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Can Skin Aging Contribute to Systemic Inflammaging?

  • Suzanne M. Pilkington
    Correspondence
    Corresponding author
    Affiliations
    Centre for Dermatology Research, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom

    Manchester Institute for Collaborative Research on Ageing, The University of Manchester, Manchester, United Kingdom
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  • Silvia Bulfone-Paus
    Affiliations
    Centre for Dermatology Research, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom

    The Lydia Becker Institute of Immunology and Inflammation, The University of Manchester, Manchester, United Kingdom
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  • Christopher E.M. Griffiths
    Affiliations
    Centre for Dermatology Research, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom

    Manchester Institute for Collaborative Research on Ageing, The University of Manchester, Manchester, United Kingdom

    NIHR Manchester Biomedical Research Centre, The University of Manchester, Manchester, United Kingdom
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  • Rachel E.B. Watson
    Affiliations
    Centre for Dermatology Research, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom

    Manchester Institute for Collaborative Research on Ageing, The University of Manchester, Manchester, United Kingdom

    NIHR Manchester Biomedical Research Centre, The University of Manchester, Manchester, United Kingdom
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Published:October 27, 2021DOI:https://doi.org/10.1016/j.jid.2021.09.032
      We read with interest the commentary by
      • Elias P.M.
      Barrier function in aging: comments on Pilkington et al. “Inflammaging and the Skin” [e-pub ahead of print].
      , which highlighted the role of impaired skin barrier function, in addition to senescence, in contributing to a sustained cytokine response that may have systemic consequences. Healthy-looking skin is often considered an indicator of good general health. This premise is based on the concept that systemic factors associated with poor health can influence the function and appearance of skin. Similarly, the increased inflammation associated with intrinsic aging could be a contributing factor to the decline in skin health observed in the elderly. However, it is also worth considering the reverse argument, whereby poor skin health may be the driver of an adverse systemic effect. Although it has been proposed that epidermal abnormalities in psoriasis and atopic dermatitis might drive systemic inflammation (
      • Elias P.M.
      • Steinhoff M.
      "Outside-to-inside" (and now back to "outside") pathogenic mechanisms in atopic dermatitis.
      ), it is difficult to rule out the contribution of circulating immune cells in these T-cell‒mediated diseases. In addition, the severity of barrier disruption could be important because
      • He H.
      • Del Duca E.
      • Diaz A.
      • Kim H.J.
      • Gay-Mimbrera J.
      • Zhang N.
      • et al.
      Mild atopic dermatitis lacks systemic inflammation and shows reduced nonlesional skin abnormalities.
      showed that mild atopic dermatitis was associated with skin-localized T helper type 2/T helper type 22 activation in the absence of systemic inflammation. Interestingly, it is documented that skin injury, including sunburn (
      • Shreedhar V.
      • Giese T.
      • Sung V.W.
      • Ullrich S.E.
      A cytokine cascade including prostaglandin E2, IL-4, and IL-10 is responsible for UV-induced systemic immune suppression.
      ) and thermal burns (
      • Duke J.M.
      • Randall S.M.
      • Boyd J.H.
      • Fear M.W.
      • Rea S.
      • Wood F.M.
      A retrospective cohort study to compare post-injury admissions for infectious diseases in burn patients, non-burn trauma patients and uninjured people.
      ;
      • Valvis S.M.
      • Waithman J.
      • Wood F.M.
      • Fear M.W.
      • Fear V.S.
      The immune response to skin trauma is dependent on the etiology of injury in a mouse model of burn and excision.
      ), can result in increased production of cytokines and systemic immune dysfunction. However, untangling the cause and effect in the context of human skin aging is a difficult task.
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