Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Nov 22:14:1297637.
doi: 10.3389/fphys.2023.1297637. eCollection 2023.

The role of cellular senescence in skin aging and age-related skin pathologies

Toby Chin #  1 , Xin Er Lee #  2 , Pei Yi Ng  2 , Yaelim Lee  3 , Oliver Dreesen  2   3
Affiliations
Review

The role of cellular senescence in skin aging and age-related skin pathologies

Toby Chin et al. Front Physiol. .

Abstract

Aging is the result of a gradual functional decline at the cellular, and ultimately, organismal level, resulting in an increased risk of developing a variety of chronic illnesses, such as cardiovascular disease, stroke, cancer and diabetes. The skin is the largest organ of the human body, and the site where signs of aging are most visible. These signs include thin and dry skin, sagging, loss of elasticity, wrinkles, as well as aberrant pigmentation. The appearance of these features is accelerated by exposure to extrinsic factors such as ultraviolet (UV) radiation or pollution, as well as intrinsic factors including time, genetics, and hormonal changes. At the cellular level, aging is associated with impaired proteostasis and an accumulation of macromolecular damage, genomic instability, chromatin reorganization, telomere shortening, remodelling of the nuclear lamina, proliferation defects and premature senescence. Cellular senescence is a state of permanent growth arrest and a key hallmark of aging in many tissues. Due to their inability to proliferate, senescent cells no longer contribute to tissue repair or regeneration. Moreover, senescent cells impair tissue homeostasis, promote inflammation and extracellular matrix (ECM) degradation by secreting molecules collectively known as the "senescence-associated secretory phenotype" (SASP). Senescence can be triggered by a number of different stimuli such as telomere shortening, oncogene expression, or persistent activation of DNA damage checkpoints. As a result, these cells accumulate in aging tissues, including human skin. In this review, we focus on the role of cellular senescence during skin aging and the development of age-related skin pathologies, and discuss potential strategies to rejuvenate aged skin.

Keywords: SASP; aging; lamin B1; senescence; senolytics; skin; wounds.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic representation of skin aging. Intrinsic and extrinsic factors (e.g., chronological aging, pollution, UV exposure) result in the accumulation of senescent cells in aged skin. In the aged skin, physiological changes occur—such as thinning of epidermis, flattening of dermal-epidermal junction (DEJ), hyperpigmentation, loss of melanocytes and degradation of collagen and elastin as indicated—that result in the manifestation of various aging phenotypes. Created with BioRender.com.
FIGURE 2
FIGURE 2
Characteristics of young [22-year-old (22yo)] versus aged [57-year-old (57yo)] sun-protected human skin. Aged skin exhibits a flattened dermal-epidermal junction, decreased number of melanocytes (MelA) and reduced intensity for collagen 17a (Col17a) and collagen 7 (Col7).
FIGURE 3
FIGURE 3
Schematic representation depicting the positive and negative effects of senescent cells on wound healing. The transient accumulation of senescent cells can exert a positive effect on wound healing via the secretion of SASP factors. PDGF-AA induces fibroblast-myofibroblast differentiation and promotes wound contraction. Persistent accumulation of senescent cells can be detrimental to wound healing via the secretion of SASP factors such as MMPs and ILs which degrade the ECM and induce inflammation, as well as the paracrine induction of senescence in neighbouring non-senescent cells. Created with BioRender.com.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abercrombie M., Dunn G. (1975). Adhesions of fibroblasts to substratum during contact inhibition observed by interference reflection microscopy. Exp. Cell Res. 92 (1), 57–62. 10.1016/0014-4827(75)90636-9 - DOI - PubMed
    1. Acosta J. C., Banito A., Wuestefeld T., Georgilis A., Janich P., Morton J. P., et al. (2013). A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat. Cell Biol. 15 (8), 978–990. 10.1038/ncb2784 - DOI - PMC - PubMed
    1. Adamus J., Aho S., Meldrum H., Bosko C., Lee J.-M. (2014). p16INK4A influences the aging phenotype in the living skin equivalent. J. Invest. Dermatol 134 (4), 1131–1133. 10.1038/jid.2013.468 - DOI - PMC - PubMed
    1. Akbar A. N., Henson S. M. (2011). Are senescence and exhaustion intertwined or unrelated processes that compromise immunity? Nat. Rev. Immunol. 11 (4), 289–295. 10.1038/nri2959 - DOI - PubMed
    1. Andrade A. M., Sun M., Gasek N. S., Hargis G. R., Sharafieh R., Xu M. (2022). Role of senescent cells in cutaneous wound healing. Biology 11 (12), 1731. 10.3390/biology11121731 - DOI - PMC - PubMed

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by funds from the Agency for Science, Technology and Research (A∗STAR), Singapore and the A∗STAR Skin Research Labs to OD.