Longevity Briefs: Extracellular Vesicles Improve Memory In Elderly Monkeys

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:

Working memory is like the mental notepad for holding and manipulating information in the short term – when you have to remember a verification code just long enough to type it in, for example, you are using working memory. Working memory progressively declines with age, and this is largely the result of damage to white matter. White matter is composed of neurons that are sheathed in a protective coating called myelin, which allows electrical impulses to travel faster along their nerve fibres. There are various reasons for the loss of myelin with age, including increased damage from sources like inflammation, and a reduced ability to repair myelin due to a decline in the number of cells able to develop into myelin-producing oligodendrocyes.

One potential strategy for regenerating myelin has been to introduce stem cells that would then develop into the necessary cell types to initiate repair. However, researchers have recently discovered that stem cell-derived extracellular vesicles (EVs) – tiny membrane packages containing genetic information and signalling molecules – appear to be responsible for a surprisingly large number of the benefits offered by stem cells themselves. Compared to stem cells, EVs have the advantage of being much easier to manufacture and store, and are also likely to be safer than stem cell therapies. In this study, researchers investigate whether EVs are able to protect white matter and improve cognitive function in ageing rhesus monkeys.

The discovery:

Researchers found that regular administration of stem cell-derived EVs was correlated with better cognitive performance and improved white matter structure and function.

Researchers gave biweekly (every two weeks) injections of EVs to 17-24 year-old rhesus monkeys, which are considered ‘late middle-aged’. The EVs in question were derived from mesenchymal stromal cells (MSCs) isolated from the bone marrow of young monkeys. MSCs are a type of stem cell capable of differentiating into multiple different cell types and commonly used in research.

The study used 13 monkeys in total, split into one group that received MSC-EVs intravenously and another group that received a control infusion. Researchers then tracked their performance in various cognitive tasks, and also measured brain white-matter structure and function using magnetic resonance imaging (MRI). At the end of the treatment period, which lasted 18 months, the MSC-EV–treated monkeys showed significantly improved spatial working memory and fewer ‘perseverative errors’ (repeatedly making the same incorrect responses) compared with controls, while recognition memory (the ability to remember whether an object had been encountered before) wasn’t substantially changed. MRI scans suggested that treated monkeys had improved white-matter integrity and inter-connectivity compared to controls.

The implications:

This study suggests MSC-EVs may slow or partly reverse some aspects of age-related cognitive decline by protecting or restoring white-matter integrity and preserving functional network connections. For human longevity and brain health, the findings are encouraging – monkeys are close to humans evolutionarily and have relatively long lifespans in comparison to other research animals. And while stem cells are mostly unable to cross from the blood and into the brain, extracellular vesicles do not have such issues, meaning that, unlike stem cells, they do not need to be injected directly into the brain.

On the other hand, receiving an infusion of extracellular vesicles every two weeks would still be a relatively arduous and expensive undertaking, and is currently beyond the means of all but the wealthiest medical tourists. Even if EVs were more accessible, they are still in the early phases of human testing for the treatment of specific diseases, and while they are likely to be safer than stem cells, their long-term safety in humans still isn’t well established.