Disentangling the effects of circulating IGF-1, glucose, and cortisol on features of perceived age

Circulatory levels of insulin-like growth factor (IGF-1), glucose, and cortisol have been previously associated with facial aging. However, as these serum measures are related, it is unclear whether their associations with skin aging occur independently from each other. We aimed to investigate whether the associations between serum IGF-1, glucose, and cortisol levels and perceived age/wrinkle grade occur independently of each other and whether these are mediated via skin wrinkling or via other skin aging features. Perceived age and skin wrinkling grade were assessed in a random sample from the Leiden Longevity Study with non-fasted (N = 579) and fasted blood sampling (N = 219). In our study population, a higher non-fasted IGF-1 level was associated with a lower skin wrinkling grade (p value = 0.014) and tended to associate with a lower perceived age (p value = 0.067), which was mediated for approximately 100 % by skin wrinkling. A higher non-fasted glucose level was associated with a higher perceived age (p value = 0.017), which was mediated for 51 % by skin wrinkling grade (p value = 0.112). A higher fasted cortisol level tended to associate with a higher perceived age (p value = 0.116), which was mediated for 29 % by skin wrinkling. Results remained similar when the serum measures were statistically adjusted for each other. Thus, the previously reported serum measures associate independently from each other with skin aging. IGF-1 is predominantly associated with perceived age by skin wrinkling, whereas cortisol and glucose also by other skin aging features.