Monocytes Become More Inflammatory with Age
Monocytes of the innate immune system react to changes in the aging tissue environment by becoming more inflammatory. Those changes include the signaling of growing numbers of senescent cells, the presence of DNA debris from stressed cells, and the like. The innate immune system makes the issue worse by ensuring a state of chronic inflammation that disrupts normal tissue maintenance and function. Finding ways to suppress the inflammation of aging, such as the targeted removal of senescent cells, is an important goal in the treatment of aging as a medical condition.
It has been widely accepted that monocytes are one of the central mediators contributing to inflammaging. However, it remains unclear whether aged monocytes, similar to aged T cells, have characteristics of hyperactivation and increased expression of co-inhibitory molecules. Here, peripheral blood mononuclear cells (PBMCs) were isolated from young (21-40 years old), middle-aged (41-60 years old), and older human subjects (older than 60 years old). Flow cytometry was used to monitor changes in the expression of surface molecules of monocyte subsets and cytokine-producing capacity.
We observed increased TNF-α and decreased IL-6 production in monocytes from older adults compared with young and middle-aged adults. Older adults had a greater percentage of intermediate and non-classical monocyte subsets, along with increased levels of the immune activation markers HLA-DR, and adhesion molecules CD11b and CD62L. Furthermore, we observed increased CCR2 expression on classical monocytes and decreased CX3CR1 expression on non-classical monocytes in older adult subjects. The expression of co-inhibitory receptors was reduced on monocyte subsets in older adults.
In conclusion, circulating monocytes in older adults exhibit increased expression of activation, adhesion, and migration markers, but decreased expression of co-inhibitory molecules.
I am still not convinced, at least not 100 💯 %. That it is the monocytes themselves but not the whole agreed body environment which promotes inflammation so to increased burden in chronic infections, misfolded proteins, per cancerous cells and such. This type of environment might , in fact, "order" or promote producing of hyper inflammatory monocytes. And in some aspects, I suspect, it is a beneficial adaptation. Unfortunately if is far from perfect. On a world with sanitation, vaccination, antibiotics the above said adaptation might be overzealous.
P.s.
The more I read the more I am impressed that we puny humans can live well over middle age. There are so many things that gave to work in unison, and any one of them will inevitably break with time