Longevity Briefs: Is Depression An Age-Related Disease?

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.

Why is this research important: Globally, the incidence of depressive disorders is higher in older age groups. While this is not true for all subclasses of depression in all countries, depression among younger people seems to be more commonly driven by adverse life events. Depression in older people, on the other hand, is suspected to be linked to the ageing process itself. Factors like declining physical health, lack of quality sleep and onset of chronic medical conditions could all be contributing factors, but molecular changes in the brain and elsewhere could play a more direct role. There may also be a two-way relationship between depression and neurodegenerative disease.

What did the researchers do: In this study, researchers looked at data from 424,299 participants of the UK Biobank. Participants were middle aged and older, and their mental health status when they enrolled was known (based on hospital records and questionnaires). Participants also had their biological age measured using two different methods. As opposed to chronological age (years since birth), biological age is an estimate of how well someone’s body operates relative to the population average: if you have a biological age of 40, then your cells, tissues and organs perform more or less like those of the average 40 year-old.

Two algorithms were used to calculate biological age: the Klemera-Doubal method Biological Age (KDM-BA) and the PhenoAge algorithms. Both of these algorithms combine measurements of various blood markers as well as epigenetic changes in order to estimate biological age, though they are quite different in other ways. The main aim of the study was to see whether having a higher biological age at a given chronological age was associated with worse mental health.

Key takeaway(s) from this research: The researchers found that for both methods of measuring biological age, participants were significantly more likely to have anxiety or depression at the start of the study if their biological age was above average for their chronological age. Those who did not already have anxiety or depression were also more likely to develop one of those conditions over the next 9 years if their biological age was above average for their chronological age.

The strongest association was for depression with the PhenoAge algorithm: compared to the 25% of participants with the slowest rates of ageing (that is to say, the lowest biological age compared to their chronological age), the 25% with the highest rates of ageing were about 40% more likely to develop depression during the follow-up period. This was after researchers controlled for confounding factors like sex, smoking and chronic medical conditions. They also found that this increase in risk was independent and additive to genetic risk factors for depression. Having both a genetic predisposition to depression and accelerated biological ageing was associated with a 2.5 fold increase in depression risk (compared to slowly ageing, low genetic risk individuals).

This contributes more evidence to the idea that biological ageing promotes poor mental health, though we still don’t know exactly why. Changes within our cells (such as telomere shortening and deficient energy production) could contribute directly to diseases like depression. The link could also be more indirect, such as reduced quality of life due to general ageing, which is hard to quantify in studies. As is often the case when it comes to ageing, the answer is likely to be a combination of factors.