Recently, murine studies have reported the increased expression of programmed cell death-1 (PD-1) receptor specifically on exhausted CD8+ effector memory T cells with low levels of CD28 showing limited proliferative and cytokine-producing capacity.36 As the increased expression of PD-1 is likely due to chronic activation of the immune system from lifelong latent infection associated with ageing and frailty, further work on the identification of a CD8+CD28− coupled with PD1+ positivity as a replicative senescence phenotype in frailty may be fruitful. This evidence concerns the gene CD8A and disease arising from reactivation of latent virus.