New research reinforces the possibility that exosomes derived from stem cells can bring the body back in to a more healthful, youthful state.

Two recent publications highlight the growing relevance of exosomes to aging. One report highlights that aging of humans is associated with an accelerating decline in the concentration of circulating exosomes. The second report shows in mice that aging is at least partly controlled by exosomes from brain cells and that aging can be slowed and lifespan extended by adding exosomes by infusion.
We now know it works in mice [1] and initial clinical studies are beginning to show promise in people that exosomes will be effective therapeutic agents against age-related disease (see http://exopharm.com/news/2017/06/20/exosomes-versus-stem-cells/)

Youth on tap ?
The number of extracellular vesicles (EVs) that naturally circulate in the human body declines significantly with aging, research published in the Nature journal Scientific Reports has shown [2]. As we age, we become more susceptible to a wide range of diseases, from heart attack and stroke to Alzheimer’s and other neurodegenerative diseases. A growing number of recent studies have shown that EVs including exosomes – nanoscale packets of biomolecules including proteins and RNA, naturally released by various cells in the body – play a central role in maintaining health.

But until now, no study had taken a longitudinal look at the changes of EV levels to individual humans in different age-groups and over time. Nicole Noren Hooten from the National Institute on Aging (NIA) in Maryland, US, and her colleagues have now taken the first step to filling this knowledge gap. Studying 74 healthy individuals in three age segments (around 30 years of age, around 50 years of age and around 60 years of age), the researchers compared each individual’s EV levels in two blood samples taken 5 years apart. The researchers saw a clear decline in levels of circulating EVs with age, and where the oldest group shows the sharpest decline. They also noted significant differences in the way older individuals’ EVs were taken up by immune cells and altered their behaviour. These reports add weight to the growing list of evidence that infusions of regenerative exosomes could help to counter many age-related diseases, for example by restoring circulating exosomes levels to a more youthful state.

In the latest example, published in Nature in July, researchers showed infusions of exosomes slowed down aging in mice [1]. The exosomes were collected from a particular population of stem cells produced by the hypothalamus, a region of the brain previously implicated in aging. Middle-aged mice receiving the hypothalamic neural stem cells, or the exosomes the release, lived longer and showed fewer age-associated disorders than their untreated peers.

Reducing inflammation is healthy 
When it comes to aging, it’s not simply the number of EVs in circulation around the body that changes, the NIA researchers reported. The type of EV in circulation, and their influence on the other cells, also changes as we age, they discovered. This leads to the idea that there can be “good” EVs and “bad” EVs – and that aging is linked to a decrease in good EVs and an increase in bad EVs. The team showed that some EVs isolated from older subjects were more readily taken up by immune cells called B cells. These cells are the body’s antibody-producing factories, essential for fighting off infections. The researchers also showed that these aged or bad EVs more effectively activated a second type of immune cell called monocytes, a type of white blood cell. The findings tie in with the fact that aging in general, and age-related disease in particular, is associated with chronic inflammation, a condition linked to overactive immune system that results in systemic stress and impaired self-repair around the body. “This data suggests that bad EVs may transmit inflammatory signals to immune cells, which may in turn continue the inflammatory cascade,” the team reported in the paper. Administering more “good” EVs might be a mechanism by which aging could be reversed.

Biomarker Central
Another implication of the work is that EVs would appear to be excellent potential biomarkers of overall health in aging humans. Patterns of EVs levels in the blood could become a convenient way to get a quick and non-invasive read-out of an individual’s well-being. Several previous studies have also reported a significant shift in EVs numbers associated with various specific age-related disease including cancer and Alzheimer’s.
There is more research to be done on exosomes and aging, and many details to be filled in. But the paper’s headline finding that EVs decline with age and appear to promote chronic inflammation all add weight to the idea exosomes derived from stem cells, with their proven regenerative effects, could put the body into a more youthful state primed for healing…

References
[1] – Zhang, Y. et al. Hypothalamic stem cells control ageing speed partly through exosomal miRNAs. Nature (2017), doi: 10.1038/nature23282
[2] – Eitan, E. et al. Age-Related Changes in Plasma Extracellular Veiscle Characteristics and Internalization by Leukocytes. Scientific Reports 7, 1342 (2017)