Seidman M D, Bai U, Khan M J, Quirk W S
Department of Otolaryngology-Head and Neck Surgery, Henry Ford Hospital, West Bloomfield, MI 48323, USA.
Arch Otolaryngol Head Neck Surg. 1997 Oct;123(10):1039-45. doi: 10.1001/archotol.1997.01900100009001.
The membrane hypothesis of aging proposes an association between reactive oxygen metabolites and aging processes. Reactive oxygen metabolites are a normal by-product of oxidative phosphorylation and are also formed under conditions of ischemia, hypoperfusion, and as a result of environmental contaminants. Among the many detrimental activities of reactive oxygen metabolites, also known as free oxygen radicals, is direct damage to mitochondrial DNA. Progressive accumulation of mitochondrial DNA damage renders cells unable to conduct oxidative phosphorylation reactions effectively, thereby leading to a bioenergetically deficient cell. Over time, mitochondrial DNA damage accumulates and leads to cellular dysfunction with subsequent organ failure, aging, and ultimately, death. This sequence forms the basis of the membrane hypothesis of aging.
To determine if the membrane hypothesis of aging may be involved in the development of presbyacusis.
Fischer rats from 4 age groups were tested for auditory sensitivity using the auditory brainstem response. Brain, stria vascularis, and auditory nerve tissues were harvested and mitochondrial DNA was amplified to identify the highly conserved cytochrome b and ND1-16S ribosomal RNA segment of the NADH genes, as well as a 4834-base pair (bp) deletion associated with aging.
Fischer rats (n=28) from 4 age groups were used: young (2-4 months [n=9]), mid-young (9-11 months [n=5]), mid-old (18-20 months [n=5]), and old (30-34 months [n=9]).
The results demonstrate a progressive reduction in auditory sensitivity with age. The mitochondrial DNA studies identify a significant increase in the presence of the 4834-bp deletion in the aged subjects compared with the young.
These findings raise the possibility that the 4834-bp deletion may be associated with presbyacusis, as well as with aging.
衰老的膜假说提出活性氧代谢产物与衰老过程之间存在关联。活性氧代谢产物是氧化磷酸化的正常副产物，也在缺血、灌注不足以及环境污染物作用的条件下形成。在活性氧代谢产物（也称为游离氧自由基）的众多有害活动中，对线粒体DNA的直接损伤是其中之一。线粒体DNA损伤的逐渐积累使细胞无法有效地进行氧化磷酸化反应，从而导致细胞能量代谢不足。随着时间的推移，线粒体DNA损伤不断积累，导致细胞功能障碍，随后引发器官衰竭、衰老，最终导致死亡。这一系列过程构成了衰老的膜假说的基础。
确定衰老的膜假说是否可能与老年性聋的发生有关。
对来自4个年龄组的Fischer大鼠进行听觉脑干反应测试，以检测其听觉敏感性。采集大脑、血管纹和听神经组织，扩增线粒体DNA，以鉴定NADH基因高度保守的细胞色素b和ND1 - 16S核糖体RNA片段，以及与衰老相关的4834个碱基对（bp）的缺失。
使用来自4个年龄组的Fischer大鼠（n = 28）：年轻组（2 - 4个月[n = 9]）、青年中期组（9 - 11个月[n = 5]）、老年中期组（18 - 20个月[n = 5]）和老年组（30 - 34个月[n = 9]）。
结果表明，听觉敏感性随年龄增长而逐渐降低。线粒体DNA研究发现，与年轻组相比，老年组中4834 - bp缺失的发生率显著增加。
这些发现提示4834 - bp缺失可能与老年性聋以及衰老有关。
