A New Anti-Aging Drug Looks to Turn Back the Clock on Skin Age
A New Anti-Aging Drug Looks to Turn Back the Clock on Skin Age
A wave of biotech companies is looking to prove that it’s possible to slow down the aging process. Mountain View, California–based Rubedo Life Sciences is starting with the most outwardly visible sign: the skin.
一批生物技术公司正试图证明减缓衰老过程是可能的。总部位于加利福尼亚州山景城的 Rubedo Life Sciences 公司正从最直观的迹象入手：皮肤。
The company’s experimental treatment is showing early promise that it may be able to reduce the appearance of aging, according to data the company presented at the Aging Research and Drug Discovery meeting in Boston earlier this month.
根据该公司本月初在波士顿举行的“衰老研究与药物发现”会议上公布的数据，其试验性疗法已显示出初步前景，可能能够减少衰老迹象。
In a small clinical trial, Rubedo tested its topical cream on 11 people with atopic dermatitis, an inflammatory skin condition and the most common type of eczema. The drug targets a mechanism of cellular senescence, a biological state in which damaged or stressed cells permanently stop dividing but do not die. These senescent or “zombie” cells accumulate as people age and can release substances that contribute to inflammation and tissue damage, which contributes to disease.
在一项小型临床试验中，Rubedo 对 11 名患有特应性皮炎（一种炎症性皮肤病，也是最常见的湿疹类型）的患者测试了其外用乳膏。该药物针对的是细胞衰老机制，这是一种受损或受压细胞永久停止分裂但并未死亡的生物状态。随着年龄增长，这些衰老或“僵尸”细胞会不断积累，并释放出导致炎症和组织损伤的物质，从而引发疾病。
After four weeks of using the cream, participants lowered the biological age of their skin by about two years, on average. That estimate was based on an aging “clock” designed by a different company, Mitra Bio, which performed an independent analysis on participants’ skin samples. One person in the trial had a reduction of more than 11 years in skin age. Separately, Rubedo found that its treatment was tied to a reduction in inflammation-related markers and a 10 percent increase in a type of collagen associated with skin elasticity and structure.
在使用该乳膏四周后，参与者的皮肤生物学年龄平均降低了约两年。这一评估基于另一家公司 Mitra Bio 设计的衰老“时钟”，该公司对参与者的皮肤样本进行了独立分析。试验中有一人的皮肤年龄降低了超过 11 岁。此外，Rubedo 还发现，其疗法与炎症相关标志物的减少以及一种与皮肤弹性和结构相关的胶原蛋白增加 10% 有关。
Biological or epigenetic age is an estimate of how well a person is aging compared to their calendar age. Aging clocks like Mitra’s attempt to calculate this number by looking at patterns of methylations, chemical modifications to DNA that regulate how genes function and can change over time. That metric doesn’t necessarily prove that the body or a particular organ or tissue has become functionally younger, though.
生物学年龄或表观遗传年龄是对一个人相对于其实际年龄衰老程度的评估。像 Mitra 这样的衰老时钟试图通过观察甲基化模式（即调节基因功能并随时间变化的 DNA 化学修饰）来计算这一数值。然而，这一指标并不一定能证明身体或特定的器官或组织在功能上变得更年轻了。
“Our idea is to find ways to change the trajectory of how we age,” says Marco Quarta, Rubedo’s cofounder and chief scientific officer. “Aging is complex. There are many mechanisms, but cellular senescence is one of them.”
“我们的想法是找到改变衰老轨迹的方法，”Rubedo 的联合创始人兼首席科学官 Marco Quarta 表示，“衰老很复杂。它有许多机制，而细胞衰老就是其中之一。”
Senescent cells are also involved in normal biological processes, such as wound healing and tumor suppression, but their accumulation over time is associated with many age-related conditions. Getting rid of them is one of the leading strategies that anti-aging and longevity companies are pursuing.
衰老细胞也参与正常的生物过程，如伤口愈合和肿瘤抑制，但它们随时间的积累与许多与年龄相关的疾病有关。清除这些细胞是抗衰老和长寿公司正在追求的主要策略之一。
Rubedo’s approach aims to clear out senescent cells by targeting a protein known as GPX4, a gatekeeper for cell survival. By transiently turning off GPX4, the drug is designed to make senescent cells more susceptible to ferroptosis, a regulated form of cell death, while reviving stressed, non-senescent cells nearby.
Rubedo 的方法旨在通过靶向一种名为 GPX4 的蛋白质（细胞生存的守门人）来清除衰老细胞。通过暂时关闭 GPX4，该药物旨在使衰老细胞更容易发生铁死亡（一种受调节的细胞死亡形式），同时激活附近受压但未衰老的细胞。
In a separate study, researchers looked at the drug’s effect on actinic keratosis, a skin condition caused by sun damage and produces rough, scaly skin patches and can sometimes progress to skin cancer. In a trial of 18 people, the cream led to a 46 percent reduction in total lesions after a month of use.
在另一项研究中，研究人员观察了该药物对光化性角化病的影响。这是一种由阳光损伤引起的皮肤病，会产生粗糙、鳞屑状的皮肤斑块，有时会发展为皮肤癌。在一项 18 人的试验中，使用该乳膏一个月后，病变总数减少了 46%。
Rubedo is studying the same drug for psoriasis and skin with sun damage. Soon, the company will add androgenetic alopecia, a type of hereditary hair loss, to the list. CEO Frederick Beddingfield, previously the chief medical officer at Allergan, where he launched Botox, sees potential in a lower-potency, over-the-counter version for general skin aging, which would compete with retinol. The company is also formulating the drug into a pill to study whether it can be used to treat metabolic conditions associated with aging.
Rubedo 正在研究同一种药物对银屑病和晒伤皮肤的疗效。不久，该公司还将把雄激素性脱发（一种遗传性脱发）纳入研究范围。首席执行官 Frederick Beddingfield 曾任艾尔建（Allergan）的首席医疗官，并在那里推出了保妥适（Botox）。他认为，一种低效力的非处方版本在普通皮肤抗衰老领域具有潜力，可以与视黄醇竞争。该公司还在将该药物制成药丸，以研究其是否可用于治疗与衰老相关的代谢疾病。
“It’s great to see them doing this work,” says Eric Verdin, president and CEO of the Buck Institute for Research on Aging, which has developed several aging clocks. “I would probably be a little circumspect about what these clocks really measure, because right now, there are a proliferation of them.”
“很高兴看到他们开展这项工作，”巴克衰老研究所（Buck Institute for Research on Aging）总裁兼首席执行官 Eric Verdin 表示，该研究所已经开发了几种衰老时钟，“对于这些时钟到底测量了什么，我可能会持谨慎态度，因为目前这类时钟层出不穷。”
Plus, the results that patients will care about is how their skin actually looks and feels, not a result from a biological aging test.
此外，患者真正关心的是皮肤的实际外观和触感，而不是生物衰老测试的结果。
And senescence is just one piece of the aging puzzle, says Anthony Rossi, a dermatologist at Memorial Sloan Kettering Cancer Center. “Some senescent cells are good because they turn things off, like cancer progression.”
纪念斯隆凯特琳癌症中心（Memorial Sloan Kettering Cancer Center）的皮肤科医生 Anthony Rossi 表示，衰老只是衰老难题的一部分。“一些衰老细胞是有益的，因为它们能抑制某些过程，比如癌症的发展。”
He says the science is novel but the work is still very early-stage, and it will be interesting to see how it affects biological aging in people with healthy skin, not just those with certain skin conditions. “The best anti-aging routine right now is sleep, a good diet, and exercise,” he says. For now, at least.
他认为这项科学研究很新颖，但仍处于非常早期的阶段。观察它如何影响皮肤健康人群（而不仅仅是患有特定皮肤病的人群）的生物衰老过程将会很有趣。“目前最好的抗衰老方法是睡眠、良好的饮食和锻炼，”他说。至少目前是这样。