Molecular Basis for Longevity
"Molecular Signatures of Longevity : Insights from Cross-Species Comparative Studies".
Seminars in Cell & Developmental Biology (07 Aug 2017) 70:190-203
http://europepmc.org/article/MED/28800931
"Putative lifespan-related traits and other features associated with longevity in exceptionally long-...-lived species".
"Summary of key findings from recent cross-species comparative studies".
"Gene expression is informative with regard to molecular features associated with longevity across species, but this is only one of the ways to assess these features. Two studies reported the analyses of metabolite and ion levels in brain, heart, kidney, and liver of 26 mammalian species across 10 taxonomic orders (Ma et al., 2015a; Ma et al., 2015b). Among the 162 water soluble metabolites and 100 lipids, positive correlation with species longevity traits was observed for sphingomyelins (in brain), whereas negative correlation was observed for amino acids (in brain), lysophosphatidyl-cholines (in brain and heart), lysophosphatidyl-ethanolamines (in brain and kidney), and triacylglycerols (in kidney) (Ma et al., 2015b). In particular, only those triacylglycerols with polyunsaturated fatty acid (PUFA) side chains showed significant negative correlation with species lifespan. A recent study on human plasma lipidomes of middle-aged offspring of nonagenarians revealed a signature of 19 lipid species associating with female familial longevity, including high levels of sphingomyelins and low levels of PUFA triacylglycerols (Gonzalez-Covarrubias et al., 2013). Analysis of phospholipids in heart of a number of mammals also revealed a negative correlation between double bond content and maximum lifespan (Pamplona et al., 2000). Naked mole rat tissues contain much lower levels of docosahexaenoic acid-containing (with 6 double bonds) phospholipids compared to mouse (Mitchell et al., 2007). Since PUFA are particularly sensitive to peroxidation damage (especially when present in membrane) (Hulbert, 2008), reduced level of polyunsaturated TAG in long-lived species may reflect their enhanced resistance to oxidative stress. Indeed, the peroxidation index for membrane composition is inversely correlated to longevity in mammals, birds, bivalve mollusks, honeybees and C. elegans (Hulbert et al., 2014).
In addition, high urate:allantoin ratio was observed among the long-lived species, which also expressed lower levels of uricase in liver (the enzyme that converts urate to allantoin). In fact, the uricase expression levels were exceptionally low in the naked mole rat, and this gene is a pseudogene in human and other higher primates (Ma et al., 2015b). The liver concentrations of two tryptophan degradation products, anthranilic acid and kynurenine, were also low among the long-lived species. Knockdown of the enzyme involved in breaking down tryptophan (tryptophan 2,3-dioxygenase, TDO) was shown to increase lifespan in C. elegans and fruit flies (Oxenkrug, 2010; van der Goot et al., 2012), whereas the kynurenine:tryptophan ratio in human increases with aging (Capuron et al., 2011).
In the ionome study, the levels of 18 elements in brain, heart, kidney and liver samples of the mammals were quantified by inductively-coupled plasma mass spectrometry. Each organ showed a distinctive pattern of ion distribution: lithium, sodium, and calcium levels were relatively high in kidney; phosphorus and potassium were high in brain; and 13 out of the 18 elements were high in liver (Ma et al., 2015a). In terms of correlation with longevity, zinc in kidney and liver showed significant positive correlation with species lifespan, although the effect was largely due to body mass."