By
Michael Girling
MSc Human Evolution and Behaviour, 2023-24
The process of ageing is a universal phenomenon affecting all living organisms and recent research highlights how stress exposures within our environment possess the potential to accelerate the ageing process of our cells. To investigate this relationship, my research focused on the impacts of cumulative life stress exposures on epigenetic ageing in owl monkeys. This research stemmed from my interest of the ageing process particularly in neurodegenerative diseases and also the importance of non-human primates as models of disease and stress.
This research focused on the impacts of life stressors on the cellular (or biological), not the chronological, ageing process. Cellular age refers to how old your cells are based on physiological evidence whereas chronological age refers to how long you have existed.
To identify the cellular age of owl monkeys a measure of epigenetic changes was employed.
What is epigenetics?
Epigenetics refers to how certain environments and behaviours can alter how genes work, without changing the DNA/genes themselves.
One of the most researched epigenetic mechanisms is DNA methylation, which is the addition of a chemical group to DNA. There are different measures of DNA methylation, the measure used in this study was global DNA methylation which provides an overall look on epigenetic changes and was chosen because current research usually focuses on a genome-specific approach.
Global DNA methylation refers to the assessment of total 5-methylcytosine (5mC), which is the DNA nucleotide cytosine with an addition of a methyl group (CH3). 5mC is a common epigenetic modification and is also involved in cancer progression.
Changes in global DNA methylation were used a proxy of epigenetic ageing in this study.
Why owl monkeys?
Owl monkeys (aka Night monkeys) are nocturnal New World monkeys of the genus Aotus. They were chosen for this research as they are especially susceptible to environmental stressors.
In particular, my research focused on IVITA’s captive colony of owl monkeys from Peru. Owl monkeys are known to be rejected by their mothers and are primarily cared for by their fathers. Furthermore, as with other non-human primates, due to their genetic closeness to humans, they are a good model of disease and stress.
Therefore, blood and brain DNA samples of the IVITA owl monkeys were used.
The methodology of my research
An ELISA 5mC kit was used which enabled the analysis of the percentage of methylated cytosine content in the brain DNA samples.
Colorimetry, which is the science of the measurement of colour, was then used to quantify the levels of 5mC (the percentage of cytosine content).
Documents of infection, rejection and offspring were then incorporated into the statistical analyses.
The findings of my research
My research examined blood and brain DNA samples from the IVITA Owl monkeys. In particular the percentage of global DNA methylation in the samples.
The findings supported the fact that global DNA methylation is strongly correlated with ageing. Global DNA methylation decreases with age.
Blood and the brain were found to age differently in which brain samples had higher amounts of global DNA methylation. This was expected due to the evolution of the larger primate brain and indicates that blood would not be good to use as an indicator of epigenetic ageing of the brain.
Various life stress exposures were then factored; maternal rejection (being rejected by their mothers), infection history, and having offspring.
Despite previous research linking childhood adversity to accelerated epigenetic ageing, maternal rejection didn’t affect ageing. Similarly, infection history wasn’t shown to affect ageing despite other research showing distinct global DNA methylation differences in afflicted subjects.
However, owl monkeys who had four or fewer offspring were found to have accelerated ageing in comparison to those with five or more offspring. Stress exposures’ were not found to influence reproductive success although stressed owl monkeys were predicted to have no offspring (decreased reproductive success) more so than those not stressed.
Furthermore, sons were not found to have higher energetic costs (epigenetically) when compared to daughters. Similarly, no acceleration of ageing was associated with rates of reproduction in older females.
While the individual stress exposures showed no effect on the ageing process, their combined effect was shown to accelerate the ageing process.
The implications of the research
This research revealed the influences of evolutionary factors, such as the larger primate brain and favouring reproduction over own cellular maintenance on epigenetic ageing.
Furthermore, this research showed the impact of different life stressors on epigenetic ageing. In particular, the combination of life stress exposures including early life stress with maternal rejection, history of infection, and varying number of offspring, accelerate the (cellular) ageing process in owl monkeys.
This study needed more brain samples and more blood samples in order to confirm the association between global DNA methylation and ageing.
Future research should therefore focus on the combined effect of stress exposures, along with exploring additional stress factors. Analysing the stress hormone cortisol to gain further knowledge is essential, and a comprehensive approach should be used, considering both long-term effects and any potential transgenerational impacts.
