Nature sub-journal Research Tips: Why Older People Are More Susceptible to Influenza

Although the COVID-19 pandemic provided a brief respite, the flu virus has returned to circulating and poses a particular danger
to people over the age of 65 as usual.
But why are older people more susceptible to the flu? A new study published in the journal Nature Communications at the University of Michigan School of Medicine provides clues
.

The study was led by first author Judy Chen, Ph.
D.
, Ph.
D.
, senior author Daniel Goldstein, MD, professor of internal medicine and professor of microbiology and immunology in the Maria Mosher School, and their team investigated why alveolar macrophages, the lungs' first line of defense, are damaged
with age.

These macrophages are immune cells that attack invaders, such as the flu virus, small air sacs or alveoli
that live inside the lungs.
Importantly, these cells seem to disappear
with age.

Previous research by another team has shown that when macrophages from older mice are implanted into young mice, the cells look young again
.
"This leads us to believe that something in the lung environment is responsible for this," Chen said
.

There are indications that a lipid immunomodulator called prostaglandin E2 (PGE2) has a wide range of effects, from induction of labor in pregnancy to arthritis inflammation
.
The team found that the amount of PGE2 in the lungs increased
with age.
Chen explained that the increase in PGE2 acts on macrophages in the lungs, limiting their overall health and ability to
produce.

The team suspects that the accumulation of PGE2 is another marker of a biological process known as aging, which is often age-related
.
Aging is insurance against uncontrolled division of damaged cells; Senescent cells are no longer able to replicate
.

"Interestingly, these cells secrete a lot of inflammatory factors.
"

Studies have shown that as we age, the cells of the air sacs in the lungs begin to age, and these cells cause increased production of PGE2 and suppress the immune response
.

To test the link between PGE2 and increased susceptibility to influenza, they treated old mice
with a drug that blocks the PGE2 receptor.
"Older mice injected with this drug actually have more alveolar macrophages and have better survival rates from influenza infection than older mice that were not injected with this drug
," Chen said.

The team plans to next investigate the various ways PGE2 affects lung macrophages and its potential role
in systemic inflammation.
"As we age, we are more susceptible not only to the flu, but also to other infections, cancers and autoimmune diseases
.
"