Skin aging: are adipocytes the next target?

Kruglikov, Ilja L.; Scherer, Philipp E.

doi:10.18632/aging.100999

Cited by 61 publications

(61 citation statements)

References 110 publications

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“…Recent work highlighted the importance of adipocytes in maintaining skin homeostasis, contributing to the regulation of hair cycle, wound healing, and immune function Rivera-Gonzalez et al, 2014). We assessed the age-related oscillations of dWAT in 2-, 6-, 11-, and 13month-old mice (Foster et al, 2018;Kruglikov and Scherer, 2016;Wang et al, 2013a). Consistent with previous reports in B6D2 females (Wang et al, 2013b), CO dWAT thickness increased at 6-and 11-months relative to 2-month and was significantly reduced at 13-month relative to 11-month ( Figure 4a).…”

Section: Middle-aged Mr Epidermal Knockout Skin Features Compartment-mentioning

confidence: 99%

Epidermal Mineralocorticoid Receptor Inactivation Affects the Homeostasis of All Skin Layers in Chronologically Aged Mice

Bigas

Sevilla

Pérez

2020

Journal of Investigative Dermatology

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The increased production of endogenous glucocorticoids (GCs) in the skin of the elderly population contributes to age-related defects strikingly similar to those occurring after pharmacologic treatments with GCs. GCs act through the ligand-dependent transcription factors GC receptor (GR) and mineralocorticoid receptor (MR). We reported that epidermal MR plays nonredundant roles relative to GR in adult mouse skin homeostasis; however, its relative contribution to natural skin aging has not been previously investigated. A 13-month-old MR epidermal knockout (MR EKO ) mice showed differential features of aging relative to controls (CO) in all skin compartments. MR EKO mice were resistant to age-induced epidermal atrophy but showed reduced dermal thickness, with decreased collagen deposition and decreased SMAD2 and 3 activity. Importantly, the dermal white adipose tissue (dWAT) was 2.5-fold enlarged in 13-month MR EKO versus CO, featuring adipocyte hyperplasia and hypertrophy at least in part through early increases in Pparg. These changes correlated with compartment-specific alterations in GC signaling. In addition, conditioned medium from MR EKO keratinocytes increased adipocyte differentiation, indicating paracrine regulation of adipogenesis through mechanisms that include activation of b-catenin signaling. These findings highlight the importance of epidermal MR in regulating cross-talk among skin compartments in naturally aged skin through GC and bcatenin signaling pathways.

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Section: Middle-aged Mr Epidermal Knockout Skin Features Compartment-mentioning

confidence: 99%

Epidermal Mineralocorticoid Receptor Inactivation Affects the Homeostasis of All Skin Layers in Chronologically Aged Mice

Bigas

Sevilla

Pérez

2020

Journal of Investigative Dermatology

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“…In addition, soluble cytokines are produced in the upper epidermis upon UV exposure and diffuse into the sWAT, causing loss of PPARγ expression, as well as reduced free fatty acid and triglyceride content. In mice, chronic exposure to UVA causes transition of dermal adipocytes to myofibroblasts, leading to replacement of dWAT with fibrotic tissue and thereby promoting morphological and functional alterations in the skin [53]. Taken together, these processes induce loss of sWAT and concurrent accumulation of vWAT in the skin with age, promoting the typical appearance of aged skin.…”

Section: Impact Of Age-induced Macromolecular Damage On (Pre-)adipocymentioning

confidence: 99%

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Schosserer

Grillari²,

Wolfrum

et al. 2017

Gerontology

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Aging is a time-related process of functional decline at organelle, cellular, tissue, and organismal level that ultimately limits life. Cellular senescence is a state of permanent growth arrest in response to stress and one of the major drivers of aging and age-related disorders. Senescent cells accumulate with age, and removal of these cells delays age-related disorders in different tissues and prolongs healthy lifespan. One of the most studied aging mechanisms is the accumulation of reactive oxygen species damage in cells, organs, and organisms over time. Elevated oxidative stress is also found in metabolic diseases such as obesity, metabolic syndrome and associated disorders. Moreover, dysregulation of the energy homeostasis is also associated with aging, and many age-related genes also control energy metabolism, with the adipose organ, comprising white, brite, and brown adipocytes, as an important metabolic player in the regulation of whole-body energy homeostasis. This review summarizes transformations in the adipose organ upon aging and cellular senescence and sheds light on the reallocation of fat mass between adipose depots, on the metabolism of white and brown adipose tissue, on the regenerative potential and adipogenic differentiation capacity of preadipocytes, and on alterations in mitochondria and bioenergetics. In conclusion, the aging process is a lifelong, creeping process with gradual decline in (pre-)adipocyte function over time. Thus, slowing down the accumulation of (pre-)adipocyte damage and dysfunction, removal of senescent preadipocytes as well as blocking deleterious compounds of the senescent secretome are protective measures to maintain a lasting state of health at old age.

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“…Following treatment with bleomycin, excessive skin scarring is accompanied by the loss of adipocytes and conversion of adipose progenitors into myofibroblasts 96 . In analogy with these observations, researchers have proposed that dWAT might contribute to skin fibrosis via the so-called adipocyte-to-myofibroblast transition mechanism during skin aging, including UV-induced aging 97 and male pattern baldness 98 .…”

Section: Defence Functions Of Dermal Fatmentioning

confidence: 97%

Emerging nonmetabolic functions of skin fat

Guerrero‐Juarez

Plikus

2018

Nat Rev Endocrinol

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Although the major white adipose depots evolved primarily to store energy, secrete hormones and thermo-insulate the body, multiple secondary depots developed additional specialized and unconventional functions. Unlike any other fat tissue, dermal white adipose tissue (dWAT) evolved a large repertoire of novel features that are central to skin physiology, which we discuss in this Review. dWAT exists in close proximity to hair follicles, the principal appendages of the skin that periodically grow new hairs. Responding to multiple hair-derived signals, dWAT becomes closely connected to cycling hair follicles and periodically cycles itself. At the onset of new hair growth, hair follicles secrete activators of adipogenesis, while at the end of hair growth, a reduction in the secretion of activators or potentially, an increase in the secretion of inhibitors of adipogenesis, results in fat lipolysis. Hair-driven cycles of dWAT remodelling are uncoupled from size changes in other adipose depots that are controlled instead by systemic metabolic demands. Rich in growth factors, dWAT reciprocally signals to hair follicles, altering the activation state of their stem cells and modulating the pace of hair regrowth. dWAT cells also facilitate skin repair following injury and infection. In response to wounding, adipose progenitors secrete repair-inducing activators, while bacteria-sensing adipocytes produce antimicrobial peptides, thus aiding innate immune responses in the skin.

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Skin aging: are adipocytes the next target?

Cited by 61 publications

References 110 publications

Epidermal Mineralocorticoid Receptor Inactivation Affects the Homeostasis of All Skin Layers in Chronologically Aged Mice

Epidermal Mineralocorticoid Receptor Inactivation Affects the Homeostasis of All Skin Layers in Chronologically Aged Mice

Age-Induced Changes in White, Brite, and Brown Adipose Depots: A Mini-Review

Emerging nonmetabolic functions of skin fat

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