(mtDNA) base composition correlates with animal species maximum life span. The mitochondrial DNA base composition is thought to reflect its nucleotide-specific (guanine, cytosine, thymidine and adenine) different mutation rates (i.e., accumulation of guanine in the mitochondrial DNA of an animal species is due to low guanine mutation rate in the mitochondria of that species). Centenarians Lymphoblastoid cell lines established from blood samples of humans who lived past 100 years (centenarians) have significantly higher activity of the DNA repair protein Poly (ADP-ribose) polymerase (PARP) than cell lines from younger individuals (20 to 70 years old). The lymphocytic cells of centenarians have characteristics typical of cells from young people, both in their capability of priming the mechanism of repair after H2O2 sublethal oxidative DNA damage and in their PARP capacity. Menopause As women age, they experience a decline in reproductive performance leading to menopause. This decline is tied to a decline in the number of ovarian follicles. Although 6 to 7 million oocytes are present at mid-gestation in the human ovary, only about 500 (about 0.05%) of these ovulate, and the rest are lost. The decline in ovarian reserve appears to occur at an increasing rate with age, and leads to nearly complete exhaustion of the reserve by about age 51. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors resulting in chromosomally abnormal conceptions. BRCA1 and BRCA2 are homologous recombination repair genes. The role of declining ATM-Mediated DNA double strand DNA break (DSB) repair in oocyte aging was first proposed by Kutluk Oktay, MD, PhD based on his observations that women with BRCA mutations produced fewer oocytes in response to ovarian stimulation repair. His laboratory has further studied this hypothesis and provided an explanation for the decline in ovarian reserve with age. They showed that as women age, double-strand breaks accumulate in the DNA of their primordial follicles. Primordial follicles are immature primary oocytes surrounded by a single layer of granulosa cells. An enzyme system is present in oocytes that normally accurately repairs DNA double-strand breaks. This repair system is referred to as homologous recombinational repair, and it is especially active during meiosis. Titus et al. from Oktay Laboratory also showed that expression of four key DNA repair genes that are necessary for homologous recombinational repair (BRCA1, MRE11, Rad51 and ATM) decline in oocytes with age. This age-related decline in