How does cellular renewal influence skin aging?

Cellular renewal refers to the process by which skin cells continuously regenerate to maintain its integrity and protective function. This mechanism relies on the proliferation and differentiation of keratinocytes, the primary cells of the epidermis. These cells originate in the basal layer at the junction between the dermis and the epidermis, then progressively migrate toward the surface of the skin as they undergo a series of morphological and biochemical transformations. During their ascent, they lose their nuclei and become corneocytes, forming the stratum corneum, the outermost layer of the skin. This complete cycle, from basal keratinocyte to shed corneocyte, lasts on average 28 days in young adults.

With age, this renewal cycle gradually lengthens, resulting in an accumulation of dead surface cells and a duller complexion.

A study investigated the duration of cellular transit within the epidermis, meaning the time required for cells to move from one layer to the next: from the basal layer to the Malpighian layer, then to the granular layer, and finally to the cornified layer. The experiment involved volunteers aged 18 to 80 years. The results revealed that with advancing age, the epidermal cell migration time increased by approximately ten days compared to younger subjects, reflecting a significant slowdown in skin renewal. The values obtained for each age group are presented in the table below, with asterisks indicating statistically significant differences.

The aging of the skin is accompanied by a progressive weakening of the skin’s regenerative capabilities. This decline largely stems from the decreased efficacy of epidermal and follicular stem cells, which are responsible for the ongoing renewal of the epidermis. Although their numbers only moderately decline with age, their ability to divide and differentiate drops significantly, largely due to an altered microenvironment: the extracellular matrix loses cohesion, cell-to-cell communication becomes dysregulated, and inflammatory signals intensify. These disturbances reduce the stem cells’ capacity for regular renewal, resulting in skin that is less resilient and slower to heal.

At the molecular level, the slowdown of cellular renewal is exacerbated by the accumulation of senescent cells. These non-dividing cells secrete an array of pro-inflammatory mediators called SASP (Senescence-Associated Secretory Phenotype), which impair the function of neighboring cells. Concurrently, processes such as telomere shortening, oxidative stress, and the dysregulation of proliferation-related genes, such as p53, HES1, KLF6 or COL17A1, contribute to the slowdown of cellular renewal. These internal changes create a vicious cycle in which skin renewal becomes progressively slower, while its structural integrity deteriorates.

Extrinsic factors, such as UV rays and pollution, amplify these intrinsic effects of aging. They cause damage to stem cell DNA, disrupt their microenvironment, and accelerate their functional exhaustion. The skin thus ages visibly, with the appearance of wrinkles, a dulling of the complexion, and a loss of elasticity, and functionally, with a weakened skin barrier and reduced repair capacity.

The slowdown in cellular turnover is not only a manifestation of aging: it is also one of its primary driving forces.

To compensate for the natural slowdown in cellular turnover, exfoliation remains one of the most effective approaches today. By removing dead skin cells from the surface, mechanical scrubs or chemical exfoliants stimulate keratinocyte proliferation and promote renewal of the stratum corneum. However, caution is warranted: while exfoliation is important in a skincare routine, it should only be performed once or twice a week to avoid weakening the skin.

Meanwhile, research is currently exploring new avenues to reactivate the biological mechanisms of cellular renewal. Among these, exosomes—tiny extracellular vesicles released by cells—are generating increasing interest. These structures play a role in intercellular communication and, according to some studies in vitro, could stimulate keratinocyte proliferation and support skin regeneration. Nonetheless, these observations remain, for now, confined to laboratory models, and their in vivo effectiveness on human skin has yet to be demonstrated. Further scientific work is therefore still required.

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• DELLAMBRA E. & al. Epigenetic regulation of skin cells in natural aging and premature aging diseases. Cells (2018).

• NIEMANN C. & al. Human skin stem cells and the ageing process. Experimental Gerontology (2018).

• LIU N. & al. Stem cell competition orchestrates skin homeostasis and ageing. Nature (2019).

• TSCHACHLER E. & al. Cell aging and cellular senescence in skin aging – Recent advances in fibroblast and keratinocyte biology. Experimental Gerontology (2020).

• LIU G.-H. & al. A single-cell transcriptomic atlas of human skin aging. Developmental Cell (2021).

• KIM M. & al. Structural and functional changes and possible molecular mechanisms in aged skin. International Journal of Molecular Sciences (2021).

• YANAGISAWA H. & al. Matricellular proteins in the homeostasis, regeneration, and aging of skin. International Journal of Molecular Sciences (2023).