The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity

Chaudhari, Snehal N.; Kipreos, Edward T.

doi:10.1002/bies.201800005

Cited by 24 publications

(28 citation statements)

References 131 publications

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“…Lipofuscin formation, iron sequestration, and LD formation all occur as a result of and contribute to ROS accumulation, which is known to be a result of mitochondrial dysfunction. These data suggest that metabolic impairment may be the driver of these aging hallmarks, as suggested in the Energy Maintenance Theory of Aging ( Chaudhari and Kipreos, 2018 ) and the Free-Radical-Induced Energetic and Neural Decline in Senescence (FRIENDS) theory of aging ( Raz and Daugherty, 2018 ).…”

Section: Discussionmentioning

confidence: 69%

Changes in Metabolism and Proteostasis Drive Aging Phenotype in Aplysia californica Sensory Neurons

Kron

Schmale

Fieber

2020

Front. Aging Neurosci.

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Aging is associated with cognitive declines that originate in impairments of function in the neurons that make up the nervous system. The marine mollusk Aplysia californica (Aplysia) is a premier model for the nervous system uniquely suited to investigation of neuronal aging due to uniquely identifiable neurons and molecular techniques available in this model. This study describes the molecular processes associated with aging in two populations of sensory neurons in Aplysia by applying RNA sequencing technology across the aging process (age 6–12 months). Differentially expressed genes clustered into four to five coherent expression patterns across the aging time series in the two neuron populations. Enrichment analysis of functional annotations in these neuron clusters revealed decreased expression of pathways involved in energy metabolism and neuronal signaling, suggesting that metabolic and signaling pathways are intertwined. Furthermore, increased expression of pathways involved in protein processing and translation suggests that proteostatic stress also occurs in aging. Temporal overlap of enrichment for energy metabolism, proteostasis, and neuronal function suggests that cognitive impairments observed in advanced age result from the ramifications of broad declines in energy metabolism.

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Section: Discussionmentioning

confidence: 69%

Changes in Metabolism and Proteostasis Drive Aging Phenotype in Aplysia californica Sensory Neurons

Kron

Schmale

Fieber

2020

Front. Aging Neurosci.

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“…Another key metabolic change is that mitochondria become fragmented and lose volume (Yasuda et al, 2006; Regmi et al, 2014) with a concurrent loss of electron chain oxygen consumption and ATP production (Braeckman et al, 2002; Houthoofd et al, 2005). Mitochondrial damage is also a hallmark of human aging (Chaudhari and Kipreos, 2018) and can be delayed using interventions that prolong life (Houthoofd et al, 2005; Brys et al, 2010). Various age-related pathologies can be observed in worms after the time of sperm depletion and are fully evident prior to median lifespan (Ezcurra et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During C. elegans Aging

Hastings

Mains

Virk

et al. 2019

Front. Mol. Biosci.

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In this contribution, we describe a multi-omics systems biology study of the metabolic changes that occur during aging in Caenorhabditis elegans. Sampling several time points from young adulthood until early old age, our study covers the full duration of aging and include transcriptomics, and targeted MS-based metabolomics. In order to focus on the metabolic changes due to age we used two strains that are metabolically close to wild-type, yet are conditionally non-reproductive. Using these data in combination with a whole-genome model of the metabolism of C. elegans and mathematical modeling, we predicted metabolic fluxes during early aging. We find that standard Flux Balance Analysis does not accurately predict in vivo measured fluxes nor age-related changes associated with the Citric Acid cycle. We present a novel Flux Balance Analysis method where we combined biomass production and targeted metabolomics information to generate an objective function that is more suitable for aging studies. We validated this approach with a detailed case study of the age-associated changes in the Citric Acid cycle. Our approach provides a comprehensive time-resolved multi-omics and modeling resource for studying the metabolic changes during normal aging in C. elegans.

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“…[1] Along with the substantial evidence from their own work on C. elegans and studies on other model animals, the logic of the authors' argument is clear: first, aging is closely associated with the mitochondria's well-being; second, nine of ten lifespan extension pathways in C. elegans are associated with elongation of mitochondria via fusion, and elongated mitochondria are more efficient in producing ATP. [1] Along with the substantial evidence from their own work on C. elegans and studies on other model animals, the logic of the authors' argument is clear: first, aging is closely associated with the mitochondria's well-being; second, nine of ten lifespan extension pathways in C. elegans are associated with elongation of mitochondria via fusion, and elongated mitochondria are more efficient in producing ATP.…”

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confidence: 99%

Comparing the New and Existing Hypotheses on Energy Metabolism and Longevity

Hou

2018

BioEssays

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In this issue of BioEssays, Chaudhari and Kipreos hypothesize that mitochondrial fusion promotes survival, especially in old animals, through the mechanism of maintaining energy metabolism. [1] Along with the substantial evidence from their own work on C. elegans and studies on other model animals, the logic of the authors' argument is clear: first, aging is closely associated with the mitochondria's well-being; second, nine of ten lifespan extension pathways in C. elegans are associated with elongation of mitochondria via fusion, and elongated mitochondria are more efficient in producing ATP. Interestingly, the 10th pathway upregulates alternate energy generating pathways; third, maintaining ATP levels and energy metabolism supports longevity.Practitioners in the relevant fields may have three questions about this hypothesis. Chaudhari and Kipreos well address them in the paper.First, the hypothesis suggests a positive correlation between enhanced energy metabolism and lifespan extension, which is seemingly opposite to the long-standing observation of the negative correlation between energy metabolism and lifespan. Across species, the animals with high mass-specific energy consumption live shorter. Many researchers believe that high energy production may lead to higher reactive oxygen species (ROS) production, which causes oxidative stress and shortens lifespan. Also, caloric restriction (CR) extends lifespan, but does not lower energy consumption greatly.As cited in Chaudhari and Kipreos, the results from Hou et al. [2,3] have suggested that cellular damage is insensitive to the change in total energy consumption. It is the energy allocation to damage repair (or maintenance in general) that largely influences the damage level and aging rate. In the case of CR, while it negligibly alters animals' metabolic rate, CR channels more energy to maintenance through suppressing biosynthesis. [3] Along this line, Chaudhari and Kipreos further elaborated on how energy allocated to maintenance would allow the cell to maintain repair and homeostatic mechanisms, such as proteostasis and mitochondrial biogenesis.Second, in the last two decades, the importance of mitochondrial proton leak (uncoupling) in cellular damage and aging has been highlighted by multiple researchers, e.g., Ref. [4]. At the first glance, the "uncoupling to survive hypothesis" may conflict with Chaudhari and Kipreos' hypothesis, because uncoupling causes a decrease in ATP production, but fusion increases ATP production.Analyzing the data from mice, [4] as well as the data from human cells in culture and yeast, Chaudhari and Kipreos give convincing argument that mild uncoupling, which extends lifespan, is correlated with greater mitochondrial respiration and higher ATP levels. They conclude that "the linkage between uncoupling and lifespan/healthspan is in the context of increased metabolic intensity." Thus, these two hypotheses are compatible.Third, Barja has championed the idea that the mitochondrial ROS production is the key to understanding how empiri...

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The Energy Maintenance Theory of Aging: Maintaining Energy Metabolism to Allow Longevity

Cited by 24 publications

References 131 publications

Changes in Metabolism and Proteostasis Drive Aging Phenotype in Aplysia californica Sensory Neurons

Changes in Metabolism and Proteostasis Drive Aging Phenotype in Aplysia californica Sensory Neurons

Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During C. elegans Aging

Comparing the New and Existing Hypotheses on Energy Metabolism and Longevity

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