Do Mitochondrial DNA and Metabolic Rate Complement Each Other in Determination of the Mammalian Maximum Longevity?

Abstract

In animal cells, mitochondria are semiautonomous organelles of virtually "hostile" (bacterial) origin, with their own code and genome (mtDNA). The semiautonomy and restricted resources could result in occasional "conflicts of interests" with other cellular components, in which mitochondria have greater chances to be "the weakest link," thus limiting longevity. Two principal questions are addressed: (1) to what extent the mammalian maximum life span (MLS) is associated with mtDNA base composition? (2) Does mtDNA base composition correlate with another important mitochondria-associated variable-resting metabolic rate (RMR)-and whether they complement each other in determination of MLS? Analysis of 140 mammalian species revealed significant correlations between MLS and the content of the four mtDNA nucleotides, especially noted for GC pairs (r(2) = 0.42; p < 10(-17)). The most remarkable finding of this study is that multivariate stepwise analysis selected only the GC content and RMR, which together explained 77% of variation in MLS (p < 10(-25)). To the authors' knowledge, it is the highest coefficient of MLS determination that has ever been reported for a comparable sample size. Taking into account substantial errors in estimation of MLS and RMR, it could mean that the GC and RMR explain most of the MLS biological variation. Other putative players in MLS determination should have relatively small contribution or their effects should be realized via the same channels. Although further research is clearly warranted, the extraordinary high correlation of mtDNA GC and RMR with MLS suggests a "direct hitting" of the core longevity targets, inferring mitochondria as a primary object for longevity-promoting interventions.

Adaptive Threonine Increase in Transmembrane Regions of Mitochondrial Proteins in Higher Primates

“…The correlation at the AA level between the Thr composition in the hydrophobic region and the MLS in primates is intriguing, since many other factors to regulate longevity may be considered at a macroscopic level [32] and a recent study reports that the base composition of mtDNA, especially the G or GC content could undergo co-evolution with the mammalian longevity [33].…”

Biogerontology research in Israel

“…Another important finding is that both mitochondria-associated parameters, the GC content of mitochondrial DNA (mtDNA) as well as resting metabolic rate (RMR) are independent and powerful predictors of mammalian longevity (Lehmann et al 2008). Together, the mtDNA GC content and RMR explain over 75% of variation in mammalian maximum life span (MLS).…”

Biogerontology in Ukraine: update

“…The growing number of open access web databases and bulk of currently available phylogenetic information renders exciting possibilities in this field. In this regard, cooperation of groups from the State Institute of Gerontology in Kiev and the Ben-Gurion University of the Negev (Israel) seems noteworthy (Lehmann et al 2006(Lehmann et al , 2008Muradian et al 2010b). The two recent joint publications described below in more details demonstrate that much is comprehended, much more remains disputable, and even more is to be learned in this rewarding area.…”

“…When repeating lately the same kind analysis using data for 243 mammalian species available nowadays, virtually the same kind relations were found. Although further research is clearly warranted, the extraordinary high coefficient of determination of MLS suggests a ''direct hitting'' of the core longevity targets, inferring mitochondria as a primary object in longevity-promoting interventions (Lehmann et al 2008).…”