| dc.description.abstract | Since Harman ' fîrst proposed that the mitochondria plays a role in the aging process, several
lines of research have been undertaken to support his theory. According to the theory, oxygen
free radicals are responsible for the age-associated decline in function at the cellular, tissue and
organ levels. The mitochondria use oxygen at a high rate, but due to a dysfunction in its usage of
oxygen the mitochondria releases oxygen free radicals, which exceeds the cellular antioxidant
defense. The mitochondrial genome, however, is extremely susceptible to oxidative damage and
DNA mutations, including deletions when compared to nuclear DNA. One of the causative
agents of this deletion(s) includes oxygen free radicals, by-product of ATP (energy) production.
The most frequent deletion associated with aging and diseases is known as “the common
deletion” or 4977 base pair (bp) deletion. In recent years a number of studies have been able to
detect mitochondrial DNA (mtDNA) deletions in various tissues from individuals over 20 years
of age. However, these studies were all cross-sectional in nature and the DNA sources were all
post-mitotic tissues such as muscle and brain. Mitotic tissues, such as blood were not used even
though acquiring blood is usually less invasive and would be more convenient to study the aging
process. Also, since aging occurs over time a longitudinal study design would be the most
appropriate model for the detection and quantification of mtDNA deletion(s). It has been well
documented that identical mtDNA is transmitted from mother to child at the point of conception,
and therefore monitoring the incidence of mtDNA deletion(s) by employing a maternal line
across several generations would mimic a longitudinal study model. Therefore, the first purpose
of this study is to mimic the benefits of a longitudinal study design by employing maternal lines
(3 & 4 generations) to establish mtDNA deletion(s) as a sensitive, specific and stable biomarker
for studying the aging process. The second purpose of this study is to determine the differences
in mtDNA deletions when comparing muscle and blood. There were 75 healthy participants with
age ranging from 8 months to 99 years. The participants provided 71 blood samples and 27 muscle biopsies. --from abstract. | |
