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When Exceptional Longevity Inspires Cosmetic Ingredients Industry EXPERTS’ OPINION OSMETOLOGY Healthy aging When exceptional longevity inspires cosmetic ingredients industry Figure 1. Getto leaves, Okinawa Island. The plant A. zerumbet (Pers.) B.L. Burtt & o i R.M. Sm, syn. Alpinia speciosa . B D I © The latest global report issued by the World OUR EXPERT with caloric restriction, which involves Health Organization (1) highlights the impor - reducing calorie intake without causing tance of promoting “Healthy Aging” and malnutrition or deficiencies (6) . In this Aïna QUEIROZ proposes a public health framework with Innovation & Scientific Com. Manager, context, the Okinawa generations born the initial key measures along these lines (2) . SEQENS before the Second World War and their “hara hachi bu ” philosophy, consisting in From this perspective, the study of cente - eating until 80% satiety, represents one of narians living in regions with higher than the best human examples of a naturally average life expectancy such as Okinawa calorie restricted population. In terms of Island constitute a valuable research mate - mechanisms, one consensus currently rial to understand healthy aging. As an Healthy aging and nutritional factors favours the hypothesis according to which illustration, the Okinawa Centenarian Beyond the intuitive influence of nutrition this low nutrient intake induces a hormesis Study (OCS) conducted on more than 900 on longevity, the US study conducted in or low level stress phenomenon, which centenarians since 1975, suggested that 1990-2010 has confirmed the major role of involves positive regulation of the biolo - genes, lifestyle and psychosocial factors dietary factors in the risk of early death gical pathways for resistance to other forms are key to explain this phenomenon (3) . and in reducing healthy life expectancy of stress (FOXO3, mTOR) (7) . (DALY) (4) . Conversely, the mortality rate Inspired by these unique characteristics, due to coronary heart disease and cancer Alongside this phenomenon, caloric res - Seqens Cosmetics went to Okinawa to meet is 80% and 40% lower, respectively, among triction mimetics (CRM) liable to stimulate local pharmacopoeia experts as well as the the elderly population in Okinawa, com - autophagy were also identified in the “Oki - principal OCS investigators in order to take pared with the American population (5) .The nawa Diet” (8) . This diet is thus thought to a closer look at the nutritional and psycho - “Traditional Okinawa Diet” is often men - represent a rich source of CRM, with spe - social factors contributing to this excep - tioned in order to explain the healthy lon - cific herbs and condiments, which are the tional longevity. gevity of the Okinawa population, together foundations of traditional medicine. Owing SPECIAL INTERNATIONAL ISSUE OF INDUSTRIES COSMÉTIQUES • APRIL 2019 - APRIL 2020 PAGE 55 EXPERTS’ OPINION OSMETOLOGY to its local popularity and the significant data on life expectancy in certain animal models (9) , the plant known locally in Japan as getto (Figure 1) is still receiving particu - larly close attention, as its consumption is thought to contribute to longevity (10) . Healthy aging and psychosocial factors In addition to their dietary habits, cente - narians stay active by walking or gardening daily and remain physically independent until a very advanced age in comparison with certain Western populations (11) . Accor - ding to tradition, they don’t eat on raised tables and chairs, but rather by sitting on tatami mats on the floor: sitting down and standing up several times during the day is therefore a vital part of daily physical exercise among the elderly, which improves physical balance and prevents the risk of falls which often result in detrimental bone fractures. The results of a large-scale popu - lation study in Japan, conducted by the Japan Public Health Centre (JPHC), esta - blish a clear correlation between daily phy - sical exercise in Japan and a significant reduction in the risk of all-cause mortality among both genders (12) . Figure 2. Ultrastructural appearance of dermal fibroblasts in healthy sunprotected hip skin from young and old individuals (18) . A and B: The cell from the section of young skin (A) is flattened and well spread, in contact Although harder to quantify, longevity in with collagen fibers over a high percentage of its surface. The cell in the old skin sample (B) is round and is in Okinawa is also facilitated by the existence contact with collagen over a smaller portion of its surface. C: Modelization of fibroblast interaction, Young versus Old. D: Quantification of contact between cells and collagen fibers. Values represent the percentage of the cell of genuine reassuring social networks, boundary in contact with collagen fibers ± SEM (P=0.01; two-tailed Student’s t-test). notably with the local tradition of moai , or social support groups. This preserves a very ancient tradition which developed among ning cutaneous connections could improve dermis. These tissue changes notably the farming communities in Okinawa, and its appearance, similar to how emotional cause slackening and the gradual deve - which promoted sharing and daily support, connections promote good general health. lopment of wrinkles. notably in the context of mutual arrange - ments for performing manual tasks (13) . By studying the consequences of aging at At cellular level, changes in the quality of tissue and cellular level, the research fibroblast anchorage to the extracellular The existence of this social support offers teams thus endeavoured to identify bio - matrix increase the open spaces surroun - members essential emotional security; logical pathways liable to promote “heal - ding the cells and reduce the amount of research thus suggests that real connections thy skin aging”. contact between these cells and collagen and social trust through traditional local fibers (16) with a negative impact on traction events help preserve good mental health (14) . Healthy skin aging forces and dermal cohesion. This decreased From the age of 50, dermal quality starts mechanical tension on fibroblasts reduces Aware of the important role of these social to deteriorate with a decrease of dermis the production of matrix constituents and connections in longevity and “healthy thickness and undulations of the dermo- stimulates the synthesis of enzymes which aging” in this geographical area, Seqens epidermal junction (DEJ). Age-related cause deterioration of the matrix (17) . Cell- aimed to study whether parallels could be deterioration of the papillary region dis - cell interaction is also affected by the aging drawn at skin level. In other words, this rupts the organisation and structure of process, with consequences on fibroblast involved determining whether strengthe - the matrix (15) , also affecting the reticular productivity: an aged cell isolated from its PAGE 56 SPECIAL INTERNATIONAL ISSUE OF INDUSTRIES COSMÉTIQUES • APRIL 2019 - APRIL 2020 EXPERTS’ OPINION OSMETOLOGY Untreated explants Treatment with 2% of getto extract +39%** Figure 3. Ex vivo results: Skin explants treatment with getto leaves extract at 2% versus untreated explants. After treatment of skin explant: Dermal-epidermal junction (DEJ) morphology and undulation are enhanced. The immunostaining (green) highlighted a significant enhancement of 39% (p<0.01) of laminin 5. D0 D28 Figure 4. Clinical Results. After 28 and 56 days of use, formulation with 2% of getto leaves extract on the top 20 responders improves skin texture and complexion (skin rosy versus yellowish aspect). fibroblast cluster, for instance, synthesizes red to cells obtained from young skin sec - played an age-dependent secretion pattern; less type I procollagen than a young fibro - tions (Figure 2) (18) . these are known as “skin aging-associated blast exposed to the same conditions (18) . secreted proteins” (SAASPs) (19) . Two-dimensional skin sections also show In addition to the reduction in the number that fibroblasts obtained from elderly popu - of fibroblasts during the aging process, The identification of substances liable to lations have a smaller surface area in their secretory profile also changes. Among boost extracellular matrix synthesis and contact with intact collagen fibrils compa - the 998 secreted proteins identified, 77 dis - organisation, fibroblast interaction with SPECIAL INTERNATIONAL ISSUE OF INDUSTRIES COSMÉTIQUES • APRIL 2019 - APRIL 2020 PAGE 57 EXPERTS’ OPINION OSMETOLOGY the surrounding environment, together zation, and in cell-matrix interactions, such Conclusion with cohesion between the dermis and epi - as collagens, elastin, biglycan, dermato - Experts in exceptional longevity suggested dermis through dermo-epidermal junction pontin, tenascin C, or integrin alpha-11. that aging is not limited to genetic consi - thus represents an interesting strategy for Effects on the inhibition of the expression derations, but also involves aspects such preserving healthy skin and improving its of genes involved in the deterioration of as nutritional and biopsychosocial factors. general appearance. the extracellular matrix, inflammation, or Seqens Cosmetics thus studied the proper - in the response to oxidative stress were ties of getto extract, known to contribute to From inspiration to active ingredient also observed. the particularly high life expectancy in Oki - The research strategy for developing a nawa. These studies therefore showed that natural healthy aging ingredient at Seqens At ex vivo scale, after treating skin explants this plant, in addition to its nutritional
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