It is well established that long term exposure to forms of air pollution increases the risk of mortality and numerous age-related conditions. The mechanisms of interest revolve around increased systemic chronic inflammation that is provoked by the interaction of pollutants, such as fine particles, with airway and lung cells. Is this exposure and its consequences a form of accelerated aging? The question of whether one environmental factor or another accelerates aging forces us to consider how aging is defined and measured. Hitting people with hammers repeatedly will certainly increase mortality, and may even increase common measures of biological age, such as epigenetic clocks, but is it producing accelerated aging? One can debate the question, but clearly more biological data would be needed to actually answer it. Looking only at mortality or loss of function is insufficient, one has to also think about what is going on under the hood in the biochemistry of cells.
In today's open access paper, researchers correlate forms of air pollution, several different measures of biological age, and dementia risk. The greater the exposure to air pollution, the greater the increase in biological age measures and the greater the risk of dementia. Under the hood, there is more inflammation, a greater burden of senescent cells, and likely other features of aging to a greater degree. Biological age measures such as epigenetic clocks tend to obscure all of that, however. Senescent cell burden is perhaps a helpful way to think about the effects of exposure and whether those effects are in fact accelerating aging. Senescent cells accumulate with age, and the more there are the worse the outcome. They are a form of damage that negatively impacts tissue structure and function over time. We might consider any exposure that robustly increases senescent cell burden to be creating accelerated aging; consider obesity, for example, or chemotherapy. There are numerous other forms of aging-associated cell and tissue damage that we can measure, and to the degree that they are increased, we can suggest that this increase reflects an increased biological age.
Air pollution is globally ubiquitous and has been identified as a risk factor for global disease burden. Limited epidemiological studies have linked air pollution to morphological brain alterations, with inconsistent findings, and most of them have focused only on a single type of regional brain region. Furthermore, although air pollution has been established as a risk factor for dementia, the underlying neurobiological mechanisms are poorly understood. Recent evidence suggests that air pollution may accelerate systemic biological aging.
Given that dementia is fundamentally an age-related neurodegenerative disorder, accelerated biological aging is a plausible, upstream mediator in the pathway from air pollution exposure to dementia. Since individuals age at different rates, quantifying biological aging rather than chronological age may reveal a more precise mechanistic link between exposure and health outcomes. Together, we propose a novel mechanistic hypothesis: exposure to air pollution may first accelerate systemic biological aging, which in turn drives the degeneration of specific brain structures, ultimately leading to the onset of dementia.
Therefore, using data from the UK Biobank, we aimed to: (1) examine the associations of long-term exposure to five air pollutants (PM2.5, PM10, PM2.5 absorbance, NO2, and NOx) with global gray/white matter volumes, 80 regional gray matter volumes, and incident dementia; (2) assess the association between biological age acceleration and both air pollution and incident dementia; and (3) investigate the mediating roles of biological aging acceleration and brain structure alterations underlying the air pollution-dementia association.
Cox proportional hazards regression models were used to evaluate the association between air pollution and incident dementia, while linear regression models were used to assess its associations with global and 80 regional brain structures. The mediating roles of biological aging acceleration (measured by Klemera-Doubal method Biological Age [KDM-BA] and PhenoAge) and brain structures in the air pollution-dementia association were evaluated using structural equation modeling (SEM).
Compared to participants with the lowest tertile of air pollution exposure, those in the highest exposure group had higher risks of dementia (Hazard ratio, HR: 1.141 for PM2.5; 1.09 for PM10; 1.09 for PM2.5 absorbance; 1.20 for NO2; and 1.14 for NOX). Air pollution exposure was inversely associated with global and several regional brain structural alterations. SEM revealed a consistent mediating pathway that integrates biological aging and brain structural alterations in the association between air pollution exposure and the risk of dementia.
View the full article at FightAging
