Introduction to Development and Ageing Flashcards
NOTE: this isn’t necessary to learn, it is just an introduction
Development and ageing: opposing trends
- Spike after WW2 and baby boom in 1960
- precipitous decline in the 70s (birth control pill invented in 1961) and stayed at this low level for about the last 30 years or so
- Study predicts global fertility rate is going to decline quite dramatically. In next 50 years or so it is predicted that actually we are going to see a decline in global population so from 9 billion to around 8.8 billion and this is driven by the falling birth rate as women are having less children
- Need to have 2 live births per women to prevent a decline in population
-As we move into 2030s the proportion of people over 65 is going to increase as whole population is shifted to older years. And this is where disease burden is great in these ages, we see a sharp increase in DALYs. Population is getting older-social issues of how does younger population support increasingly aged population and also the increase in disease.
In 2016 there is relatively homeogeneous distributions of aged populations but moving forward, a much greater proportion of people will be included in these age 65+ pockets.
Each different colour is a different disease and as we move past 50 and 60 there is a large increase in DALY
-Older population which experiences greater proportion of disease and at the same time at a social point of view, there are fewer younger people of working age to pay and support them.
Ageing and Development domain: aims
- How does embryo-fetal development underpin adult disease?
- How do environmental impacts during early life events influence lifelong health?
- How we can promote health ageing?
Fertilisation
Occurs in antrum of fallopian tube.
Development of Conceptus
- Continues to divide as it moves down Fallopian tube to uterus (3-4 days)
- Receives nutrients from uterine secretions
- This free-living phase can last for ~ 9-10 days
Implantation
•Attachment phase: outer trophoblast cells contact uterine surface epithelium
THEN
- Decidualisation phase : changes in underlying uterine stromal tissue (within a few hours)
- Requires progesterone domination in the presence of oestrogen
Attachment
- Leukaemia inhibitory factor (LIF) from endometrial cells stimulates adhesion of blastocyst to endometrial cells
- Interleukin-11 (IL11) also from endometrial cells is released into uterine fluid, and may be involved
- Many other molecules involved in process (e.g. HB-EGF)
Phase 1b Development and Ageing: TILOs
extrauterine environment-things that happen outside uterus to mother eg pesticides or smoking which can then affect the embryo/foetus.
Decidualisation
- Endometrial changes due to progesterone
- Glandular epithelial secretion
- Glycogen accumulation in stromal cell cytoplasm
- Growth of capillaries
- Increased vascular permeability (→oedema)
- Factors involved:
- Interleukin-11 (IL11), histamine, certain prostaglandins & TGFb (TGFb promotes angiogenesis)
Why study development? Understanding birth defects
-slightly more common in males we think, even when we correct for sexual development.
Why study development? Understanding birth defects
-As mothers get older, the risk of having a birth defect increases exponentially. In this case in trisomy but almost all birth defects follow this pattern.
This is a challenge because we know that the age in which women have children is also increasing (red dotted line). Fraction of women having first child over 30 has tripled over 30 years.
Chromosomes in oocyte are held together by proteins called cohesins and these don’t get replaced, so over 50 year span before menopause, glue that holds together chromosomes can decrease and then when miosis restarts the chromosome can fall apart.
Paternal increasing age is more related to neurological defects eg autism and schizophrenia.
Why study development? Understanding cancer
Apoptosis-regulating organ size and getting rid of finger webbing
Migration-eg neurocrest, Gastrulation
So cell has to be responsive to get these signals
Cancer cells mirror these processes
By understanding normal biological processes in development, can start to understand the factors that underpin cancer.
Why study development? Insight into common/ chronic diseases
If take patients with hypertension and non hypertensive controls, we can see patients with hypertension have half as many glomeruli.
Tissue repair potential as we could use stem cells to recreate normal embryo development and then perhaps work out how to reverse problems that go wrong.
Why study development: fetal origins of adult disease
Correlation between birth weight and cardiovascular disease in lower weight.
DNA is wrapped around histones and epigenome can modify the histones to make them wrap more tightly or not and also methyl groups can attach directly to the DNA to have an effect.
Why study development:
Fetal orgins of adult disease
- Level of cortisol that foetus sees
- High fat, low protein diet can influence health in adulthood
- Offspring of mothers who smoke have fewer eggs and shorter reproductive window and also men have a lower sperm count.
Think this occurs due to epigenetic changes, particulraly on methyl groups on DNA which are responsible for switching genes on and off.
Why study development: child development
gross motor-crawl and walk
fine-grasp and use pencil etc
These things can all be tracked by schemes eg Denver 2 which has a series of milestones to measure how children are developing.
Development and Ageing: Phase 1b summary
Dev & Ageing: Teaching and links to other topics
