also lead to the exhaustion of the number of division-competent stem cells. Moreover, senescent cells can become resistant to apoptosis and secrete proteins such as metalloproteases, inflammatory cytokines and growth factors that may destroy the local tissue structure, attract cells that cause inflammation and stimulate neighbouring cells to proliferate, thus enhancing the risk of late life cancer.

Week 3: calorie intake
In the third week, we will focus on the effect of calorie intake on human ageing and life span. It is thought that the current epidemic of obesity is one of the major health threats and may accelerate ageing and age-related diseases. Interestingly, from the perspective of the biology of ageing, experiments involving calorie restriction (CR) in rodents in 1935 provided the first promise for modulation of life span. Calorie restriction, i.e. limitation of food intake without malnutrition, has been shown to extend life span in every organism that has been tested to date, including yeast, worms, flies and rodents and most likely also non-human primates. Importantly, lifespan extension produced by CR is associated with delayed onset, reduced incidence and reduced severity of age-associated diseases and with preservation of a “youthful” phenotype. In the fourth week, we will discuss the potential of clinical applications of CR in humans.

Week 4: research proposal
Self study, assignments and exams. The exam will consist of an individually written grant proposal, the public defence of the grant proposal and the scientific evaluation of two grant proposals written by peers.

Competences

Research competences:

Writing a grant proposal: defining a research question, choice of appropriate study design and techniques, description of expected results and impact.

Professional competences:

Commitment, digesting other people’s opinions.

Course objectives

  • The student has insight in the concept of gene by environment interactions
  • The student will be able to explain how neuro-endocrine mechanisms that evolved to facilitate adaptation of the organism to its changing environment are related to the ageing process.
  • The student will be able to explain how repair and cellular defense mechanisms that evolved to protect the organism against genomic instability and cancer are related to the ageing process.
  • The student has insight in the role of calorie intake on ageing and age-related diseases and its potential for therapeutic interventions.
  • The student will be able to exploit his/her knowledge on the biology of ageing by writing and defending a condensed grant proposal on research in the field of ageing.

Mode of instruction

Interactive lectures, workgroups, self study assignments.

Assessment method

  • During the course students will write 3 short summaries on different topics
  • Writing of grant proposal (Veni format)
  • Oral defence of grant proposal
  • Evaluation of two grant proposals written by peers
  • Student behaviour (motivation, independency, oral reporting, participation in discussion)