CD38和 NAD 在衰老中的作用研究


Investigating CD38 and NAD in Aging

Of late, there has been a growing interest in exploring mechanisms related to nicotinamide adenine dinucleotide (NAD) and the way in which their operation changes over the course of aging. This research has grown out of the last decade of attempts to produce calorie restriction mimetic drugs that might modestly slow aging, lengthy efforts that have resulted in a better understanding of some aspects of metabolism, but few leads to drug candidates. NAD is important in mitochondrial function, and many methods of slowing aging in laboratory species – calorie restriction included – involve changes in this part of cellular biochemistry. Increased levels of NAD in mice appear to produce better mitochondrial function and greater cellular housekeeping efforts, the second of which is fairly common among interventions that influence mitochondrial biochemistry. The flux of reactive oxygen species produced by mitochondria in the course of generating energy store molecules for the cell is used as one of many intracellular signals, and produces the housekeeping reaction when it grows larger.

最近,人们对探索与烟酰胺腺嘌呤二核苷酸有关的机制以及它们在衰老过程中运作变化的方式越来越感兴趣。这项研究是在过去十年的尝试基础上发展起来的,这些尝试都是为了制造一些类似卡路里限制的药物,这些药物可以适度地延缓衰老,这些漫长的努力已经导致了对新陈代谢某些方面的更好的理解,但是很少有药物候选者。NAD 在线粒体功能中起着重要作用,许多实验室物种延缓衰老的方法,包括卡路里限制,都涉及到细胞生物化学这一部分的变化。小鼠中 NAD 水平的增加似乎产生了更好的线粒体功能和更大的细胞内务管理努力,其次是相当普遍的干预措施,影响线粒体生物化学。线粒体在为细胞产生能量储存分子的过程中产生的活性氧类通量被用作许多细胞内信号之一,当它变大时产生内务处理反应。

Researchers have identified the enzyme, called CD38, that is responsible for the decrease in nicotinamide adenine dinucleotide (NAD) during aging, a process that is associated with age-related metabolic decline. Results demonstrated an increase in the presence of CD38 with aging in both mice and humans. “Previous studies have shown that levels of NAD decline during the aging process in several organisms. This decrease in NAD appears to be, at least in part, responsible for age-related metabolic decline.” Researchers have shown that CD38, an enzyme that is present in inflammatory cells, is directly involved in the process that mediates the age-related NAD decline. Comparing 3- to 32-month-old mice, researchers found that levels of CD38 increased at least two to three times during chronological aging in all tissues tested, including the liver, fat, spleen and skeletal muscle.

研究人员已经确定了一种叫做 CD38的酶,它负责在衰老过程中减少烟酰胺腺嘌呤二核苷酸,这个过程与年龄相关的代谢下降有关。结果表明,随着年龄的增长,小鼠和人类中 CD38的存在都有所增加。“以前的研究表明,在一些生物体的衰老过程中,NAD 的水平会下降。NAD 的这种下降似乎至少在一定程度上导致了年龄相关的代谢下降。”研究人员表明,CD38,一种存在于炎症细胞中的酶,直接参与介导与年龄相关的 NAD 下降的过程。研究人员发现,比较3个月到32个月大的小鼠,在实验所有组织(包括肝脏、脂肪、脾脏和骨骼肌)的时间老化过程中,CD38水平至少增加了2到3倍。

To determine if the increase in CD38 observed in mice was also present in humans, researchers compared the levels in groups of individuals who were approximately 34-years-old to groups of individuals who were approximately 61-years-old. Similar to their observations in mice, researchers found that CD38 increased up to two-and-a-half times in the fat tissue of older individuals. “The future of our research will be to develop compounds that can inhibit the function of CD38 to increase NAD levels during aging. We are also investigating the mechanisms that lead to the increase in CD38 during the aging process.”

为了确定在小鼠中观察到的 CD38的增加是否也存在于人类中,研究人员将大约34岁的人群与大约61岁的人群进行了比较。与他们在老鼠身上的观察结果相似,研究人员发现,在老年人的脂肪组织中,CD38增加了2.5倍。“我们研究的未来将是开发能够抑制 CD38功能的化合物,在衰老过程中增加 NAD 水平。我们也在研究老化过程中导致 CD38增加的机制。”


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