Lingering senescent cells accumulate with age, and are one of the causes of aging. They secrete a potent mix of inflammatory signals that, while necessary to regeneration, suppression of cancer, and other requirements in the short term, are very damaging when sustained over the long term. Fortunately, most senescent cells are quickly destroyed, either by their own programmed cell death processes or by the immune system - though this degree of clearance is never perfect and seems to break down with age. It is thought that senescent cell levels climb quickly in later life because the immune system becomes dysfunctional, less effective at destroying errant and malfunctioning cells. In that light, this paper is interesting in that it finds only limited evidence of correlations between measures of senescent cell counts in skin and measures of immune system aging. One might expect there to be a more robust link here.
One of the processes hypothesized to underlie age-related functional decline in organ systems throughout the body is cellular senescence. This state of cell cycle arrest is believed to be irreversible under physiological conditions. In human skin, the prevalence of senescent cells is higher in aged individuals than in young. Previously, we observed that the number of skin cells positive for the cell cycle control protein p16INK4a, commonly accepted to be a marker of cellular senescence, was lower in offspring from long-living families and linked to cardiovascular disease. This suggests that skin aging occurs at a different pace in different individuals.
While the skin constitutes an important barrier, the immune system represents another organ system essential for protection against harmful environmental exposures throughout life. With age, several changes occur in the adaptive immune system, broadly termed immunosenescence. The number of naïve T cells decreases with age and differentiated memory, and effector T-cell numbers increase.
To study whether senescence occurs at the same pace in different organ systems, we studied 80 participants (aged 45-81 years) of the Leiden Longevity Study (LLS), assessing whether the amount of p16INK4a-positive cells in skin correlates with the amount of putatively immunosenescent T cells in blood. The mean age was 61 years, 48.8% were female, and half were seropositive for cytomegalovirus (CMV). Epidermal p16INK4a positivity was associated with neither CD4+ nor CD8+ T-cell immunosenescence phenotype composites, i.e., end-stage differentiated/senescent T cells. Dermal p16INK4a positivity was significantly associated with the CD4+, but not with the CD8+ immunosenescence composite. We therefore conclude that there is limited evidence for a link between skin senescence and immunosenescence within individuals.