Aging immune system (immunosenescence) and the skin

A well-established feature of physiological ageing in the
skin is an impaired epithelial barrier function. More
“danger” signals will then easily enter the skin and quickly
be noticed by the innate immune cells in the skin. The
functional integrity of the immune system during the
natural course of aging is an important issue. There is
an accumulating body of evidence that a decline in immune
function with age is common to most if not all vertebrates.
Almost all of the immune system components
undergo an aging-related alteration, thus impacting the
innate and adaptive immunity. The age-related decline in
the normal functions of immune system is referred to by
the specific term “immunosenescence” and is believed to
be associated with diminished abilities to induce protective
immunity, diminished vaccine efficacy, increased incidence
of cancer, autoinflammation and autoimmunity,
and the impaired ability to generate tolerance to harmless
antigens. The mediators produced by innate immune
cells, specific cytokines and chemokines, are increased
with increasing age, especially proinflammatory cytokines
such as interleukin (IL)-6, IL-1b, TNF-alpha, while
the number and the function of the neutrophils are unaltered.
On the other hand there is also an increase with
age in NK cells. This chronic sub-inflammation, often observed
in the elderly is called inflammaging. The gradual
weakening of the immune system begins around the age
of 60 and gradually deteriorates with age . Age-associated
thymic involution seems to occur in all species that possess
a thymus. However, the exact order and precise cellular
changes that occur between individuals can be diverse,
due to differences in environmental exposures and genetic
composition. One important potential mechanism underlying
immunosenescence includes epigenetic changes
such as changes in DNA methylation (DNAm) and DNA
hydroxymethylation that occur with age. Ageing is associated
with numerous changes in immune cell subsets,
antigen-specific cells and cytokines, consistent with an
increasing acquisition of a Th2-cell bias. There is a trend
towards a lower Th1 : Th2 ratio. Cell subset analysis consistently
demonstrated an increase in Th2 cells in both
sexes with increasing age. Decreases in the total number
of T cells and naive T cells in males and females in addition
to decreases in T helper cells and cytotoxic T cells in
males have been observed. This ageing- associated cellular
Th2 bias explains why an autoimmune skin disease as
bullous pemphigoid and chronic pruritus in the elderly
predominantly occur in elderly people. In conclusion, remodelling
of the immune system with increasing age, immunosenescence,
is characterized by a sort of immunodeficiency,
low‐grade chronic systemic (auto)inflammation
and increased risk of autoimmunity.