Mitochondrial mutations in mammalian aging: an over-hasty about-turn?

نویسنده

  • Aubrey D N J de Grey
چکیده

The very low abundance of mitochondrial DNA (mtDNA) mutations in nearly all mammalian tissues even in old age has led most mitochondriologists to reject the idea that such mutations might have a causal role in aging, despite (1) the strong circumstantial (e. g., interspecies) evidence that they do have such a role, (2) the promulgation since 1998 of two detailed mechanisms whereby low levels of mtDNA mutations could be harmful, and (3) the report of a transgenic mouse with cardiomyopathy apparently caused by artificially high levels of mtDNA mutations in the heart. A recent report of a mouse with ubiquitously accelerated accumulation of mtDNA mutations and an array of phenotypes reminiscent of aging has abruptly overturned this consensus, with not only the authors but also many other expert commentators suggesting that the mtDNA mutation theory of aging has risen from the ashes. However, there are compelling reasons to doubt the relevance of this mouse to normal mammalian aging, and thus to seek further testing of specific mechanistic hypotheses for how mtDNA mutations could cause age-related dysfunction.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Mitochondrial mutations in mammalian aging: an over- hasty about-turn?

The very low abundance of mitochondrial DNA (mtDNA) mutations in nearly all mammalian tissues even in old age has led most mitochondriologists to reject the idea that such mutations might have a causal role in aging, despite the strong circumstantial (e.g. interspecies) evidence that they do have such a role, the promulgation since 1998 of two detailed mechanisms whereby low levels of mtDNA mut...

متن کامل

The mitochondrial DNA mutations associated with cardiac arrhythmia investigated in an LQTS family

Objective(s): As mitochondrial oxidative stress is probably entailed in ATP production, a candidate modifier factor for the long QT syndrome (LQTS) could be mitochondrial DNA (mtDNA). It has been notified that ion channels' activities in cardiomyocytes are sensitive to the ATP level. Materials and Methods: The sample of the research was an Iranian family with LQTS for mutations by PCR-SSCP and...

متن کامل

A Review of Mitochondrial Biogenesis and Cellular Response

Abstract Background and Objectives Mitochondrial biogenesis is a complex process involving the coordinated expression of mitochondrial and nuclear genes, the import of the products of the latter into the organelle and turnover of this process. Mitochondrial malfunction or defects in any of the many pathways involved in mitochondrial biogenesis can lead to degenerative diseases and possibly pla...

متن کامل

The Role of Mitochondrial DNA Mutations in Mammalian Aging

Mitochondrial DNA (mtDNA) accumulates both base-substitution mutations and deletions with aging in several tissues in mammals. Here, we examine the evidence supporting a causative role for mtDNA mutations in mammalian aging. We describe and compare human diseases and mouse models associated with mitochondrial genome instability. We also discuss potential mechanisms for the generation of these m...

متن کامل

Mitochondrial gene mutation screening in hearing loss patients, Hormozgan, Iran

Introduction: Hearing loss is the most frequent sensory disorder occurs in 1/1000 newborns. About 50% of hearing loss cases are due to genetic causes. Mutation in MTRNR1(A1555G), MTTL1(A3243G) and MTTS1(A7445G) are known to be one of the important cause of nonsyndromic Sensorineural hearing loos in some populations. This study aims to demonstrate the frequency of three mitochondrial mutatio...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Rejuvenation research

دوره 7 3  شماره 

صفحات  -

تاریخ انتشار 2004