Longevity Briefs: Does ‘Love Hormone’ Oxytocin Slow Ageing?

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

The hormone oxytocin (OXT) is sometimes called the love or bonding hormone for its role in emotional connections. However, OXT isn’t just a ‘social’ hormone – it is important for reproduction, anxiety and stress reduction and metabolic function. Some evidence suggests that OXT levels may also play a role in the ageing process. Produced by a brain region called the hypothalamus, levels of oxytocin in the blood decline with age, but mouse studies suggest that administering oxytocin can reverse some signs of ageing, for example by improving muscle regeneration.

How might OXT be influencing the ageing process? In this study, researchers shed some light on the mechanism, which involves DNA methylation. Methylation is a form of epigenetic modification, in which molecular ‘tags’ called methyl groups are added to the DNA molecule in order to alter how the genetic code is read, without changing the code itself. Patterns of DNA methylation change with age, resulting in abnormal gene expression. One cause of this change involves enzymes called TET enzymes, which are important for removing methly groups from the DNA. The activity of TET enzymes declines with age.

The discovery:

Researchers compared young male mice (9 weeks old) to aged male mice (over 45 weeks, equivalent to around 35 human years). Consistent with previous findings, they observed that aged mice had lower OXT levels, as well as fewer OXT-producing neurons in the hypothalamus. These hypothalamus neurons also had significantly reduced levels of TET enzymes compared to those of the younger mice, as well as more poorly functioning mitochondria. Mitochondria are the power plants of the cell, responsible for generating ATP, the cell’s universal fuel. In this case, mitochondrial function was impaired because of reduced production of a key mitochonrdial enzyme called complex IV. TET enzymes are known to play a role here, as low TET enzyme levels can result in the methylation of the genes that encode mitochondrial enzymes, reducing their expression.

Researchers then tested whether administering OXT to aged mice would affect these measurements. They gave aged mice daily OXT treatments nasally for 10 days and found that this not only normalised OXT levels, but was also associated with increased OXT-producing neurons, increased TET enzyme levels, reduced inflammation and increased complex IV levels in the mitochondria compared to mice given a control treatment. Mice lacking the receptor for OXT showed similar defects to aged mice with low OXT levels, as well as accelerated signs of ageing.

The implications:

The study suggests that declining OXT levels may be contributing to a “vicious cycle” of ageing in which declining OXT levels reduce TET levels, leading to impaired mitochondrial function due to DNA methylation. Since impaired mitochondrial function negatively impacts most aspects of cellular function, this then leads to less OXT production by cells in the hypothalamus. Nasal OXT treatment can interrupt this cycle in animals by boosting TET expression and demethylating mitochondrial DNA. The restored OXT production could then have widespread beneficial effects such as in muscle regeneration as previously shown.

While promising, this research was conducted only in male mice with relatively small sample sizes (around 12 mice per group, depending on what was measured). In humans, OXT is known for its effects on childbirth and lactation, and has also been studied for its effects on mental health, but there is no evidence that it influences human ageing. More social activity is correlated with longer human life expectancy, so we could speculate that the mechanism discovered here might contribute to that relationship.