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Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Telomeres: protective caps of chromosomes
- Telomere DNA sequences in different species
- Vertebrate telomere structure and telomerase
- Telomeres and cellular ageing
- Ageing is the body ‘wearing out’
- Telomeres and monogenic disease
- Role of genes in disease
- Dyskeratosis congenita (DKC)
- DKC is caused by mutations in telomere proteins
- Hoyeraal-Hreidarsson syndrome
- Age of onset of telomere syndromes
- Werner syndrome
- Telomeres and ageing
- Telomeres shorten with age
- Studying LTL in the northern Finland birth cohorts
- Leukocyte telomere length (LTL) in NFBC 1966
- Multiple factors influence telomere length
- Unemployment and telomere length in NFBC1966
- Long term unemployment → shorter LTL (in men)
- Short telomeres and stressful life experiences
- Prenatal factors and telomere length
- Dot plot illustrating LTL
- Telomeres and cardiovascular disease
- Telomere length and age-related conditions
- Telomeres and cardiovascular disease studies
- Short telomeres and coronary heart disease
- Short telomeres and cardiometabolic disorders
- Telomere length and cardiovascular disease risk
- Genetic factors associated with telomere length
- Single Nucleotide Polymorphisms (SNPs)
- Homozygotes and heterozygotes
- How many SNPs?
- Studying SNPs
- Genome-Wide Association Studies (GWAS)
- GWAS for quantitative traits
- Correcting for multiple testing
- GWAS results as a “Manhattan” plot
- Common genetic variants associated with LTL
- Telomere maintenance genes
- Genetics can help investigate causality
- LTL may play a causal role in CAD
- Telomere length risk of cardiovascular disease
- Telomere shortening cause age-related disease?
- Telomere shortening and age-related disease
- CVD and atherosclerosis
- LTL and CVD risk
- Age of onset of telomere syndromes in patients
- Telomeres, Atherosclerosis and human longevity
- Summary
Topics Covered
- Vertebrate telomere structure and telomerase
- Telomeres and monogenic disease
- Telomeres and ageing
- Factors that affect leukocyte telomere length (LTL)
- Telomere length and stressful life events
- Telomeres and cardiovascular disease risk
- Common genetic variants associated with LTL
- A causal role for LTL in CVD: evidence and potential mechanisms
Links
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Talk Citation
Buxton, J. (2018, July 31). Telomeres and cardiovascular disease [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 9, 2024, from https://doi.org/10.69645/UHQR3630.Export Citation (RIS)
Publication History
Financial Disclosures
- Dr. Jess Buxton has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Clinical Practice
Transcript
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0:00
I'm Dr. Jess Buxton,
I'm a geneticist at University College London.
This talk is on the role of "Telomeres and Cardiovascular Disease".
0:11
I'll start with an outline of what telomeres are,
and the role of the enzyme telomerase in telomere function before
covering telomeres and their role in monogenic disease and their role in
normal aging and then the rest of the talk will focus on the role of telomeres and in
particular telomere length and its role in risk of cardiovascular disease.
0:32
So, what are telomeres? Well,
they're the protective caps found at the ends of all linear chromosomes,
in this picture here they've been stained with a fluorescent dye.
0:43
So, telomeres are composed of repetitive sequences of DNA,
these are all G rich but are different in different species.
In jellyfish it's TTAGGG and that
also happens to be the same as all vertebrates including humans,
but it's not just one copy of this repeat unit it's
many thousands and it's there to act as a buffer to protect the coding sequences.
Every time a cell divides,
it will lose a little bit of the DNA from the ends of
all its chromosomes because of the way DNA is replicated.
The cell's DNA replication machinery can't
quite copy to the end of one half of the double helix strand,
so a little bit is lost,
this is known as the end replication problem.
So, to prevent this eroding the coding sequences,
the genes and regulatory sequences,
the telomeric DNA is there and acts as a buffer so
that is lost rather than the coding sequences in the rest of the chromosome.
1:38
So, in vertebrates including humans,
telomeres are composed of many units of the six base pair repeat
TTAGGG bound to a complex of proteins known collectively a shelterin,
six core proteins and several additional proteins,
as you can see in this diagram.
Shelterin serves to protect the telomeric DNA and prevent the cells
DNA repair mechanisms from recognizing
the ends of linear chromosomes as double-stranded DNA breaks.
So, they prevent chromosome fusion.
So, in addition to their buffering function whereby every time
a cell divides a little bit of the telomeric DNA is lost,
with the addition of the shelterin complex it's also preventing fusion,
so they're preventing both degradation and fusion.
So, telomeres are absolutely crucial for genomic integrity of the cell.
So, as I've mentioned in most cells,
every time the cell divides in most tissues,
the telomeres we'll get a little bit shorter every time.
This isn't the case in some cell types particularly germ cells and stem cells,
where an enzyme called telomerase is able to replace
telomeric DNA repeats and it does this using its own RNA template.
It's unusual enzyme that it's composed of
both an RNA molecule known as TERT which provides a template to
add on additional telomeric DNA repeat units
and the TERT protein which is a reverse transcriptase.
It's active in germ cells and stem cells to maintain the telomeres in those cell types.
Telomerase is also reactivated in around 90 percent of cancer cells and this is how
cancer cells become immortal and don't
die out and become senescent as other cell types do.