Clinical consequences of age-related skin barrier dysfunction. Part II. Approach to barrier dysfunction in the geriatric population.

Aging is associated with significant changes to skin structure and function which lead to distinct clinical needs in geriatric dermatology patients. By understanding the relationship between altered skin function with aging and the clinical implications for geriatric dermatology patients, dermatologists can guide patients in developing a preventive regimen and managing age-related skin pathology. The second article of this 2-part continuing medical education series reviews the most common conditions affecting geriatric dermatology patients and specific treatment considerations with a focus on the impact of age-related skin barrier dysfunction.

Clinical consequences of age-related skin barrier dysfunction. Part I. Structural, molecular and physiologic changes with cutaneous aging.

Aging is associated with significant changes to skin structure and function. As the United States population ages, dermatologists are increasingly presented with the clinical consequences of these changes. Understanding the biology of aging skin allows dermatologists to best guide patients towards proactive treatment of age-related skin disease. The first article of this 2-part continuing medical education series reviews the structural, molecular and functional changes associated with skin aging.

Adipocytes Provide Fatty Acids to Acute Lymphoblastic Leukemia Cells.

BACKGROUND: There is increasing evidence that adipocytes play an active role in the cancer microenvironment. We have previously reported that adipocytes interact with acute lymphoblastic leukemia (ALL) cells, contributing to chemotherapy resistance and treatment failure. In the present study, we investigated whether part of this resistance is due to adipocyte provision of lipids to ALL cells. METHODS: We cultured 3T3-L1 adipocytes, and tested whether ALL cells or ALL-released cytokines induced FFA release. We investigated whether ALL cells took up these FFA, and using fluorescent tagged BODIPY-FFA and lipidomics, evaluated which lipid moieties were being transferred from adipocytes to ALL. We evaluated the effects of adipocyte-derived lipids on ALL cell metabolism using a Seahorse XF analyzer and expression of enzymes important for lipid metabolism, and tested whether these lipids could protect ALL cells from chemotherapy. Finally, we evaluated a panel of lipid synthesis and metabolism inhibitors to determine which were affected by the presence of adipocytes. RESULTS: Adipocytes release free fatty acids (FFA) when in the presence of ALL cells. These FFA are taken up by the ALL cells and incorporated into triglycerides and phospholipids. Some of these lipids are stored in lipid droplets, which can be utilized in states of fuel deprivation. Adipocytes preferentially release monounsaturated FFA, and this can be attenuated by inhibiting the desaturating enzyme steroyl-CoA decarboxylase-1 (SCD1). Adipocyte-derived FFA can relieve ALL cell endogenous lipogenesis and reverse the cytotoxicity of pharmacological acetyl-CoA carboxylase (ACC) inhibition. Further, adipocytes alter ALL cell metabolism, shifting them from glucose to FFA oxidation. Interestingly, the unsaturated fatty acid, oleic acid, protects ALL cells from modest concentrations of chemotherapy, such as those that might be present in the ALL microenvironment. In addition, targeting lipid synthesis and metabolism can potentially reverse adipocyte protection of ALL cells. CONCLUSION: These findings uncover a previously unidentified interaction between ALL cells and adipocytes, leading to transfer of FFA for use as a metabolic fuel and macromolecule building block. This interaction may contribute to ALL resistance to chemotherapy, and could potentially be targeted to improve ALL treatment outcome.