热量限制减少炎症,防止细胞衰老的负面影响

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Caloric Restriction Reduces Inflammation, Prevents Negative Effects of Aging in Cells

By 作者 NutritionReview.org -March 4, 2020 2020年3月4日01760

If you want to reduce inflammation throughout your body, delay the onset of age-related diseases, and live longer, you have to eat less food. That’s the conclusion of a new study by scientists from the US and China that provides the most detailed report to date of the cellular effects of a calorie-restricted diet. While the benefits of caloric restriction have long been known, the new results show how this restriction can protect against aging in cellular pathways, as detailed in Cell on February 27, 2020.

如果你想减少全身的炎症,延缓与年龄有关的疾病的发作,延长寿命,你就必须少吃东西。这是美国和中国科学家的一项新研究得出的结论,该研究提供了迄今为止关于限制热量饮食的细胞效应的最详细报告。虽然限制热量摄入的好处早已为人所知,但新的研究结果表明,这种限制可以通过细胞途径防止衰老,详见2020年2月27日的《细胞》杂志。

Aging is the highest risk factor for many human diseases, including cancer, dementia, diabetes and metabolic syndrome. Caloric restriction has been shown in animal models to be one of the most effective interventions against these age-related diseases. And although researchers know that individual cells undergo many changes as an organism ages, they have not known how caloric restriction might influence these changes. According to  Juan Belmonte of the Salk Institute,

衰老是许多人类疾病的最高危险因素,包括癌症、痴呆、糖尿病和代谢症候群。热量限制在动物模型中已被证明是对这些年龄相关疾病最有效的干预措施之一。尽管研究人员知道,随着机体年龄的增长,单个细胞会发生许多变化,但他们还不知道限制热量摄入会如何影响这些变化。据索尔克研究所的胡安 · 贝尔蒙特称,

“We already knew that calorie restriction increases life span, but now we’ve shown all the changes that occur at a single-cell level to cause that.” “我们已经知道卡路里限制可以延长寿命,但现在我们已经展示了单细胞水平的所有变化都会导致这种结果。”

In the new paper, Belmonte and his collaborators – including three alumni of his Salk lab who are now professors running their own research programs in China – compared rats who ate 30 percent fewer calories with rats on normal diets. The animals’ diets were controlled from age 18 months through 27 months. (In humans, this would be roughly equivalent to someone following a calorie-restricted diet from age 50 through 70.)

在这篇新论文中,贝尔蒙特和他的合作者——包括他的索尔克实验室的三名校友,他们现在都是在中国运行自己研究项目的教授——比正常饮食的老鼠少摄入30% 的卡路里。这些动物的饮食从18个月到27个月都受到控制。(对于人类来说,这大致相当于一个人从50岁到70岁期间遵循限制热量饮食。)

At both the start and the conclusion of the diet, Belmonte’s team isolated and analyzed a total of 168,703 cells from 40 cell types in the 56 rats. The cells came from fat tissues, liver, kidney, aorta, skin, bone marrow, brain and muscle. In each isolated cell, the researchers used single-cell genetic-sequencing technology to measure the activity levels of genes. They also looked at the overall composition of cell types within any given tissue. Then, they compared old and young mice on each diet.

在饮食的开始和结束阶段,贝尔蒙特的研究小组从56只老鼠的40种细胞中分离并分析了168,703个细胞。这些细胞来自脂肪组织、肝脏、肾脏、主动脉、皮肤、骨髓、大脑和肌肉。在每个分离的细胞中,研究人员使用单细胞基因测序技术来测量基因的活性水平。他们还观察了任何特定组织中细胞类型的总体构成。然后,他们比较了每种饮食中的老年和年轻老鼠。

Many of the changes that occurred as rats on the normal diet grew older didn’t occur in rats on a restricted diet.

正常饮食的老鼠变老时发生的许多变化,在限制饮食的老鼠身上并没有发生。

Even in old age, many of the tissues and cells of animals on the diet closely resembled those of young rats. 即使在老年时期,饮食喂养的动物的许多组织和细胞与幼鼠的组织和细胞非常相似

Overall, 57 percent of the age-related changes in cell composition seen in the tissues of rats on a normal diet were not present in the rats on the calorie restricted diet.

总的来说,正常饮食组织中与年龄相关的细胞组成变化中有57% 在限制热量饮食组中没有出现。

“This approach not only told us the effect of calorie restriction on these cell types, but also provided the most complete and detailed study of what happens at a single-cell level during aging,” says co-corresponding author Guang-Hui Liu, a professor at the Chinese Academy of Sciences.

“这个方法不仅告诉了我们卡路里限制对这些细胞类型的影响,而且还提供了在衰老过程中单细胞水平发生的最完整和详细的研究,”中国科学院教授,共同通讯作者刘说。

Some of the cells and genes most affected by the diet related to immunity, inflammation and lipid metabolism. The number of immune cells in nearly every tissue studied dramatically increased as control rats aged but was not affected by age in rats with restricted calories. In brown adipose tissue – one type of fat tissue – a calorie-restricted diet reverted the expression levels of many anti-inflammatory genes to those seen in young animals.

一些受饮食影响最大的细胞和基因与免疫、炎症和脂质代谢有关。随着对照组大鼠年龄的增长,几乎所有组织中的免疫细胞数量都显著增加,但是限制热量组大鼠的免疫细胞数量没有受到年龄的影响。在褐色脂肪组织—- 一种脂肪组织—- 限制热量摄入的饮食中,许多抗炎基因的表达水平逆转到那些在幼小动物身上看到的表达水平。

“The primary discovery in the current study is that the increase in the inflammatory response during aging could be systematically repressed by caloric restriction.” “当前研究的主要发现是,在老化过程中炎症反应的增加可以被系统地抑制热量限制。”

When the researchers homed in on transcription factors – essentially master switches that can broadly alter the activity of many other genes – that were altered by caloric restriction, one stood out. Levels of the transcription factor Ybx1 were altered by the diet in 23 different cell types. The scientists believe Ybx1 may be an age-related transcription factor and are planning more research into its effects.

当研究人员把注意力集中在转录因子上时,一个突出的例子就出现了。转录因子本质上是主开关,可以广泛地改变许多其他基因的活性。在23种不同类型的细胞中,转录因子的 Ybx1水平被饮食所改变。科学家们认为 Ybx1可能是一种与年龄有关的转录因子,并计划对其影响进行更多的研究。

“People say that ‘you are what you eat,’ and we’re finding that to be true in lots of ways,” says Concepcion Rodriguez Esteban, another of the paper’s authors and a staff researcher at Salk. “The state of your cells as you age clearly depends on your interactions with your environment, which includes what and how much you eat.”

“人们说‘吃什么就是什么’ ,我们发现这在很多方面都是正确的,”康塞普西翁•罗德里格斯•埃斯特班(Concepcion Rodriguez Esteban)说,他是该论文的另一位作者,也是 Salk 的一名研究员。“随着年龄的增长,细胞的状态显然取决于你与环境的互动,包括你吃什么和吃多少。”

The team is now trying to utilize this information in an effort to discover aging drug targets and implement strategies towards increasing life and health span.

研究小组现在正试图利用这一信息来努力发现老化药物靶标,并实施增加寿命和健康寿命的策略。

Source: Caloric Restriction Reprograms the Single-Cell Transcriptional Landscape of Rattus Norvegicus Aging. Cell, 2020; DOI: 10.1016/j.cell.2020.02.008

资料来源: 卡路里限制重组褐鼠衰老的单细胞转录景观. Cell,2020; DOI: 10.1016/j.Cell. 2020.02.008

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