Naslov
Epilipidomics of Senescent Dermal Fibroblasts Identify Lysophosphatidylcholines as Pleiotropic Senescence-Associated Secretory Phenotype (SASP) Factors

Autori
Narzt, Marie-Sophie ; Pils, Vera ; Kremslehner, Christopher ; Nagelreiter, Ionela-Mariana ; Schosserer, Markus ; Bessonova, Emilia ; Bayer, Alina ; Reifschneider, Raffaela ; Terlecki- Zaniewicz, Lucia ; Waidhofer-Söllner, Petra ; Mildner, Michael ; Tschachler, Erwin ; Cavinato, Maria ; Wedel, Sophia ; Jansen-Dürr, Pidder ; Nanic, Lucia ; Rubelj, Ivica ; El-Ghalbzouri, Abdoelwaheb ; Zoratto, Samuele ; Marchetti- Deschmann, Martina ; Grillari, Johannes ; Gruber, Florian ; Lämmermann, Ingo

Izvornik
Journal of Investigative Dermatology (0022-202X) 141 (2021), 4; 993-1006e15

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
fibroblast, senescence-associated secretory phenotype, stress-induced premature senescence

Sažetak
During aging, skin accumulates senescent cells. The transient presence of senescent cells, followed by their clearance by the immune system, is important in tissue repair and homeostasis. The persistence of senescent cells that evade clearance contributes to the age- related deterioration of the skin. The senescence- associated secretory phenotype of these cells contains immunomodulatory molecules that facilitate clearance but also promote chronic damage. Here, we investigated the epilipidome—the oxidative modifications of phospholipids— of senescent dermal fibroblasts, because these molecules are among the bioactive lipids that were recently identified as senescence-associated secretory phenotype factors. Using replicative- and stressinduced senescence protocols, we identified lysophosphatidylcholines as universally elevated in senescent fibroblasts, whereas other oxidized lipids displayed a pattern that was characteristic for the used senescence protocol. When we tested the lysophosphatidylcholines for senescence-associated secretory phenotype activity, we found that they elicit chemokine release in nonsenescent fibroblasts but also interfere with toll-like receptor 2 and 6/CD36 signaling and phagocytic capacity in macrophages. Using matrix-assisted laser desorption/ ionization Fourier transform ion cyclotron resonance mass spectrometry imaging, we localized two lysophosphatidylcholine species in aged skin. This suggests that lysophospholipids may facilitate immune evasion and low-grade chronic inflammation in skin aging.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA