Age-related impairments reversed in animal model

Date:
July 6, 2020
Source:
University of Bern
Summary:
Frailty and immune decline are two main features of old
age. Researchers now demonstrate in an animal model that these two
age-related impairments can be halted and even partially reversed
using a novel cell-based therapeutic approach.



FULL STORY ========================================================================== Elderly people are more prone to infectious diseases as the function of
their immune system continuously declines with progression of age. This
becomes especially apparent during seasonal influenza outbreaks or the occurrence of other viral diseases such as COVID-19. As the efficacy
of vaccination in the elderly is strongly reduced, this age group is particularly vulnerable to such infectious pathogens and often shows the highest mortality rate. In addition to the age-related immune decline
aged individuals are commonly affected by frailty that negatively impacts quality-of-life. Even though the average life- expectancy for humans
continuous to rise, living longer is often associated with age-related
health issues.


========================================================================== Important role of belly fat in aging processes identified Researchers
from the Department for BioMedical Reserarch (DBMR) and the Institute of Pathology at the University of Bern as well as the University Hospital
Bern (Inselspital) have set out to identify new approaches to improve health-span in a fast-growing aging population. For many years scientists speculated that chronic low-grade inflammation accelerates aging
processes and the development of age-related disorders. An international
team of researchers under Bernese guidance has now demonstrated that
visceral adipose tissue, known as belly fat, crucially contributes to the development of chronic low-grade inflammation. Scientist around Dr. Mario
Noti, formerly at the Institute of Pathology of the University of Bern
and Dr. Alexander Eggel from the Department for BioMedical Research
(DBMR) of the Universita"t of Bern reported that certain immune cells in
the belly fat play and an essential role in regulating chronic low-grade inflammation and downstream aging processes. They could show, that these
immune cells may be used to reverse such processes. The findings of this
study have been published in the scientific journal "Nature Metabolism"and
were further highlighted by a News and Views editorial article.

Belly fat as a source of chronic inflammation The team around Dr. Noti and
Dr. Eggel could demonstrated that a certain kind of 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 to maintain 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 dysbalance, belly fat turns into a source of pro-inflammatory mediators accumulating systemically in old age.

Eosinophil cell therapy promotes rejuvenation In a next step, the
researchers investigated the possibility to reverse age- related
impairments by restoring the immune cell balance in visceral adipose
tissue. "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," says
Dr. Eggel. "In these experiments, we observed that transferred eosinophils
were selectively homing into adipose tissue," adds Dr. Noti. 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.

Translating findings into clinics "Our results indicate that the
biological processes of aging and the associated functional impairments
are more plastic than previously assumed," states Dr.

Noti. 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 aging in humans," says Dr. Eggel.


========================================================================== Story Source: Materials provided by University_of_Bern. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Daniel Brigger, Carsten Riether, Robin van Brummelen, Kira
I. Mosher,
Alicia Shiu, Zhaoqing Ding, Noemi Zba"ren, 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 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200706140905.htm

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