Signaling from White Fat Tissue Contributes to Age-Related Hair Follicle Dysfunction
Changes in fat tissue behavior in the skin take place with age, such as rising levels of inflammation and inflammatory signaling. These changes have a detrimental effect on the ability of hair follicles to produce hair. The growth of hair is a complicated process that cycles through repeated phases of growth (anagen), transition (catagen), and rest (telogen). Aging leads to progressive dysfunction in this process and loss of hair in late life. A better understanding of the details of this dysfunction may lead to interventions, such as those attempted here in mice, to change the signaling of fat tissue in aged skin and thereby restore greater capacity to regrow hair.
Progressive deterioration in the regenerative potential of stem cells is a hallmark of aging, which results in the failure to maintain proper tissue homeostasis. Hair follicles are independent autonomous stem cell niches and undergo continuous regenerative cycling during their lifespan. With aging, hair follicle have diminished self-renewing capacity, manifesting as cycling defects and poor responsiveness to activating stimuli. hair follicle cycling slows down with aging and gradually turns into senescent alopecia.
Hair follicle stem cells are extensively reprogrammed by the aging process, manifesting as diminished self-renewal and delayed responsiveness to activating cues, orchestrated by both intrinsic microenvironmental and extrinsic macroenvironmental regulators. Dermal white adipose tissue (dWAT) is one of the peripheral tissues directly adjacent to hair follicles and acts as a critical macroenvironmental niche. dWAT directly contributes to hair follicle aging by paracrine signal secretion. However, the altered interrelationship between dWAT and hair follicle with aging has not been thoroughly understood.
Here, through microdissection, we separated dWAT from the skin of aged mice (18 months) and young mice (2 months) in telogen and depilation-induced anagen for transcriptome comparing. Notably, compared with young dWAT, aberrant inflammatory regulators were recapitulated in aging dWAT in telogen, including substantial overexpressed inflammatory cytokines, matrix metalloproteinases, and prostaglandin members. Nonetheless, with anagen initiation, inflammation programs were mostly abolished in aging dWAT, and instead of which, impaired collagen biosynthesis, angiogenesis, and melanin synthesis were identified. Furthermore, we confirmed the inhibitory effect on hair growth of CXCL1, one of the most significantly upregulated inflammation cytokines in aging dWAT.
Finally, we proved that relieving inflammation of aging dWAT by injecting high-level veratric acid stimulated hair follicle regenerative behavior in aged mice. Concomitantly, significantly decreased TNF-a, CCL2, IL-5, CSF2, and increased IL10 in dWAT was identified. Overall, the results elaborated on the complex physiological cycling changes of dWAT during aging, providing a basis for the potential regulatory effect of dWAT on aging hair follicles.