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Sirtuins in dermatology: applications for future research and therapeutics

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Abstract

Sirtuins are a family of seven proteins in humans (SIRT1–SIRT7) that are involved in multiple cellular processes relevant to dermatology. The role of sirtuins in other organ systems is established. However, the importance of these proteins in dermatology is less defined. Recently, sirtuins gained international attention because of their role as “longevity proteins” that may extend and enhance human life. Sirtuins function in the cell via histone deacetylase and/or adenosine diphosphate ribosyltransferase enzymatic activity that target histone and non-histone substrates, including transcription regulators, tumor suppressors, structural proteins, DNA repair proteins, cell signaling proteins, transport proteins, and enzymes. Sirtuins are involved in cellular pathways related to skin structure and function, including aging, ultraviolet-induced photoaging, inflammation, epigenetics, cancer, and a variety of cellular functions including cell cycle, DNA repair and proliferation. This review highlights sirtuin-related cellular pathways, therapeutics and pharmacological targets in atopic dermatitis, bullous dermatoses, collagen vascular disorders, psoriasis, systemic lupus erythematosus, hypertrophic and keloid scars, cutaneous infections, and non-melanoma and melanoma skin cancer. Also discussed is the role of sirtuins in the following genodermatoses: ataxia telangiectasia, Cowden’s syndrome, dyskeratosis congenita, Rubenstein–Taybi, Werner syndrome, and xeroderma pigmentosum. The pathophysiology of these inherited diseases is not well understood, and sirtuin-related processes represent potential therapeutic targets for diseases lacking suitable alternative treatments. The goal of this review is to bring attention to the dermatology community, physicians, and scientists, the importance of sirtuins in dermatology and provide a foundation and impetus for future discussion, research and pharmacologic discovery.

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Abbreviations

ADPRT:

ADP-ribosyl transferase

BCC:

Basal cell carcinoma

CREB:

cAMP response binding protein

CS:

Cowden syndrome

DC:

Dyskeratosis congenita

DNA:

Deoxyribonucleic acid

Dnmt:

DNA methyltransferase

HAT:

Histone acetyl transferase

HDAC:

Histone deacetylase

HDACi:

Histone deacetylase inhibitor

HPV:

Human papilloma virus

H2O2 :

Hydrogen peroxide

mTOR:

Mammalian target of rapamycin

NAD+ :

Nicotinamide adenine dinucleotide

NAM:

Nicotinamide

NER:

Nucleotide excision repair

NF-κB:

Nuclear factor-kappa B

PTEN:

Phosphatase and tensin homolog

Rb:

Retinoblastoma

RTS:

Rubenstein–Taybi syndrome

SCC:

Squamous cell carcinoma

siRNA:

Small interfering ribonucleic acid

SLE:

Systemic lupus erythematosus

SIRT:

Silent information regulator homolog (sirtuin)

TNFα:

Tumor necrosis factor alpha

UV:

Ultraviolet (radiation)

WS:

Werner syndrome

XP:

Xeroderma pigmentosum

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Authors and Affiliations

  1. Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY, 11203, USA

    Melissa Serravallo, Jared Jagdeo, Sharon A. Glick, Daniel M. Siegel & Neil I. Brody

  2. Department of Dermatology, University of California at Davis, 3301 C Street, Sacramento, CA, 95816, USA

    Jared Jagdeo

  3. Dermatology Service, Sacramento VA Medical Center, Mather, CA, 95655, USA

    Jared Jagdeo

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  1. Melissa Serravallo
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  3. Sharon A. Glick
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Correspondence to Jared Jagdeo.

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M. Serravallo and J. Jagdeo contributed equally to the preparation of this manuscript.

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Serravallo, M., Jagdeo, J., Glick, S.A. et al. Sirtuins in dermatology: applications for future research and therapeutics. Arch Dermatol Res 305, 269–282 (2013). https://doi.org/10.1007/s00403-013-1320-2

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