Age-related immune decline reversed in mice

Researchers have established the cause of a worsening immune system with increasing age and demonstrated this can be halted using a novel therapeutic approach

As people age, they experience a gradual decline in immune function and become increasingly prone to infectious diseases. We know this just by looking at seasonal influenza outbreaks or the recent COVID-19 viral disease which manifests particularly brutally in elderly people. Not only is this due to the natural worsening of immune function, but the efficacy of vaccinations becomes greatly reduced in elderly people, meaning they are left particularly vulnerable to these sorts of infections.

For many years, scientists have suspected that the process of ageing and development of age-related disorders is fuelled by chronic low-grade inflammation. Researchers have recently confirmed these suspicions and found that it is visceral adipose tissue (belly fat) which exacerbates this inflammation.

Belly fat and inflammation

Eosinophils are a type of immune cell which are largely found within the blood, but are also present in visceral adipose tissue. Here, they help sustain local immune homeostasis and control obesity-related inflammation and metabolic disease. As people age, the number of eosinophils in adipose tissue decreases, and these cells are replaced by pro-inflammatory macrophages. These macrophages are another type of immune cell which promote the body-wide accumulation of pro-inflammatory mediators, leading to the chronic low-grade inflammation seen in old age.

Eosinophil cell therapy

Seeing the effect of this immune cell disbalance, researchers from the University of Bern explored the idea of reversing age-related immune system decline by restoring the correct number of eosinophils in adipose tissue. Experimenting on mice, the researchers found that transplanting eosinophils from young mice into aged mice reversed both local and body-wide low-grade inflammation. As a result, the immune system of the mice was restored and the mice showed an improved response to vaccination.

The findings of this study have significant meaning for the clinical scenario. The age-related shift in adipose immune cell distribution in mice can also be seen in humans, which means the transfer of eosinophils into elderly people may one day become a novel therapy to prevent immune system degradation. Whilst the elderly remain one of the most vulnerable groups in society, the development of this sort of targeted therapy could significantly reduce the risk of infectious diseases in older people and prevent the stark fatality numbers as we currently see with COVID-19.

Reference:

  1. Daniel Brigger, Carsten Riether, Robin van Brummelen, Kira I. Mosher, Alicia Shiu, Zhaoqing Ding, Noemi Zbären, Pascal Gasser, Pascal Guntern, Hanadie Yousef, Joseph M. Castellano, Federico Storni, Neill Graff-Radford, Markus Britschgi, Denis Grandgirard, Magdalena Hinterbrandner, Mark Siegrist, Norman Moullan, Willy Hofstetter, Stephen L. Leib, Peter M. Villiger, Johan Auwerx, Saul A. Villeda, Tony Wyss-Coray, Mario Noti, Alexander Eggel. Eosinophils regulate adipose tissue inflammation and sustain physical and immunological fitness in old age. Nature Metabolism, 2020; DOI: 10.1038/s42255-020-0228-3
  2. Chih-Hao Lee. Young eosinophils rejuvenate ageing adipose tissues. Nature Metabolism, 2020; DOI: 10.1038/s42255-020-0230-9

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