Mitochondrial dysfunction is a major hallmark of aging. Mitochondrial DNA (mtDNA) mutations (inherited or acquired) may cause a malfunction of the respiratory chain (RC), and thus negatively affect cell metabolism and function. In contrast, certain mtDNA single nucleotide polymorphisms (SNPs) may be beneficial to mitochondrial electron transport chain function and the extension of cellular health as well as lifespan. The goal of the MitoAging project is to detect key physiological characteristics and mechanisms that improve mitochondrial function and use them to develop therapies to increase longevity and a healthy lifespan. We chose to perform a systematic literature review (SLR) as a tool to collect key mtDNA SNPs associated with an increase in lifespan. Then validated our results by comparing them to the MitoMap database. Next, we assessed the effect of relevant SNPs on protein stability. A total of 28 SNPs were found in protein coding regions. These SNPs were reported in Japan, China, Turkey, and India. Among the studied SNPs, the C5178A mutation in the ND2 gene of Complex I of the RC was detected in all the reviewed reports except in Uygur Chinese centenarians. Then, we found that G9055A (ATP6 gene) and A10398G (ND3 gene) polymorphisms have been associated with a protective effect against Parkinson's disease (PD). Additionally, C8414T in ATP8 was significantly associated with longevity in three Japanese reports. Interestingly, using MitoMap we found that G9055A (ATP6 gene) was the only SNP promoting longevity not associated with any pathology. The identification of SNPs associated with an increase in lifespan opens the possibility to better understand individual differences regarding a decrease in illness susceptibility and find strategies that contribute to healthy aging.
Bibliographical noteFunding Information:
We thank the School of Medicine at the Universidad San Francisco de Quito, USFQ, the “Instituto de Investigaciones en Biomedicina, USFQ”, and the Mito-Act Research Consortium in Quito, Ecuador for their constant support of our work and initiatives. We would also like to thank Kevin Zambrano and Diego Barba for their help revising this paper. Protein structure graphics performed with UCSF Chimera, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from NIH P41-GM103311. VC is thankful to her grandfather Fausto Pérez for his kindness and wisdom. AH is grateful towards her grandfather Ramil Haro for instilling the love for science in her; and her parents Karina Vinueza and Jorge Haro for the support and love. IS is thankful to Lesly and Marco for their unconditional support. AC is thankful to María Luisa and Diego for their love and support.
© 2022 Elsevier B.V. and Mitochondria Research Society
- Mitochondrial DNA
- Mitochondrial protein