Age-related impairments could be reversed

An international team of researchers has demonstrated in an animal model that two impairments of old age — frailty and immunity decline — can be halted and even partially reversed using a novel cell-based therapeutic approach. Their work has been published in the journal Nature Metabolism.

Elderly people are more prone to infectious diseases as the function of their immune system continuously declines with progression of age, as is apparent during outbreaks of seasonal influenza or other viral diseases such as COVID-19. The efficacy of vaccination in the elderly is similarly reduced, making this age group particularly vulnerable to infectious pathogens and having a high mortality rate. Aged individuals are also commonly affected by frailty that negatively impacts their quality of life, meaning that living longer is often associated with age-related health issues.

For many years scientists speculated that chronic low-grade inflammation accelerates ageing processes and the development of age-related disorders. The international research team has now demonstrated that visceral adipose tissue, known as belly fat, crucially contributes to the development of chronic low-grade inflammation. Led by Dr Mario Noti and Dr Alexander Eggel from the University of Bern, they showed that certain immune cells in the belly fat play an essential role in regulating chronic low-grade inflammation and downstream ageing processes — and that these immune cells may be used to reverse such processes.

The team demonstrated that immune cells known as eosinophils, which are predominantly found in the blood circulation, are also present in belly fat of both humans and mice. Although classically known to provide protection from parasite infection and to promote allergic airway disease, eosinophils located in belly fat are responsible for maintaining local immune homeostasis. With increasing age the frequency of eosinophils in belly fat declines, while the number of pro-inflammatory macrophages increases. Owing to this immune cell imbalance, belly fat turns into a source of pro-inflammatory mediators accumulating systemically in old age.

Detection of eosinophils in human visceral adipose tissue using two different staining methods; eosinophils are indicated with an arrowhead. AD: adipocytes. V: blood vessel. Image ©DBMR, University of Bern, D Brigger.

The researchers then investigated the possibility of reversing age-related impairments by restoring the immune cell balance in visceral adipose tissue. Dr Eggel revealed, “In different experimental approaches, we were able to show that transfers of eosinophils from young mice into aged recipients resolved not only local but also systemic low-grade inflammation.”

“In these experiments, we observed that transferred eosinophils were selectively homing into adipose tissue,” Dr Noti added. This approach had a rejuvenating effect on the aged organism; as a consequence, aged animals showed significant improvements in physical fitness as assessed by endurance and grip strength tests. Moreover, the therapy had a rejuvenating effect on the immune system manifesting in improved vaccination responses of aged mice.

“Our results indicate that the biological processes of ageing and the associated functional impairments are more plastic than previously assumed,” Dr Noti said. Importantly, the observed age-related changes in adipose immune cell distribution in mice were also confirmed in humans.

“A future direction of our research will be to now leverage the gained knowledge for the establishment of targeted therapeutic approaches to promote and sustain healthy ageing in humans,” Dr Eggel concluded.

Top image credit: ©stock.adobe.com/au/Africa Studio

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