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Biological Mechanisms of Ageing and Development

Vak 2014-2015

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 22 – Oct 17, 2014

Ageing can be described as “a progressive, generalized impairment of function, resulting in an increasing vulnerability to environmental challenge and a growing risk of disease and death”. Although the pathologies that accompany ageing are diverse and the rate at which it occurs differs widely between species, the universality of the ageing process suggests that common biological mechanisms may be at play. Many of the prevailing proximate theories of ageing centre on the hypothesis that the rate of ageing is determined by an intricate balance between damage accumulation and defence and repair mechanisms. From this hypothesis, it follows that analysis of the mechanisms by which this balance is regulated may reveal the regulatory axes of the ageing process and allow the development of anti-ageing therapeutics. Based on the central concept described above, this course focusses around three major themes, namely “Damage and repair and ageing”, “Neuro-endocrine regulation of lifespan” and “Modulation of lifespan”. Diverse topics related to these three themes will be discussed on the Mondays and Tuesdays during the first three weeks of the course. Fridays will be devoted to tutor groups to discuss progress in the writing of an individual Veni grant proposal for research on the biological mechanisms of ageing.

Damage and repair and ageing
There are strong evolutionary arguments that ageing is not programmed, but instead occurs in an evolutionary shadow. Due to evolved limitations in the systems for maintenance and repair, stochastic damage to vital macromolecules will accumulate over a lifetime, leading to a gradual functional decline. Persistent damage will interfere with the functionality of different macromolecules and disrupt the integrity of cells, tissues and the organism. We will discuss the contribution of reactive oxygen species (ROS) and mitochondrial mutations to the accumulation of macromolecular damage. To deal with the different types of macromolecular damage, several dedicated systems for maintenance and repair have evolved. We will discuss which role DNA repair mechanisms, stem cells and telomere shortening play in the balance between damage accumulation and defence and repair mechanisms.

Neuro-endocrine regulation of lifespan
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 and corticosteroids. 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. Such cues also include light/dark cycli.

Modulation of lifespan
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 provided the first promise for modulation of life span. 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 this course, we will discuss the potential of applications related to maintenance of energy homeostasis such as diet, physical activity and facultative thermogenesis in humans as well as ways to interfere with the central regulation of feeding behaviour and metabolic control and stem cell based therapies.

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 three 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 following three themes of the biology of ageing:

  • how repair and cellular defence mechanisms that evolved to protect the organism against genomic instability and cancer are related to the ageing process.
  • how neuro-endocrine mechanisms that evolved to facilitate adaptation of the organism to its changing environment are related to the ageing process.
  • the potential for therapeutic interventions to modulate the rate of ageing.

The student will be able to exploit his/her knowledge on these three themes of the biology of ageing by:

  • writing a condensed grant proposal on research in the field of ageing
  • scientific evaluation of three grant proposals written by peers

Mode of instruction

Interactive lectures, workgroups, self study assignments.

Assessment method

  • Writing of grant proposal (Veni format)
  • Oral defence of grant proposal
  • Evaluation of three grant proposals written by peers
  • Student behaviour (motivation, independency, oral reporting, participation in discussion)