Year: 2003
Type: article
Abstract: We agree with much of what Dr Jacobs argues but would like to comment on some of his statements.He makes many valid comments, comments that were very relevant 4 -5 years ago.Studies based on tissue homogenates are, as he mentions, very difficult to interpret and it is exceedingly difficult to correlate mitochondrial changes with physiological outcomes based on those experiments.We would, however, argue that advances in methodologies along with increased attention to the fate of specific cells has greatly enhanced our ability to link changes in the mitochondrial genome with the aging process.The relatively high abundance of cells affected in the mitochondrial myopathies makes it much easier to envision how cellular dysfunction results in tissue dysfunction in these human diseases.The lower frequency of cells affected by mtDNA deletion mutations in aging tissues has resulted in many researchers questioning whether these mtDNA deletion mutations have any physiological relevance.In the past few years, however, there has been a considerable shift in experimental design.Instead of focusing on tissue homogenates, studies have emphasized the analysis of individual cells.These studies indicate that mtDNA deletion mutations and single nucleotide mutations clonally accumulate to high levels within single cells.Our studies indicate that mitochondrial DNA deletion mutations have a physiological impact on skeletal muscle, leading to fibre atrophy and, ultimately, loss of the cells.Rather than rely on in vitro approaches to the analysis of the role of mtDNA mutations in the aging process, we have taken a two-pronged approach in our in vivo studies.The nature of the mutation event and accumulation makes it impossible to identify and then follow a specific mutation event with time (due to the focal and segmental accumulation of the mutations).We use two different animal models, rhesus monkeys and rats, and follow both through aging.For the rhesus monkeys, muscle biopsies are collected at 3-year intervals.
Source: Aging Cell
Institution: University of Wisconsin–Madison
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2035973775