95 research outputs found
Genetic and DNA methylation markers of ageing muscle
Inter-individual variation can be found in muscle mass and strength during the
ageing process, and in muscular adaptations to exercise. These inter-individual
differences are related to genetic and DNA methylation factors. Therefore, the
objective of this thesis is to explore the role of underlying genetic polymorphisms
and DNA methylation with muscle strength and mass in an ageing population. This
thesis first evaluated the overall genetic association with changes in muscle mass
and strength among older adults (n = 200, 60β83 yrs) who received a one year of
training and were reassessed one year after the cessation of training. The genetic
profile was represented as a data-driven genetic predisposition score (GPS), which
was calculated based on muscle-related genetic variants selected from 170
candidates through stepwise regression. The results showed that a data-driven GPS
explained 0.7% of the variance in skeletal muscle mass (SMM) and 3.2% of the
variance in knee strength at baseline level, 14% of the variance in SMM and 27%
of the variance in knee strength after the training, and 27β37% of the variance in the
loss of muscle mass and strength after the one-year cessation of training. The thesis
further compared differences in blood sample methylation patterns between
sarcopenic and non-sarcopenic women (n = 48, 65β80 yrs). 6,258 differentially
methylated CpGs (dmCpGs) that had different methylation levels (p < 0.01) between
the sarcopenic and non-sarcopenic groups were identified. Genes containing these
dmCpGs were involved in multiple biological pathways that were related to muscle
function, actin cytoskeleton regulation and energy metabolism. A DNA methylation
profile score was calculated as a weighted sum of methylation levels of sarcopeniadriven CpG sites (MSSAR, based on sarcopenia-related lasso logistic regression)
and the MSSAR was negatively associated with vastus lateralis size, elbow and
knee strength, and explained 10.1%, 35.5% and 40.1% of the variance, respectively.
In conclusion, this thesis shows that both genetic sequence architecture and DNA
methylation play a role in explaining the inter-individual differences in muscle mass
and strength in older adults. An individual with a more favourable genetic profile
might have not only greater baseline muscle strength, but also a higher probability
to respond well to training and a smaller muscular loss after quitting the training.
This study provided new insights in how the methylation status differ between weak
older women compared to generally age-matched muscularly fit women. Using
easily accessible blood samples, individuals at high risk of sarcopenia might be
identified based on their methylation profile
Robust estimation of large factor models for tensor-valued time series
In this paper, we consider inference in the context of a factor model for
tensor-valued time series. We study the consistency of the estimated common
factors and loadings space when using estimators based on minimising quadratic
loss functions. Building on the observation that such loss functions are
adequate only if sufficiently many moments exist, we extend our results to the
case of heavy-tailed distributions by considering estimators based on
minimising the Huber loss function, which uses an -norm weight on
outliers. We show that such class of estimators is robust to the presence of
heavy tails, even when only the second moment of the data exists
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