医学考博题源报刊选读：Nipping ageing in the bud(4)

“Exercise has been shown to reduce senescent cells, though only after a gruelling, high-intensity session”

“运动已被证明可以减少衰老细胞，尽管只有在艰苦的高强度运动之后”

A related problem is that, even in people who have tipped over the threshold whereby senescent cells cause more harm than good, the cells still perform a vital function. “Some senescent cells are there because they’re important for tissue regeneration and wound healing” says Partridge. “You don’t want to kill those guys off. You want [to target] the guys who’ve been hanging around for ages who have had DNA damage.”

与此相关的一个问题是，即使人体内的衰老细胞已经超过了阈值，弊大于利，但这些细胞仍然发挥着重要的功能。帕特里奇说：“有些衰老细胞之所以存在，是因为它们对组织再生和伤口愈合非常重要。你不想杀了那些家伙。你想[瞄准]那些已经存在了很长时间、DNA已经受损的细胞。”

tip over 使翻倒

tip over the edge 情绪失控：指某人的情绪或行为变得无法控制，达到极端或危险的程度。

threshold n.门槛，阈值

tissue regeneration 组织再生

wound healing 伤口愈合

kill off 消灭

hang around 闲荡；徘徊

If senolytics inhibit normal wound healing, their use in humans could be “essentially doomed”, argues Sundeep Khosla, also at the Mayo Clinic in Rochester. Two studies found that administering senolytics to mice with skin or lung injuries inhibits wound healing, which doesn’t bode well, he says. But, paradoxically, three other studies show that senolytics enhance the healing of bone fractures.

同样在罗切斯特梅奥诊所工作的孙迪普·科斯拉（Sundeep Khosla）认为，如果抗衰老药物会抑制正常的伤口愈合，那么它们在人类身上的应用“基本注定要失败”。他说，有两项研究发现，给皮肤或肺部受伤的小鼠服用抗衰老药会抑制伤口愈合，这可不是什么好兆头。但矛盾的是，另外三项研究显示，抗衰老药能促进骨折愈合。

doomed adj. 注定的；命定的

bode well 预示好兆头：表示某种迹象或情况预示着好的结果或成功的可能性。

bone fracture 骨折

There is a way to reconcile these findings. The skin and lung studies used continuous drug dosing to take out all the senescent cells, whereas the bone studies employed a regime called “hit-and-run” —the drugs are given intermittently rather than continuously, allowing some senescent cells to survive. This implies that there is a sweet spot for the number of senescent cells to obtain anti-ageing effects without disrupting wound healing, says Khosla. But more research is needed.

有一种方法可以协调这些研究结果。皮肤和肺部研究采用连续给药的方法来清除所有衰老细胞，而骨骼研究则采用一种称为“打了就跑”的方法——间歇性给药，而不是连续给药，从而让一些衰老细胞存活下来。科斯拉说，这意味着在衰老细胞的数量上存在一个最优值，可以在不破坏伤口愈合的情况下获得抗衰老效果。但还需要更多的研究。

reconcile v. 调和，使协调一致；（使）和解，（使）恢复友好关系；调停，调解（争吵）

hit-and-run adj. 打了就跑的

intermittently adv. 间歇地

sweet spot 最有效点；最佳击球位置

Hit-and-run has another benefit in that it reduces the risks of side effects, which are associated with several senolytics, says Kirkland. Dasatinib, for instance, can cause fluid on the lungs and suppression of bone marrow—but these only appear after several weeks of continuous use.

科克兰说，“即用即走”疗法的另一个好处是降低了副作用的风险，因为几种抗衰老药物都有副作用，如达沙替尼会导致肺部积水和骨髓抑制。但这些副作用只有在连续使用数周后才会出现。

suppression n.抑制

marrow n. 髓，骨髓；精华；活力

Another possible solution is to give upon culling senescent cells and to just tame them instead. Another class of drugs called senomorphics (also known as senostatics or senomodulators) is in the offing. These medications suppress the SASP rather than push senescent cells into self-destruction. The two most promising drugs, metformin and rapamycin, are already on the radar. The American Federation for Aging Research is currently preparing a series of six-year clinical trials to test whether metformin—a diabetes drug with proven anti-ageing properties in animals—can delay the onset of further age-related conditions in people who already have one. Its TAME (Targeting Aging with Metformin) trial is “the first large clinical trial in modern medicine to test if human ageing can be treated with a drug”, according to Hong Zhu at Campbell University in Buies Creek, North Carolina. Rapamycin, meanwhile, increases lifespan and health span in animals and is currently being tested as an anti-ageing drug in dogs.

另一种可能的解决方案是放弃剔除衰老细胞，转而控制它们。另一种被称为抗衰老剂（senomorphics）的药物（也称为senostatics或senomodulators）即将问世。这类药物能抑制 SASP，而不是促使衰老细胞自我毁灭。两种最有希望的药物——二甲双胍和雷帕霉素已受到关注。美国老龄化研究联合会（American Federation for Aging Research）目前正准备进行一系列为期六年的临床试验，以测试二甲双胍——一种在动物身上证实具有抗衰老特性的糖尿病药物——是否能延缓已经患有老年病的人进一步出现与衰老相关的病症。据北卡罗来纳州布伊斯克里克坎贝尔大学的朱虹（音译）介绍，TAME（二甲双胍抗衰老）试验是“现代医学中首个测试是否可以用药物治疗人类衰老的大型临床试验”。同时，雷帕霉素能延长动物的寿命和健康寿命，目前正在狗身上进行抗衰老药物试验。

give upon 放弃，停止努力，不再尝试或继续进行某事。

cull vt. 挑选, 剔除

tame v. 驯化，驯服；制服，控制；开垦，开辟

be in the offing 即将到来

medication n. 给药

promising adj. 有希望的, 有前途的

be on the radar 被注意到

onset n. 开始

There is a possible downside with senomorphics, however. They generally need continuous dosing rather than hit-and-run, which probably increases the risk of side effects, says Kirkland. Continuous high doses of rapamycin in mice, for example, are toxic to the kidneys and gonads and increase susceptibility to infections.

不过，senomorphics 也可能存在缺点。柯克兰说，它们通常需要持续给药，而不是随用随停，这可能会增加副作用的风险。例如，小鼠连续服用大剂量雷帕霉素会对肾脏和性腺产生毒性，并增加感染的可能性。

downside n. 缺点，不利方面

be toxic to… 对…有害

susceptibility(to…) n.易感性

While we wait on senolytic drugs, other options already exist. Exercise has been shown to reduce the burden of senescent cells in skeletal muscle and fat tissue, though a recent study found that the benefits only accrue from a gruelling session of high-intensity exercise. Caloric restriction is also a senolytic, says Kirkland Meanwhile, short bursts of ultrasound have been shown to reverse senescence in cultured human cells and to rejuvenate old mice through an as-yet unknown mechanism.

在我们等待抗衰老药物的同时，其他选择已经存在。运动已被证明可以减轻骨骼肌和脂肪组织中衰老细胞的负担，不过最近的一项研究发现，只有进行高强度的剧烈运动才能产生这种益处。柯克兰说，限制热量也能促进衰老。同时，短时间的超声波已被证明能逆转培养人体细胞的衰老，并通过一种尚不清楚的机制使老龄小鼠恢复青春。

reduce the burden 减轻负担

accrue from 来源于：指某事物的产生或获得是由于特定的原因或来源

reverse vt. & vi. (使)反转; (使)颠倒; (使)翻转

rejuvenate vt. 使变得年轻, 使恢复活力

as-yet 至今仍

An awful lot hinges on the success—or otherwise—of senolytics. One of the goals of the TAME trial, says lead investigator Nir Barzilai, director of the Institute for Aging Research at Albert Einstein College of Medicine in New York City, is to persuade the FDA to recognise ageing as a disease in its own right, which could change the landscape of the entire field. “The FDA will accept TAME results if they are positive,” he says. In doing so, it will open the door to treating ageing as something that can be “cured”. I am down on my creaky old knees hoping that happens.

衰老药物的成功与否关系重大。首席研究员、纽约阿尔伯特-爱因斯坦医学院衰老研究所所长尼尔·巴齐莱（Nir Barzilai）说，TAME试验的目标之一是说服美国食品药品管理局承认衰老本身是一种疾病，这可能会改变整个领域的格局。他说：“如果TAME的结果呈阳性，美国食品及药物管理局（FDA）就会接受。”这将为把衰老作为一种可以‘治愈’的疾病打开大门。我双膝跪地，希望这一切成真。

a lot hinges on… 很大程度上取决于……

open the door to doing 打开……的大门

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