Here I'll point out a recent addition to the set of open data interfaces that are both interesting and relevant to aging research: the MitoAge database, cataloging mitochondrial DNA and longevity in a wide range of species. Mitochondria, the descendants of ancient symbiotic bacteria, swarm in herds inside our cells. The research of past years provides compelling data to suggest that the details of mitochondrial composition, particularly in respect to their resistance to oxidative damage, has a fair-sized effect on life span. Why is oxidative damage an important consideration? Because mitochondria work to create energy store molecules used to power the rest of the cell, a process that involves the generation of reactive oxidizing molecules as a side-effect. A cell is a fluid sack of structures and chemical reactions, all of these components moving around in close proximity, engaged in constant activity. Newly created oxidants don't have far to go in order to react with some important piece of molecular machinery in a way that causes damage and dysfunction. Some are rendered harmless by natural antioxidants, but damage is constant and ongoing, albeit usually repaired very rapidly.
The closest structure for mitochondrially generated oxidants to react with and harm is the mitochondrion itself, and in particular its DNA. Every mitochondrion has at least one copy of the left-over remnant genome from its bacterial ancestry, encoding necessary proteins used in its structure and energy store construction machinery. This DNA isn't as well protected and repaired as is nuclear DNA, and certain rare forms of damage can produce mitochondria that are both dysfunctional and more likely to replicate and survive within their cell. It isn't completely open and shut that this is the way in which cells become overtaken by broken mitochondria and go on to harm surrounding cells and tissues; this contribution to the aging process might have more to do with errors in mitochondrial replication than oxidative damage, for example. But there is certainly a good solid correlation in mammals between longevity and mitochondrial resistance to oxidative damage. When we look at birds and bats, the details of their mitochondrial biochemistry is entwined with the metabolic requirements of flight, and the comparatively long life spans in these species when considering their size may once again be a factor of adaptation to higher levels of oxidative stress generated during flight. Further, there are the studies showing modestly increased health or life span in mice due to increased levels of natural mitochondrial antioxidants, or mitochondrially targeted antioxidant drugs.
To my eyes all of this work and knowledge as a whole should really be taken as a big pointer to suggest that repair of damaged mitochondria is an important part of any future regenerative medicine to produce rejuvenation. The SENS Research Foundation has helped to pioneer the allotopic expression approach to maintaining undamaged mitochondria that is currently under clinical development for inherited mitochondrial disease at Gensight, and continues to work towards a more comprehensive version of the treatment that can be used to treat aging. Funding - as ever - is very limited for this line of research given the potential benefits, but the fastest path to results remains to get this working in mice and see what happens. Given what we know of the effects of more subtle and limited manipulations in mitochondrial biochemistry, we should probably expect the benefits to health and longevity to be sizable enough to draw attention.
The rapidly increasing number of species with fully sequenced mitochondrial DNA (mtDNA), together with accumulated data on longevity records, provide new fascinating opportunities for the analysis of the links between mtDNA features and longevity across animals. To facilitate such an analysis, and to support the scientific community in carrying it out, we developed MitoAge - a curated, publicly available database, containing an extensive collection of calculated mtDNA data records, and integrated it with longevity records. The MitoAge website also provides the basic tools for comparative analysis of mtDNA, with a special focus on animal longevity.
Mitochondria are the most "hard-working" organelles and the only organelles in the animal cell that have their own genome. They have long been considered one of the major players in the mechanisms of aging, longevity and age-related diseases1. We and others have shown strong correlative links between mammalian maximum lifespan and mtDNA base composition. In particular, the mtDNA GC content appears to be an independent and powerful predictor of mammalian longevity.
The stability of the mitochondrial DNA (mtDNA) is vital for mitochondrial proper functioning; therefore, changes in mtDNA may have far-reaching consequences for the cell fate and, ultimately, for the whole organism. Not surprisingly, due to a key role in energy production, generation of damaging factors (ROS, heat), and regulation of apoptosis, mitochondria and mtDNA in particular have long been considered one of the major players in the mechanisms of aging, longevity and age-related diseases.
We developed the MitoAge database containing calculated mtDNA compositional features of the entire mitochondrial genome, mtDNA coding (tRNA, rRNA, protein-coding genes) and non-coding (D-loop) regions, and codon usage/amino acids frequency for each protein-coding gene. MitoAge includes 922 species with fully sequenced mtDNA and maximum lifespan records. The database is available through the MitoAge website, which provides the necessary tools for searching, browsing, comparing and downloading the data sets of interest for selected taxonomic groups across the Kingdom Animalia. The MitoAge website assists in statistical analysis of different features of the mtDNA and their correlative links to longevity.