How accelerated biological aging may cause bowel cancer
Study suggests that accelerated aging of an epigenetic clock may increase bowel cancer risk, with implications for developing ways to slow this process
Date:
March 29, 2022
Source:
eLife
Summary:
Scientists have shown how accelerated biological aging measured
by an epigenetic clock may increase the risk of bowel cancer,
according to a new report.
FULL STORY ========================================================================== Scientists have shown how accelerated biological aging measured by an epigenetic clock may increase the risk of bowel cancer, according to a
report published today in eLife.
==========================================================================
The study provides evidence that biological age might play a causal
role in the increased risk of certain diseases, and paves the way for interventions that could slow down this process.
Epigenetic markers are changes to DNA which may alter the way in which our genes work and are known to vary as we age. A type of epigenetic marker
called DNA methylation is often used to measure age. DNA methylation
patterns on the genome have been shown to relate closely with age and
they can provide insights into 'biological aging' -- that is, how old
our cells look compared to how old they are in years.
"When an individual's biological age is older than their chronological
age, they are said to be experiencing epigenetic age acceleration,"
explains first author Fernanda Morales-Berstein, a Wellcome Trust PhD
Student in Molecular, Genetic and Lifecourse Epidemiology at the MRC Integrative Epidemiology Unit, University of Bristol, UK. "Epigenetic
age acceleration, as measured by DNA methylation-based predictors of age
called epigenetic clocks have been associated with several adverse health outcomes including cancer. But although epigenetics can be used to predict cancer risk or detect the disease early, it is still unclear whether accelerated epigenetic aging is a cause of cancer." Making a causal link between biological clocks and disease is challenging because it is hard
to know whether biological aging increases the risk of disease, or whether other independent factors raise the risk of a disease and biological aging
at the same time. To address this, the team used a method called Mendelian randomization to mimic a randomized trial evaluating the effectiveness
of changes in epigenetic aging as a cancer prevention strategy.
They used information on known genetic variants associated with levels
of epigenetic age acceleration to investigate this.
The team compared four established epigenetic clocks used to measure
biological aging and their genetically predicted associations with
a range of cancer types. Two were first-generation clocks which use
patterns of DNA methylation strongly linked to chronological age. The
others were second-generation clocks which use markers associated with increased risk of age-related diseases or death.
They found limited evidence that accelerated epigenetic age is causally
linked to breast, lung, ovarian or prostate cancer.
The most striking result was seen for bowel cancer, where the results
measured by one of the second-generation clocks, called GrimAge,
suggested a 12% increased risk of bowel cancer with every additional year
of biological age (over chronological age). These results were further corroborated by an association between biological age acceleration and
parental history of bowel cancer. Further analysis suggested that evidence
for the risk was stronger for colon cancer compared with rectal cancer.
Previous studies have suggested that epigenetic age acceleration
is influenced by several cancer risk factors, such as obesity and
smoking. The additional evidence from the current study suggests
that targeting this pathway, for example through lifestyle changes or epigenetic-targeted therapies, could help reduce this risk.
"Our work provides potentially relevant findings for public health,"
says senior author Rebecca Richmond, Vice-Chancellor's Research Fellow
in Molecular Epidemiology at the MRC Integrative Epidemiology Unit,
University of Bristol.
"If epigenetic age acceleration is a causal mediator between risk factors
and bowel cancer, the clock may be a treatable intermediary for when
targeting the underlying risk factors is not feasible or too difficult
to accomplish, particularly in populations at high risk. More research
is needed to support our findings and evaluate whether epigenetic age acceleration can be modified by lifestyle or clinical interventions."
This research was funded by: Wellcome; Cancer Research UK; Medical
Research Council; Operational Programme 'Competitiveness, Entrepreneurship
and Innovation'; National Institute for Health Research (NIHR); NIHR
Biomedical Research Centres; University Hospitals Bristol and Weston NHS Foundation Trust; Alzheimer's Society; and National Institutes of Health.
========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
for style and length.
========================================================================== Journal Reference:
1. Fernanda Morales Berstein, Daniel L McCartney, Ake T Lu,
Konstantinos K
Tsilidis, Emmanouil Bouras, Philip C Haycock, Kimberley Burrows,
Amanda I Phipps, Daniel D Buchanan, Iona Cheng, Richard M Martin,
George Davey Smith, Caroline L Relton, Steve Horvath, Riccardo
E Marioni, Tom G Richardson, Rebecca C Richmond. Assessing the
causal role of epigenetic clocks in the development of multiple
cancers: a Mendelian randomization study. eLife, 2022; 11 DOI:
10.7554/eLife.75374 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220329114747.htm
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