Skin immunity as a function of frailty, aging, and skin microbiome composition

PROJECT SUMMARY / ABSTRACT The goal of this proposal is to profile skin immunity and infection response in aging as a function of the skin microbiome. Older adults have increased susceptibility to a wide range of skin-related adverse events, including bacterial, fungal, and viral skin infections that can progress to serious systemic infection, skin cancer, and reduced quality of skin health, including skin barrier function. Different constituents of the skin microbiome modulate the development and maintenance of cutaneous innate and adaptive immunity. Physical changes in skin structure not only change the environment conducive to microbial colonization, but also changes the penetrance of its products to impact local immune function. We recently found that the skin microbiome remodeled dramatically not so much with chronological age but with frail aging, and we hypothesize that FADS interacts with cutaneous immunity to reduce skin health and responsiveness to infection. In Aim 1, we will define aging of cutaneous immunity by evaluating skin immunity, using an innovative microneedle sampling device, as a function of skin microbiome and frailty in 120 healthy younger adults, healthy older adults, and frail older adults. In Aim 2, we will use Diversity Outbred mice to model human population-level genetic diversity to investigate aging of cutaneous immunity and infection response, modeling microbial depletion, microbial colonization with healthy and frailty-associated human microbiota, and treatment with senolytics and anti- inflammatories. This work will define how the skin immune cell populations differ in aging and unhealthy aging, and how the skin microbiome differentially primes skin immunity in aging. These data provide the foundation for pinpointing influential microbes and immune interactions that may be modulated as a therapeutic or prophylactic approach, as well as identify risk factors for a range of skin disorders in older adults.