GENETIC analyses of human skin are revealing more about what makes us look old. As well as throwing up ways to smooth away wrinkles, the studies may provide a quantifiable way to test claims made for skin products.
In the past, cosmetics companies relied on subjective assessments of skin appearance, and changes in its thickness, colour and protein composition, to evaluate the effectiveness of their products and work out the quantities of ingredients needed to get the best results. "It was totally hit and miss," says Rosemary Osborne of Procter and Gamble in Cincinnati, Ohio.
Now skin researchers, including those at P&G, are starting to use DNA microarrays, common in the drugs industry, to measure the expression of thousands of genes in skin of different ages. "It's a way of finding mechanisms that were not known before," says Fernand Labrie, who studies skin genomics at Laval University in Quebec City, Canada.
P&G recently compared gene expression in skin samples from the buttocks and forearms of 10 young and 10 older women. In older skin, they found a decrease in the expression of genes involved in cholesterol and fatty acid synthesis. More surprisingly, the opposite was true for genes associated with inflammation and other components of the immune system, suggesting that the immune system may play a role in ageing.
Treating the older skin with niacinamide, which helps skin retain moisture, damped down expression of genes related to inflammation. "We believe that improving the barrier results in a 'resignalling' of key molecular components of the skin," says Jay Tiesman of P&G. Targeting this inflammation might one day help to keep wrinkles at bay. The findings will appear in the Journal of Drugs in Dermatology in July.
Identifying a "genetic signature" of younger skin should also provide a benchmark for testing existing skin products. For example, P&G is measuring the effects on gene expression of a skin cream ingredient called pal-KT. Previous approaches suggested it increased production of structural skin proteins like collagen and laminin. Gene analysis indicates it also affects the expression of genes involved in wound healing.
P&G isn't alone, cosmetics firm L'Oréal claims to have identified differences in the way genes in old and young skin respond to physical damage: changes in gene expression began just 6 hours after damage in young skin but took around 30 hours to kick in with older skin. What's more, around 25 genes differ in their response to skin damage in young and old skin, says L'Oréal.
Rigorous studies in people are needed to confirm that changing gene expression in older skin to match younger skin improves skin quality. "You could find that a molecule is up or down-regulated, but whether that relates to a consumer noticing a difference is a big jump," says Diona Damian at the University of Sydney, Australia.
If new tools become available for assessing skin products, this could force cosmetics companies to back up claims about their products with hard evidence.
"If you really want to bring cosmetics into the field of rigorous scientific evidence, genomics may be the best and most quantitative way of doing it," says Labrie.
究竟是什么让我们看起来衰老,通过对于人类肌肤的基因分析,更多奥秘正在浮出水面。这些研究提出了很多平复皱纹的方法,也提供了几种可以用来测试化妆品公司所声称的护肤品功效的办法。
过去,化妆品公司都是依靠对肌肤整体外观的主观评定,以及肌肤厚度、肤色和蛋白质组成的变化情况,来衡量其产品的效力,以确定要达到最佳效果所需的各种配方。"完全就是一点一点试出来的。"来自俄亥俄州辛辛那提宝洁公司的罗斯玛丽。奥斯本说。
目前,很多皮肤研究员,包括宝洁公司的皮肤研究员,已经开始使用制药业中常用的DNA微序列来分析不同年龄肌肤中上千基因的表达式。"用这种办法可以发现一些以往未可知的机理。"在加拿大魁北克市拉瓦尔大学研究肌肤基因组学的费尔南多。莱柏瑞说。
宝洁最近在一项研究中取10位年轻女性和10位年长女性的臀部和前臂肌肤样本,比对其基因表达。研究发现,年长者的肌肤中胆固醇和脂肪酸合成物的基因表达有所衰减。然而更令人惊讶的是,与免疫系统中炎症和其他成分相关的基因却正好相反-表达有所增长,这说明免疫系统在衰老的过程中起了很重要的作用。
用有助于保湿的烟酰胺来处理衰老肌肤,可以使与炎症相关基因的表达式有所衰减。"我们相信通过阻碍其增长,可以使肌肤的关键分子组成'重新发出信号'."宝洁公司的杰伊。缇斯曼说。针对炎症细胞的各种措施,很有可能能够有效地牵制皱纹的生长。这些发现结果将会刊登在7月的Journal of Drugs in Dermatology .
对于年轻肌肤"基因签章"的识别,同样也会为现有的各种护肤品提供测试基准。例如,宝洁正在测量润肤霜中一种叫做"pal-KT"的成分对于基因表达所起的效用。之前的研究结果显示它可以增加胶原蛋白、层粘连蛋白等肌肤结构蛋白的生成。基因分析表明它对与伤口愈合相关基因的表达也有一定作用。
宝洁并非唯一在做此类研究的公司,欧莱雅声称已发现年老和年轻肌肤中,基因对于物理性损坏的反应有所不同:年轻肌肤损伤6小时后,基因表达即有变化,而年老肌肤则需要30小时左右。更有甚者,二者相比,约25种基因的反应有差异,欧莱雅说。
改变年老肌肤的基因表达式,使其与年轻肌肤相同,可以有助于改善肌肤质量-要证实这一点还需要做很多缜密的研究。"你可能会发现某种分子被人为控制增长或衰减,但它引起的差异是否能被消费者注意到,这是一个飞跃。"澳洲悉尼大学的戴奥娜。达米安说。
如果这种评定护肤品的新办法研制成功,化妆品公司将会被强制要求提供确凿证据来证明其声称的产品功效。
"如果你确实想找到能证明化妆品功效的严谨的科学依据,那么基因组学是最佳的量化分析的办法。"莱柏瑞说。