“…An age‐related decline in tissue regeneration and function could be attributed to an impaired stem cell function, a theory known as “stem cell aging” (López‐Otín, Blasco, Partridge, Serrano, & Kroemer, 2013); however, it remains elusive what are the crucial drivers for aging at cellular and molecular levels. An aged epidermis shows histological and functional changes, including a decreased proliferative capacity (Charruyer et al, 2009; Gilchrest, 1983) and lower success in epidermal engraftment (Piccin & Morshead, 2010), a decrease in epidermal thickness, flattening of epidermal–dermal junction (Changarathil, Ramirez, Isoda, Sada, & Yanagisawa, 2019; Giangreco, Goldie, Failla, Saintigny, & Watt, 2010; Langton, Halai, Griffiths, Sherratt, & Watson, 2016; Makrantonaki & Zouboulis, 2007), delayed wound healing (Keyes et al, 2016), decreased barrier function (Gonzales & Fuchs, 2017), increased risk of cancer (Adams, Jasper, & Rudolph, 2015; López‐Otín et al, 2013), impaired HF stem cell lineages (Matsumura et al, 2016), and interaction with their niche (Ge et al, 2020). Mutant mouse studies and transcriptome analyses have suggested that the age‐related epidermal dysfunction could be due to defects in IFE and HF stem cells to interact with other cell types or extracellular matrix in skin (Ge et al, 2020; Giangreco, Qin, Pintar, & Watt, 2008; Keyes et al, 2016; Liu et al, 2019; Matsumura et al, 2016; Watanabe et al, 2017).…”