The researchers here show an association between greater presence of advanced glycation end-products (AGEs) in skin and worse pulmonary function - which sounds plausible if we think of AGEs as a cause of loss of elasticity in tissues. Cross-links are formed by AGEs, and by linking and restricting the dynamics of structural proteins, they degrade the important structural properties of tissues, particularly elasticity. The details always bear examining however. In this study, the level of AGEs in skin was assessed using fluorescence, and based on the research of recent years, the important AGE when it comes to aging, glucosepane, is not fluorescent. Glucosepane forms truly persistent cross-links that human biochemistry struggles to remove, while other AGEs are transient in their effects, and more amenable to removal.
In people who do not have an abnormal metabolism characterized by raised levels of various AGEs, as is observed in diabetic patients, it is entirely plausible that glucosepane levels are fairly well correlated to levels of other, fluorescent AGEs. But it still makes this paper one that is most likely observing a relationship based on inflammation rather than structural properties: short-lived (and fluorescent) AGEs can induce inflammation via their interaction with RAGE, and this is one of the ways in which the abnormal diabetic biochemistry causes further harm, for example. There is a fair amount of evidence to suggest that chronic inflammation negatively affects pulmonary function. Now that it is possible to reduce inflammation by removing senescent cells, there is even data in mice to show that this reverses loss of lung tissue elasticity to some degree. Every decline in aging has multiple contributing factors.
According to recent studies, the level of advanced glycation end products (AGEs) increases with age and is higher in smokers and chronic obstructive pulmonary disease (COPD) patients. AGEs are bioactive molecules formed by the nonenzymatic glycation or peroxidation of proteins, lipids, and nucleic acids. AGEs increase inflammation by binding to receptors for AGE (RAGE), which are present on cell surfaces in tissues. Therefore, AGE accumulation may play a role in the pathogenesis of COPD by increasing inflammation. Several AGEs, such as pentosidine and Nε-(Carboxymethyl)-L-lysine (CML), have been reported to emit a characteristic fluorescence in human skin. AGEs assessed by skin autofluorescence (SAF) could help in the rapid evaluation of AGE accumulation in clinical settings.
Investigating factors associated with deteriorations in pulmonary function could help develop strategies to prevent the development of COPD in people with normal spirometry results, particularly given the serious impact of COPD on the risk of chronic disabilities and mortality. Therefore, we focused on the relationship between AGEs and pulmonary function in a general population with normal spirometry results. Moreover, given that aging is accompanied by an increase in AGEs and a decrease in pulmonary function, it would be informative to compare relationships between AGEs and pulmonary function in younger and elderly individuals. To this end, the present study aimed to evaluate the relationship between SAF and pulmonary function in younger and elderly people with normal spirometry results.
Two hundred and seventy-two males and females were enrolled in this study. Subjects underwent hematological examinations and additional assessments, such as the accumulation of AGEs in skin and pulmonary function. Subjects with an obstructive, restrictive, or mixed disorder pattern on the pulmonary function test were excluded. In addition, subjects with diseases that could influence pulmonary function (e.g., COPD, interstitial pneumonia, or asthma) or who received medications that could influence pulmonary function were excluded. Those with diabetes or hemoglobin A1c (HbA1c) higher than 6.5% were also excluded since diabetes and glycemic levels are known to be associated with both pulmonary function and level of SAF. The final study population consisted of 201 subjects (116 males).
We found that SAF is an independent factor negatively associated with the FEV1/FVC measure of pulmonary in elderly people with normal spirometry results, but not in younger people. Pack-years of smoking was a significant independent factor associated with FEV1/FVC in the elderly group. This study demonstrated that SAF is an independent factor associated with FEV1/FVC in the elderly group. According to other studies, AGEs in the blood and AGE accumulation in skin were higher in smokers than in non-smokers. AGEs can bind to and activate RAGE, which are present on cell surfaces in tissues, especially in the lung. Activation of RAGE increases inflammation via NF-κB. Therefore, the decrease in FEV1/FVC was likely accelerated by AGE accumulation.
With respect to the younger group, SAF was not associated with decreased FEV1/FVC. There are several potential explanations for the differences observed between the younger and elderly groups regarding factors associated with FEV1/FVC. First, the value of SAF is strongly related to age. In the present study, the value of SAF was significantly lower in the younger group compared to the elderly group. Therefore, inflammation resulting from AGEs might have been lower in younger subjects, resulting in the maintenance of FEV1/FVC. Second, the amount and/or activity of endogenous antioxidant enzymes between the two groups may have differed. It is well known that reactive oxygen species (ROS) can be buffered by endogenous antioxidant enzymes such as superoxide dismutase and catalase, and previous studies have demonstrated that levels of these antioxidant enzymes decrease with age.