Can accelerated biological aging explain cognitive decline in schizophrenia?

However, schizophrenia is not only associated with psychiatric symptoms; recent reports indicate that people with schizophrenia have a significantly shorter life expectancy (up to 15 years) and increased risk of age-related diseases, such as heart disease and dementia, compared to unaffected, similarly aged peers.

This has led to the proposed theory that individuals with schizophrenia might experience “accelerated aging”. One of the ways of determining this is through the study of a cell’s ability to replicate, most commonly measured through the length of a part of the human chromosome known as the telomere.

Telomeres in schizophrenia

Imagine our chromosomes as shoestrings, comprised of a thread and a protective cap. If the cap wasn't present, the shoestring would begin to fray. Whilst initially not a significant problem, over time our shoestring would become too short for us to effectively lace up our shoes, leading to the shoe itself being un-wearable. A similar process occurs in human cells, with the shoestring representing DNA and the protective cap representing the telomere, whose main job is to protect DNA.

Telomeres naturally shorten as we age – called telomere attrition – and can only be regrown to a certain extent. As a result, when a critical telomere length is reached, that specific cell will stop dividing. Over time, this leads to the body not being able to as effectively rejuvenate damaged tissues and organs, leading to the development of various diseases.

In our recent study, we aimed to explore whether changes in telomeres and their maintenance could explain the cognitive impairments observed in individuals with schizophrenia. We utilised a cohort of 758 participants collected as part of the Norwegian Thematically Organised Psychosis (TOP) Study, with all participants undergoing a cognitive assessment of several domains commonly affected in psychosis (for example, memory, learning and processing speed), as well as providing us with a blood sample.

The blood sample was used to compare telomere length and the genetic expression of two genes which make up telomerase, the enzyme responsible for telomere repair (called Telomerase Reverse Transcriptase – TERT, and Telomerase RNA Component - TERC). We also calculated two ratios related to the maintenance of telomeres (TERT-to-Telomere & TERC-to-Telomere).

Our findings

Our results indicated that individuals with schizophrenia had shorter telomeres as well as lower genetic expression of TERT, which is crucial for helping telomeres to repair. If we revert back to the shoestring analogy, this means that the protective cap (the telomere) is not able to protect the shoestring (the DNA) effectively, and is also not able to repair due to the reduced TERT.

Additionally, people with schizophrenia had higher telomere repair ratios compared to healthy controls. This suggests that the body is trying to utilise all available TERT and TERC to stave off accelerated telomere shortening.

On the other hand, we did not find a strong connection between telomere length, TERT or TERC and cognitive functioning (e.g., memory, processing speed and learning). This may suggest that while telomere biology may play a role in the general aging process in schizophrenia, it might not be the main driver of cognitive decline.

Why does this research matter?

Our research adds another piece to the puzzle that is schizophrenia, helping build a more complete picture of how this complex condition impacts the body. By learning more about such cellular processes, we will hopefully not only better understand the mechanisms leading to psychosis development, but also develop treatments addressing the broader health challenges faced by people living with schizophrenia.

It is of course imperative for future research to explore how external factors - such as stress, inflammation and general lifestyle - influence telomere biology in schizophrenia. Moreover, determining how such cellular aging markers change over time in response to treatment or disease progression is another avenue worth investigating.

Conclusion

Schizophrenia is often thought of as a purely mental health disorder, but our research shows that its effects extend to the very core of cellular aging. While telomere biology does not seem to explain the cognitive impairments observed in psychosis, it offers a glimpse into the complex interplay between mental illness and physical health.