Organization of the Mammalian Metabolome according to Organ Function, Lineage Specialization, and Longevity

Ma, Siming; Yim, Sun Hee; Lee, Sang Goo; Kim, Eun Bae; Lee, Sang Rae; Chang, Kyu Tae; Buffenstein, Rochelle; Lewis, Kaitlyn N.; Park, Thomas J.; Miller, Richard A.; Clish, Clary B.; Gladyshev, Vadim N.

doi:10.1016/j.cmet.2015.07.005

Cited by 106 publications

(142 citation statements)

References 81 publications

Supporting

Mentioning

126

Contrasting

Unclassified

Order By: Relevance

“…A recent breakthrough study on mammals' metabolomes has highlighted the power of metabolomics to predict markers associated with organ specialization in a phylogenetic context (48). Future directions will make use of genomics resources existing for related species of N. attenuata to extend the approach to the diagnosis of gene divergence effects contributing the most to tissue-metabolic specialization.…”

Section: Resultsmentioning

confidence: 99%

Illuminating a plant’s tissue-specific metabolic diversity using computational metabolomics and information theory

Heiling

Baldwin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Secondary metabolite diversity is considered an important fitness determinant for plants' biotic and abiotic interactions in nature. This diversity can be examined in two dimensions. The first one considers metabolite diversity across plant species. A second way of looking at this diversity is by considering the tissue-specific localization of pathways underlying secondary metabolism within a plant. Although these cross-tissue metabolite variations are increasingly regarded as important readouts of tissue-level gene function and regulatory processes, they have rarely been comprehensively explored by nontargeted metabolomics. As such, important questions have remained superficially addressed. For instance, which tissues exhibit prevalent signatures of metabolic specialization? Reciprocally, which metabolites contribute most to this tissue specialization in contrast to those metabolites exhibiting housekeeping characteristics? Here, we explore tissue-level metabolic specialization in Nicotiana attenuata, an ecological model with rich secondary metabolism, by combining tissue-wide nontargeted mass spectral data acquisition, information theory analysis, and tandem MS (MS/MS) molecular networks. This analysis was conducted for two different methanolic extracts of 14 tissues and deconvoluted 895 nonredundant MS/MS spectra. Using information theory analysis, anthers were found to harbor the most specialized metabolome, and most unique metabolites of anthers and other tissues were annotated through MS/MS molecular networks. Tissuemetabolite association maps were used to predict tissue-specific gene functions. Predictions for the function of two UDP-glycosyltransferases in flavonoid metabolism were confirmed by virus-induced gene silencing. The present workflow allows biologists to amortize the vast amount of data produced by modern MS instrumentation in their quest to understand gene function.secondary metabolism | mass spectrometry | metabolomics | information theory | Nicotiana attenuata P lants are elegant synthetic chemists making use of their metabolic prowess to produce complex blends of structurally diverse chemicals. Commonly quoted estimates state that plants produce somewhere on the order of 200,000 chemical structures. Secondary metabolites, also referred to as specialized metabolites or natural products, contribute to the largest fraction of this structural diversity. Compared with their counterparts in central metabolism (primary metabolites), secondary metabolite groups have diversified to the extreme in plant lineages, likely as a result of the multiple ecological roles they fulfill (1). The high degree of plasticity of secondary metabolism pathways is consistent with the existence of large families of metabolism-related genes such as cytochrome P450s and UDP-glycosyltransferases in plant genomes that can create structural and chemical modifications almost without limits. The majority of metabolic gene functions remain unknown, however, either because the metabolites that they produce are unknown or signi...

show abstract

Section: Resultsmentioning

confidence: 99%

Illuminating a plant’s tissue-specific metabolic diversity using computational metabolomics and information theory

Heiling

Baldwin

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The trait data were log‐transformed and standardized. Four models of trait evolution were tested: (i) complete absence of phylogenetic relationship (“Null”); (ii) Brownian motion model (“BM”); (iii) BM transformed by Pagel's lambda (“Lambda”); and (iv) Ornstein–Uhlenbeck model (“OU”; Felsenstein, 1985; Lavin, Karasov, Ives, Middleton & Garland, 2008; Ma et al., 2015; Martins & Hansen, 1997; Pagel, 1999). These models describe the relationship among the regression residuals of the species.…”

Section: Methodsmentioning

confidence: 99%

Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity

Avanesov

Porter

et al. 2018

Aging Cell

Self Cite

View full text Add to dashboard Cite

SummaryLifespan varies dramatically among species, but the biological basis is not well understood. Previous studies in model organisms revealed the importance of nutrient sensing, mTOR, NAD/sirtuins, and insulin/IGF1 signaling in lifespan control. By studying life‐history traits and transcriptomes of 14 Drosophila species differing more than sixfold in lifespan, we explored expression divergence and identified genes and processes that correlate with longevity. These longevity signatures suggested that longer‐lived flies upregulate fatty acid metabolism, downregulate neuronal system development and activin signaling, and alter dynamics of RNA splicing. Interestingly, these gene expression patterns resembled those of flies under dietary restriction and several other lifespan‐extending interventions, although on the individual gene level, there was no significant overlap with genes previously reported to have lifespan‐extension effects. We experimentally tested the lifespan regulation potential of several candidate genes and found no consistent effects, suggesting that individual genes generally do not explain the observed longevity patterns. Instead, it appears that lifespan regulation across species is modulated by complex relationships at the system level represented by global gene expression.

show abstract

“…However, whether AMPK signaling is modulated in long-lived species is unknown. Since long-lived species have unique metabolic signatures [117], it would be interesting to test the status of the AMPK signaling pathway.…”

Section: Other Lifespan-modulating Mechanisms Identified In Model Orgmentioning

confidence: 99%

Molecular Mechanisms Determining Lifespan in Short- and Long-Lived Species

Tian

Seluanov

Gorbunova

2017

Trends in Endocrinology & Metabolism

View full text Add to dashboard Cite

Aging is a global decline of physiological functions, leading to an increased susceptibility to diseases and ultimately death. Maximum lifespans differ up to 200-fold between mammalian species. Although considerable progress has been achieved in identifying conserved pathways that regulate individual lifespan within model organisms, whether the same pathways are responsible for the interspecies differences in longevity remains to be determined. Recent cross-species studies have begun to identify pathways responsible for interspecies differences in lifespan. Here, we review the evidence supporting the role of anti-cancer mechanisms, DNA repair machinery, insulin/IGF1 signaling, and proteostasis in defining species lifespans. Understanding the mechanisms responsible for the dramatic differences in lifespan between species will have a transformative effect on developing interventions to improve human health and longevity.

show abstract

Organization of the Mammalian Metabolome according to Organ Function, Lineage Specialization, and Longevity

Cited by 106 publications

References 81 publications

Illuminating a plant’s tissue-specific metabolic diversity using computational metabolomics and information theory

Illuminating a plant’s tissue-specific metabolic diversity using computational metabolomics and information theory

Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity

Molecular Mechanisms Determining Lifespan in Short- and Long-Lived Species

Contact Info

Product

Resources

About