Seidman M D, Khan M J, Bai U, Shirwany N, Quirk W S
Department of Otolaryngology Head & Neck Surgery, Henry Ford Health System, Detroit, Michigan 48323, USA.
Am J Otol. 2000 Mar;21(2):161-7. doi: 10.1016/s0196-0709(00)80003-4.
Compounds that upregulate mitochondrial function in an aging model will improve hearing and reduce some of the effects of aging.
Reactive oxygen metabolites (ROM) are known products of oxidative metabolism and are continuously generated in vivo. More than 100 human clinical conditions have been associated with ROM, including atherosclerosis, arthritis, autoimmune diseases, cancers, heart disease, cerebrovascular accidents, and aging. The ROM are extremely reactive and cause extensive DNA, cellular, and tissue damage. Specific deletions within the mitochondrial DNA (mtDNA) occur with increasing frequency in age and presbyacusis. These deletions are the result of chronic exposure to ROM. When enough mtDNA damage accrues, the cell becomes bioenergetically deficient. This mechanism is the basis of the mitochondrial clock theory of aging, also known as the membrane hypothesis of aging. Nutritional compounds have been identified that enhance mitochondrial function and reverse several age-related processes. It is the purpose of this article to describe the effects of two mitochondrial metabolites, alpha-lipoic acid and acetyl L-carnitine, on the preservation of age-related hearing loss.
Twenty-one Fischer rats, aged 24 months, were divided into three groups: acetyl-l-carnitine, alpha-lipoic acid, and control. The subjects were orally supplemented with either a placebo or one of the two nutritional compounds for 6 weeks. Auditory brainstem response testing was used to obtain baseline and posttreatment hearing thresholds. Cochlear, brain, and skeletal muscle tissues were obtained to assess for mtDNA mutations.
The control group demonstrated an expected age-associated threshold deterioration of 3 to 7 dB in the 6-week study. The treated subjects experienced a delay in progression of hearing loss. Acetyl-l-carnitine improved auditory thresholds during the same time period (p<0.05). The mtDNA deletions associated with aging and presbyacusis were reduced in the treated groups in comparison with controls.
These results indicate that in the proposed decline in mitochondrial function with age, senescence may be delayed by treatment with mitochondrial metabolites. Acetyl-l-carnitine and alpha-lipoic acid reduce age-associated deterioration in auditory sensitivity and improve cochlear function. This effect appears to be related to the mitochondrial metabolite ability to protect and repair age-induced cochlear mtDNA damage, thereby upregulating mitochondrial function and improving energy-producing capabilities.
在衰老模型中上调线粒体功能的化合物将改善听力并减轻一些衰老效应。
活性氧代谢产物（ROM）是氧化代谢的已知产物，在体内持续产生。超过100种人类临床病症与ROM有关，包括动脉粥样硬化、关节炎、自身免疫性疾病、癌症、心脏病、脑血管意外和衰老。ROM具有极强的反应性，会导致广泛的DNA、细胞和组织损伤。线粒体DNA（mtDNA）中的特定缺失在衰老和老年性聋中出现的频率越来越高。这些缺失是长期暴露于ROM的结果。当积累了足够的mtDNA损伤时，细胞在生物能量方面就会出现缺陷。这种机制是衰老的线粒体时钟理论的基础，也被称为衰老的膜假说。已鉴定出能增强线粒体功能并逆转一些与年龄相关过程的营养化合物。本文的目的是描述两种线粒体代谢产物α-硫辛酸和乙酰左旋肉碱对预防年龄相关性听力损失的作用。
将21只24个月大的Fischer大鼠分为三组：乙酰左旋肉碱组、α-硫辛酸组和对照组。给实验对象口服安慰剂或两种营养化合物之一，持续6周。使用听性脑干反应测试来获取基线和治疗后的听力阈值。获取耳蜗、脑和骨骼肌组织以评估mtDNA突变情况。
在为期6周的研究中，对照组出现了预期的与年龄相关的阈值恶化，恶化程度为3至7分贝。接受治疗的实验对象听力损失进展出现延迟。乙酰左旋肉碱在同一时期改善了听觉阈值（p<0.05）。与对照组相比，治疗组中与衰老和老年性聋相关的mtDNA缺失减少。
这些结果表明，在所提出的随着年龄增长线粒体功能下降的情况下，用线粒体代谢产物进行治疗可能会延缓衰老。乙酰左旋肉碱和α-硫辛酸可减少与年龄相关的听觉敏感性恶化并改善耳蜗功能。这种作用似乎与线粒体代谢产物保护和修复年龄诱导的耳蜗mtDNA损伤的能力有关，从而上调线粒体功能并提高能量产生能力。
