译者注：也许，你不在乎活多久。也许，你没有耐心看这种翻译文章。（因为是基于机器翻译的。）那么，你就记住：“牙龈疾病与心脏病的风险增加有关，也可能与痴呆症有关。”好好保护你的牙齿。不要认为老人掉牙是“正常的”。另外，注意“健康饮食、戒掉糖、每天锻炼、和优先睡眠”。

雷帕霉素或可延缓衰老。

以下是测试该药物的方法之一

几年前，Matt Kaeberlein 被诊断出患有肩周炎。“情况非常糟糕，”他回忆道。他睡不好觉，因为疼痛无法投球。他的医生建议他进行康复治疗，并告诉他可能需要一年时间才能好转。

他感到沮丧，决定尝试雷帕霉素。近年来，一些知名的长寿科学家开始服用这种药物，希望能够抵御与年龄相关的健康问题。到目前为止，它还没有在服用它来抗衰老的人身上进行过测试，但雷帕霉素已被证明可以延长小鼠的寿命。

“我决定试一试，”Kaeberlein 说。这是他“首次涉足生物黑客领域”，他对接下来发生的事情非常满意。“两周内，50% 的疼痛消失了，”他说。10 周后，他的（肩膀）活动范围恢复正常，疼痛也完全消失了。

“而且疼痛再也没有复发，”他说。

Kaeberlein 对雷帕霉素并不陌生。他是一名生物学家，与他人共同创立了“狗衰老项目”，研究雷帕霉素如何影响狗的健康寿命。他还是华盛顿大学健康衰老与长寿研究所的前主任。

雷帕霉素于 20 世纪 90 年代末首次获得 FDA准用于（器官）移植患者。高剂量时，它会抑制免疫系统。Kaeberlein 说，低剂量时，它似乎有助于抑制炎症。它通过抑制体内一种名为 mTOR 的信号通路起作用——这似乎是寿命和衰老的关键调节器。

虽然雷帕霉素并未获批用于止痛或抗衰老，但一些医生开具非说明书所列的雷帕霉素处方，目的是预防与年龄相关的疾病。Kaeberlein 和他的同事调查了大约 300 名服用低剂量雷帕霉素的患者，许多人报告了药物的益处。

但轶事不能代替科学。要弄清药物的风险和益处，需要进行研究。这就需要牙医。

华盛顿大学的 Jonathan An 博士已获得 FDA 批准，在牙龈疾病患者中测试雷帕霉素——这是一种常见疾病，往往会随着年龄的增长而加速。当他治疗牙龈疾病患者时，他说除了清洁和去除牙菌斑（细菌堆积）外，他能做的不多。“我们所做的就是包扎伤口，”他说。他的目标是找到并治疗疾病的根本原因。

已经有一些（器官）移植患者的证据表明雷帕霉素可能有助于改善口腔健康。作为研究的一部分，An 博士和他的同事还将测量参与者的微生物组和生物钟的变化。

这项研究将招募 50 岁以上患有牙龈疾病的参与者。他们将间歇性地服用不同剂量的药物，持续 8 周。然后，An 博士将能够确定该药物是否安全有效。

他说，如果雷帕霉素具有有益作用，它将有助于证明有可能针对疾病的根本原因。“这实际上归结为针对衰老的生物学，”他说。

An 博士认为牙龈疾病可能是与年龄相关的疾病的煤矿中的金丝雀。例如，牙龈疾病与心脏病的风险增加有关，也可能与痴呆症有关。科学家说，与牙周病有关的口腔细菌可能会引起炎症，这可能会导致血管“级联”损伤，从而导致心脏或大脑出现问题。

“如果我们能够针对潜在的生物学，我们预测它可能会解决许多其他潜在疾病，” An 博士说。

雷帕霉素是一种仿制药，因此制药公司几乎没有动力资助新的研究。An 博士和他的合作者已经获得了进行试验的资助，这可能为进一步的研究打开大门，以确定雷帕霉素是否有助于预防或减缓其他与年龄相关的疾病。

巴克衰老负责人埃里克·维尔丁 (Eric Verdin) 医生表示，他的团队正在为雷帕霉素的更多研究筹集资金。他说，还有很多未解问题，例如“单剂量不同浓度的效果是什么？”他想在服用雷帕霉素的人身上寻找“分子特征”。他想了解更多关于剂量和间隔的信息，因为许多医生在开具非说明书处方时建议循环服用和停用该药物。

研究人员也在研究其他可能以类似方式起作用的药物，并且正在推动新药的开发——或其他针对生物衰老的干预措施。有一项新的 1 亿美元 XPRIZE Healthspan 竞赛，旨在加速 Hevolution 和其他资助者支持的该领域的研究。

目前，XPRIZE 创始人 Peter Diamandis 是一名撰写长寿文章的医生，他说他服用雷帕霉素。“我每周日晚上服用六毫克，也就是每周一次，”持续三个月，他解释说。然后他停药一个月。“我相信雷帕霉素——以我使用它的方式——是安全的，并且好处多于坏处，”他说。

戴曼迪斯不断用许多健康指标监测自己的身体状况，他承认，考虑到他为保持健康所做的所有其他事情，包括健康饮食、戒掉糖、每天锻炼、和优先睡眠，很难确定雷帕霉素的效果。

他的计划是继续保持健康的生活习惯，同时支持对干预措施和策略的研究，以帮助人们延长健康寿命。

Rapamycin may slow aging. Here's one way the drug will be tested

JULY 1, 20245:00 AM ET

HEARD ON  MORNING EDITION

Allison Aubrey

https://www.npr.org/sections/shots-health-news/2024/07/01/nx-s1-5008777/rapamycin-aging-disease-drug-humans-research

A few years back, Matt Kaeberlein was diagnosed with a frozen shoulder. “It was really bad,” he recalls. He wasn’t sleeping well and couldn’t throw a ball due to the pain. His doctor recommended physical therapy, and told him that it may take a year to get better.

Feeling frustrated, he decided to try rapamycin. In recent years, some high-profile longevity scientists have started taking the drug in hopes of fending off age-related health problems. So far, it’s untested in people taking it for anti-aging, but rapamycin has been shown to extend the lifespan of mice.

“I decided to try it,” Kaeberlein says. It was his "first foray into biohacking,” and he was very pleased with what happened next. “Within two weeks, 50% of the pain was gone,” he says. And by the end of 10 weeks, he had regained range of motion and the pain was completely gone.

“And it hasn’t come back,” he says.

Kaeberlein is no stranger to rapamycin. He’s a biologist and co-founded the Dog Aging Project to study how rapamycin influences dogs’ healthspans. He’s also the former director of the Healthy Aging and Longevity Research Institute at the University of Washington.

Rapamycin was first approved by the FDA for use in transplant patients in the late 1990s. At high doses it suppresses the immune system. At low doses, Kaeberlein says it seems to help tamp down inflammation. It works by inhibiting a signaling pathway in the body called mTOR — which seems to be a key regulator of lifespan and aging.

The drug is not approved for pain or anti-aging, but some physicians prescribe rapamycin off-label with the aim of fending off age-related conditions. Kaeberlein and his colleagues surveyed about 300 of these patients, who take low doses, and many report benefits.

But anecdotes are no replacement for science. To figure out the risks and benefits of a drug, research is needed. And that's where a dentist comes in.

Dr. Jonathan An, at the University of Washington, has been granted FDA approval to test rapamycin in patients with gum disease — a common condition that tends to accelerate with age. When he treats patients with gum disease, he says there’s not much he can do beyond cleaning and removing the plaque — a buildup of bacteria. “All we’re doing is putting a bandage on,” he says. His goal is to find and treat the underlying cause of the disease.

There’s already some evidence from transplant patients that rapamycin may help improve oral health. And as part of the study, An and his collaborators will also measure changes in participants’ microbiomes and their biological clocks.

The study will enroll participants over the age of 50 who have gum disease. They will take the drug, at various doses, intermittently for 8 weeks. Then, An will be able to determine if the drug is safe and effective.

If rapamycin has a beneficial effect he says, it will help demonstrate that it’s possible to target the root cause of the disease. “It really comes down to targeting the biology of aging,” he says.

Dr. An thinks gum disease may be a kind of canary in the coalmine of age-related diseases. For instance, gum disease is linked to a higher risk of heart disease, and maybe dementia, too. Scientists say it’s possible that bacteria in the mouth linked to periodontal disease causes inflammation, which may cause a “cascade” of damage to blood vessels, leading to problems in the heart or brain.

“If we can target that underlying biology, we predict that it might address a lot of these other underlying conditions,” An says.

Rapamycin is a generic drug, so pharmaceutical companies have little incentive to fund new research. An and his collaborators have received a grant to conduct the trial, which could open the door to further studies to determine whether rapamycin can help prevent or slow down other age-related diseases.

Eric Verdin, a physician who heads the Buck Institute for Research on Aging, says his group is fundraising for more research on rapamycin. He says there are a lot of unanswered questions, for example “what is the effect of different concentrations in a single dose?” And he wants to look for a “molecular signature” in people taking rapamycin. He wants to know more about doses and intervals, since many doctors prescribing it off-label recommend cycling on and off the drug.

Researchers are also working on other drugs that may work in similar ways, and there’s a push for new drugs — or other interventions that target biological aging. There’s a new $100 millionXPRIZE Healthspan competition, aimed at accelerating the research in the field supported by Hevolution and other funders.

For now, XPRIZE founder Peter Diamandis, a physician who writes about longevity, says he takes rapamycin. “I do six milligrams every Sunday night, so once a week," for three months, he explains. Then he takes a month off. "I believe that rapamycin — in the way I'm utilizing it — is safe and has more upside potential than downside,” he says.

Diamandis constantly monitors his body with many health metrics, and he acknowledges it’s hard to determine the effect of rapamycin given all the other things he does to stay healthy, including eating well, eliminating sugar, working out every day and prioritizing sleep.

His plan is to continue with healthy lifestyle habits while supporting research into interventions and strategies that can help people add more healthy years to their life.