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Biological Mechanisms of Ageing and Development

Vak 2018-2019

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: 24 September 2018 - 19 October 2018

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 five major themes, namely “Molecular damage control”, “Neuro-endocrine systems”, “Environmental cues”, “Enhancing vitality” and “The life course”.

Molecular damage control (week 0: through self-study)
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 1)
Evolutionarily conserved neuro-endocrine pathways have been identified in model organisms, whose modulation strongly impacts on longevity. In mammals, these include the somatotrophic/ insulin/insulin-like growth factor-1 axis, the thyrotrophic axis, and the hypothalmamic-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 favourable 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 2)
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.

Enhancing vitality (week 3)
It is thought that the current epidemic of obesity is one of the major health threats and may accelerate ageing and age-related diseases, including different neuro-degenerative 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 brain health. In this course, we will discuss the preventative and therapeutic potential of applications such as diet and nutrition, physical activity and neuropeptides in different groups of older humans, including patients.

The life course (week 4)
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, behavioural, 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.

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 (62.5% grade), the public defence of the grant proposal (12.5% of the grade), the scientific evaluation of three grant proposals written by peers (12.5% of the grade), and an individually written extended abstract on the results from a Mendelian Randomization practicum (12.5% 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, Mendelian Randomization practicum/workshop, teaching activities in working group sessions with minor/Master students Vitality and Ageing.

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

Course objectives

The student gets:

• Insight in how repair and cellular defense mechanisms that evolved to protect the organism against genomic instability and cancer 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 the potential for (therapeutic) interventions to modulate lifespan and enhance vitality.
• Insight in ageing and age-related diseases from a life course perspective.

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.
• Communicating and applying knowledge from lectures and literature in a working group session with minor and Master students – Vitality and Ageing.
• Writing condensed abstract about a small research project 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.

Course load

Total course load is the amount of EC’s multiplied with 28 hours.

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

Blackboard

Blackboard will be used during this course.

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