New findings recently published in Nature Immunology and in the Journal of Clinical Investigation show that we can now mitigate the unfortunate deactivation of elderly immune systems by inhibiting a specific pathway and via nutrition.
This question is a serious one because with age, our immune systems become less effective, the mechanism of which is based less on the shortening of the white blood cells telomere than on an evolutionary white blood deactivation resulting both from the increased number of years on planet Earth and the nefarious consequences of infections among the elderly. (1)
In a new study published in Nature Immunology, scientists show that p38 MAPK (the white blood cell brake) is activated by low nutrient levels, coupled with signals associated with age, or senescence, within the cell, in particular the T lymphocytes. (2)
The second paper, published in The Journal of Clinical Investigation, (3) showed that blocking p38 MAPK with existing P 38 inhibitors boosted the fitness of cells that had shown signs of ageing, improving the function of mitochondria (the cellular batteries) and enhancing their ability to divide. (4)
Cellular senescence has essentially been characterized as the irreversible loss of proliferative capacity despite continued viability and metabolic activity (5). This arrested cell division arises as a consequence of either telomere-dependent or telomere-independent pathways, the latter being induced as a result of DNA damage by reactive oxygen species (ROS) or the activation of cellular stress pathways (5, 6) and aggravated via inflammatory inflammatory cytokines, inter alia (7). Thanks to these two combined studies, we now better understand immune-senescence’s mechanisms of action, much of which can be impacted by nutrition and lifestyle medicine (See the Pyrenean Center for Holistic Wellbeing’s optimal longevity program).
(1). In this light, Research has unmasked many years ago the deleterious impact of infections upon the aged. Each time an elderly person recovers from an infection, a proportion of his or her white blood cells become deactivated. This is why it is important to help the elderly avoid infections in the first place, so that the white blood cells will be activated enough to carry out other tasks, including but not limited to anti cancer surveillance and control.
(2). See: “The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells”, by Lanna et al, published in Nature Immunology. This study was conducted by researchers from UCL, Cancer Research UK, University of Oxford and University of Tor Vergata, Rome, Italy.
In previous BBSRC funded work, Professor Arne Akbar’s group at UCL showed that aging in immune system cells known as ‘T lymphocytes’ was controlled by a molecule called ‘p38 MAPK’ that acts as a brake to prevent certain cellular functions. They found that this braking action could be reversed by using a p38 MAPK inhibitor, suggesting that the rejuvenation of old T cells is possible.
See also: D. Di Mitri, R. I. Azevedo, S. M. Henson, V. Libri, N. E. Riddell, R. Macaulay, D. Kipling, M. V. D. Soares, L. Battistini, A. N. Akbar. Reversible Senescence in Human CD4 CD45RA CD27- Memory T Cells. The Journal of Immunology, 2011
(3) See: J Clin Invest. 2014;124(9):4004–4016. Published in Volume 124, Issue 9 (September 2, 2014). “p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells”, by Sian M. Henson 1, Alessio Lanna 1, Natalie E. Riddell 1, Ornella Franzese2, Richard Macaulay 1, Stephen J. Griffiths 1, Daniel J. Puleston 3, Alexander Scarth Watson 3, Anna Katharina Simon 3, Sharon A. Tooze 4 and Arne N. Akbar1 (1 Division of Infection and Immunity, University College London, London, United Kingdom. 2 Department of Systems Medicine, University of Tor Vergata, Rome, Italy. 3 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom. 4 Secretory Pathways Laboratory, London Research Institute, Cancer Research UK, London, United Kingdom. Address correspondence to: Sian M. Henson, Division of Infection and Immunity, University College London, 5 University Street, London, WC1E 6JF, United Kingdom. Phone: 220.127.116.119; E-mail: firstname.lastname@example.org. Source)
(4). Extra energy for the cell to divide was generated by the recycling of intracellular molecules, a process known as autophagy. This highlights the existence of a common signaling pathway in old/senescent T lymphocytes that controls their immune function as well as metabolism, further underscoring the intimate association between ageing and metabolism of T lymphocytes.
(5). Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8(9):729–740.
(6). Passos JF, Von Zglinicki T. Oxygen free radicals in cell senescence: are they signal transducers? Free Radic Res. 2006;40(12):1277–1283.
(7). Coppe JP, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol. 2008;6(12):2853–2868.