As people get older, they tend to have more infections, to develop more diseases (such as cancer) and to be less responsive to vaccination. Many people consider this as a natural consequence of the ageing process. However, the latest scientific results in that domain show that at least parts of the ageing occurring in the immune system might actually be reversible (1-3).
The principal fighters against infections in our body are a subset of immune cells called T-cells, which make up part of the white blood cell population. T-cells proliferate at every infection in order to get rid of the infectious agent. However, with each cell division, defects are accumulated in the new daughter cells, and the telomeres of the chromosomes (which are DNA sequences situated at the end of a chromosome and meant to protect the latter from deterioration) are shortened. With time, T-cells become dysfunctional, which participates to the age-related decline of immunity. It has also been shown that those senescent T-cells get depleted of mitochondria, which are the energy plants of the cells (2).
Researchers have discovered a way to reverse ageing in those immune cells, namely by blocking a particular signaling pathway called the p38MAPK pathway. P38MAPK is a molecule that, when activated through phosphorylation, can trigger senescence by blocking some cellular processes. In effect a study led by Prof Arne Akbar at the University College London, showed that inhibition of p38MAPK signaling in senescent T-cells increased their proliferation, telomerase activity, mitochondrial biogenesis, and fitness (1).
In another study, the same research team found that p38MAPK activated itself when aging was coupled with low nutrient supply (2). This is of predominant importance since it points out to the fact that the same pathway is regulated by both nutrient supply and damages occurring in the cells as a result of senescence. The most important consequence is that the opening of a new way of action for nutrition as immunity booster as an alternative of drug-manipulation of the immune system, which is the approach extensively used nowadays.
This is the first time that researchers have shown tangible evidence of a link between ageing and metabolism in immune cells. This new perspective paves the way towards diet-mediated modulation of immunity, in particular to block or reverse the age-related decline of immunity, through especially adapted diet or innovative diet supplementations such as micronutritional combinations.
1. Henson SM, Lanna A, Riddell NE, Franzese O, Macaulay R, Griffiths SJ, Puleston DJ, Watson AS, Simon AK, Tooze SA and Akbar AN (2014) p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells. J Clin Invest 124: 4004-16 2. Lanna A, Henson SM, Escors D and Akbar AN (2014) The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells. Nat Immunol 15: 965-72 3. Di Mitri D, Azevedo RI, Henson SM, Libri V, Riddell NE, Macaulay R, Kipling D, Soares MV, Battistini L and Akbar AN (2011) Reversible senescence in human CD4+CD45RA+CD27- memory T cells. J Immunol 187: 2093-100