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Studiegids

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Biological Mechanisms of Ageing and Development

Vak
2020-2021

Admission requirements

  • Biomedical Sciences: bachelor course Hormones and the nervous system

  • Successful completion of 3120321PPY (How to write a research proposal) is helpful, but not obligatory.

  • Successful completion of 312030400Y (CRiP – Advanced Concepts in R) is helpful, but not obligatory.

Description

Period: 21 September 2020 - 16 October 2020.

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 center on the hypothesis that the rate of ageing is determined by an intricate balance between damage accumulation and defense 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 strategies. Based on the central concept described above, this course focusses around five major themes, namely “The life course”, “Molecular damage control”, “Neuro-endocrine systems”, “Environmental cues”, and “Animal Studies: Methods and tools”.

The life course (week “0”; through self-study)
A life course perspective offers an interdisciplinary framework for guiding research on human ageing and vitality. The aim is to elucidate how interactions between various biological, behavioral, and psychosocial processes contribute to health and risk of disease across an individual’s life course. We will discuss what study designs have been used and developed in human research to observe or predict changes in health at different phases in life. Along the human life course, we will discuss hallmarks and determinants of the ageing process and the concept of biomarkers of disease and mortality risk. Furthermore, ageing and age-related diseases will be discussed from a gender and life course perspective.

Molecular damage control (week 1)
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. To deal with the different types of macromolecular damage, several dedicated systems for maintenance and repair have evolved. We will discuss which role(s) DNA repair mechanisms, the immune system, and metabolic stress response systems play in ageing and vitality.

Neuro-endocrine systems (week 2)
Evolutionarily conserved neuro-endocrine pathways have been identified in model organisms, whose modulation strongly impacts on longevity. In mammals, these include the somatotropic/ insulin/insulin-like growth factor-1 axis, the thyrotrophic axis, and the hypothalamic-pituitary adrenal (HPA) axis. 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 favorable conditions, available energy is readily invested in growth and development. Subtle changes in the setting of these neuro-endocrine pathways (which will determine how cues from the environment are perceived and integrated to provoke a coordinated response) can have great impact on lifespan. We will furthermore elaborate on how neuro-endocrinology, in the context of ageing, can be studied in human populations and in lower model organisms.

Environmental cues (week 3)
Depending on the environment and the stage of the life cycle, cues from the environment can have great impact on lifespan by changing the balance between energetic investments in maintenance and repair versus growth and reproduction. Such environmental cues include, amongst others, signals on the presence of potential mate(s), competitors, chemotoxic agents or pathogenic micro-organisms, and cues that convey information on nutrient availability, circadian time or seasonality

Animal Studies: Methods and tools (week 4)
The mission of the Max Planck Institute for Biology and Ageing in Cologne is to uncover the basic causes and processes of ageing. Also, they strive to understand the nature of longevity and age-related diseases. In this sense they aim for fundamental discoveries into the underlying molecular, physiological and evolutionary mechanisms. At the same time, it is investigated how the ageing process might be ameliorated to increase health during ageing in humans. Researchers from Max Plank will give lectures and will provide you with detailed information on the use of different animal models (e.g., mouse, C Elegans, D Molanogaster, killifish) in aging research.

Assignments
Self-study, assignments and exams. The exam will consist of an individually written Veni grant proposal, for research on the biological mechanisms of ageing (50% grade), the public defence of the grant proposal (10% of the grade), the scientific evaluation of three grant proposals written by peers (10% of the grade), and an individually written extended abstract on the results from a Mendelian Randomization practicum (10% of the grade), successful completion of the 4 week assignments (20% of the grade).

Competences
Research competences:
Literature research, writing and evaluation of a written grant proposal (defining a research question, choice of appropriate study design and techniques, description of expected results and impact), presentation skills, and a Mendelian Randomization workshop.

Professional competences:
Commitment, digesting other people’s opinions.

Course objectives

The student gets:

  • Insight in ageing and age-related diseases from a life course, gender and demographic perspective.

  • Insight in how repair and cellular defense mechanisms that evolved to protect the organism are related to the ageing process.

  • Insight in how neuro-endocrine mechanisms that evolved to facilitate adaptation of the organism to its changing environment are related to the ageing process.

  • Insight in how biological systems can be modulated by external factors.

  • Insight in the challenges and opportunities of doing research with model organisms in the study of vitality and ageing.

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

  • Writing and defending a condensed grant proposal on research in the field of ageing.

  • Scientifically evaluating three grant proposals written by peers.

  • In-dept discussions and presentations of an aging-related topic with 4 week assignments, related to the 4 week themes of the course.

  • Writing a condensed abstract about a Mendelian Randomization study in the field of ageing.

Timetable

All course and group schedules are published on our LUMC scheduling website or on the LUMC scheduling app.

Mode of instruction

Interactive lectures, tutor groups, self-study assignments.

Assessment method

Summative assessment:

  • Writing of grant proposal (VENI format)

  • Oral defence of grant proposal

  • Conduct peer evaluation

  • Abstract of a Mendelian Randomization study

  • Presentation

Reading list

Will be distributed during the course.

Registration

Registration for FOS courses, H2W, Scientific Conduct, How to start, Course on Animal Science, and CRiP and Adv concepts courses takes place in lottery rounds in the beginning of July. After the lottery rounds: if you want to register for a course you are kindly asked to contact the student administration at masterbw-courses@lumc.nl.

Contact

masterbms-courses@lumc.nl

Remarks

This course will be given in an online format.