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Page 2 of 10     Abadías-Granado et al. Plast Aesthet Res 2021;8:27  https://dx.doi.org/10.20517/2347-9264.2020.199

                                                         [3]
               The skin, the largest organ of the human body , is in direct and continuous contact with the external
                                                                                     [4]
               environment, and, consequently, it is exposed to the microorganisms that inhabit it . In addition, these skin
               commensal microbial communities interact with each other, as well as with the host cells and the immune
                     [3]
               system . In this sense, it is clear that the immunological system of the host modulates the composition of
               these communities, and, conversely, the microbes present on the skin have a great impact on human
               immune system .
                            [3,5]
               Different factors influence the diversity in the composition of this ecosystem. In fact, the anatomy and
               physiology of the skin determine the skin bacterial diversity, such as the axillae, forehead, palms, fingers, or
               feet . Even on a particular niche of the body, the skin microbiota is still complicated by a combination of
                  [2]
               both external and internal factors, including, but not limited to, gender, age, environmental conditions such
               as pollution and the climate, genetics, hormones, cosmetics, diet, immune response, and lifestyles in
               general .
                     [5-8]

               In this regard, different distributions of microorganism species have been identified in sebaceous, moist, or
               dry locations [6,8,9] . In addition, areas more exposed to the outside environment may contain a greater
               proportion of “transitory” microorganisms, compared to less exposed ones .
                                                                              [6,9]

               The perception of the skin as an ecosystem can help us to understand the delicate balance between host and
                                                                                              [4]
               microorganisms and how the alteration of any of them can result in skin diseases or infections .
               The objective of this article is to review the existing evidence in relation to the microbiome and aging,
               especially that of the skin, and the possibility of manipulating the microbiome to prevent and treat age-
               related comorbidities and premature skin aging.


               This is a narrative review of the subject. We obtained the articles by searching in PubMed. The search terms
               were microbiome, aging, skin, and skin cancer. To identify the articles relevant to the purposes of the review,
               we read abstracts, results, and, when necessary, the full texts to ascertain which ones contain pertinent
               information.


               THE TECHNIQUES FOR SKIN MICROBIAL ANALYSIS
               There are two main sampling methods for collecting resident skin microbiota. On the one hand, skin
               swabbing using a sterile cotton swab is a simple, quick, and non-invasive method for large-scale skin
               sampling. However, this method can accurately collect only resident microbiota from the stratum corneum;
               therefore, it does not provide a full spectrum picture of the skin microbiota, particularly in some specific
               subniches, such as the dermis. On the other hand, punch biopsies are invasive but offer the best
               representation of skin microbiota in deep epidermis, dermis, and glands such as the sebaceous gland.
               Nevertheless, due to its invasive nature, the latter is rarely used for qualitative analyses .
                                                                                       [10]
               Regarding the technique, it must be sterile to ensure that bacterial DNA sequences are not introduced into
               the sample from sampling equipment, lab reagents, clinicians, etc. . Additionally, cold storage at -20 or
                                                                         [11]
               -80 ℃ or in liquid nitrogen is a standard practice to limit further microbial growth and long-term DNA
               degradation .
                         [10]

               Once the samples are obtained and properly stored, there are several methods to extract DNA, including the
               REPLI-g Midi kit (Qiagen, Limberg, The Netherlands), Qiagen DNA Extraction Kit (Qiagen), and DNeasy
               DNA Extraction kit (Qiagen) . These techniques recognize the specific DNA or RNA (16S ribosomal
                                         [11]
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