Manipulating Cellular Energetics to Slow Aging of Tissues and Organs

Sokolov, Svyatoslav S.; Severin, Fedor F.

doi:10.1134/s0006297920060024

Cited by 4 publications

(3 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The signaling process concerning whether to degrade a protein is affected in part by the availability of ATP in the cell. Decline of cellular energetics with age and disruption of fatty acid and glucose metabolism decreases the amount of available ATP and changes chaperone activity, leading to the accumulation of damaged proteins [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components

et al. 2021

View full text Add to dashboard Cite

Differentially expressed (DE) proteins in the cortical microvessels (MVs) of young, middle-aged, and old male and female mice were evaluated using discovery-based proteomics analysis (> 4,200 quantified proteins/group). Most DE proteins (> 90%) showed no significant differences between the sexes; however, some significant DE proteins showing sexual differences in MVs decreased from young (8.3%), to middle-aged (3.7%), to old (0.5%) mice. Therefore, we combined male and female data for age-dependent comparisons but noted sex differences for examination. Key proteins involved in the oxidative stress response, mRNA or protein stability, basement membrane (BM) composition, aerobic glycolysis, and mitochondrial function were significantly altered with aging. Relative abundance of superoxide dismutase-1/-2, catalase and thioredoxin were reduced with aging. Proteins participating in either mRNA degradation or pre-mRNA splicing were significantly increased in old mice MVs, whereas protein stabilizing proteins decreased. Glycolytic proteins were not affected in middle age, but the relative abundance of these proteins decreased in MVs of old mice. Although most of the 41 examined proteins composing mitochondrial complexes I–V were reduced in old mice, six of these proteins showed a significant reduction in middle-aged mice, but the relative abundance increased in fourteen proteins. Nidogen, collagen, and laminin family members as well as perlecan showed differing patterns during aging, indicating BM reorganization starting in middle age. We suggest that increased oxidative stress during aging leads to adverse protein profile changes of brain cortical MVs that affect mRNA/protein stability, BM integrity, and ATP synthesis capacity.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components

et al. 2021

View full text Add to dashboard Cite

show abstract

“…A mild decrease in the ATP/ADP ratio can be beneficial for cells [ 1 ]. Such a decrease could be achieved by various means, i.e., by adding chemicals dissipating mitochondrial membrane potential [ 1 , 2 ], moderating the mitochondrial respiratory machinery [ 3 ] or decreasing the rate of glycolysis (reviewed in [ 4 ]). Such chemicals are promising drugs for treating obesity; they also can be considered as caloric restriction mimetics.…”

Section: Introductionmentioning

confidence: 99%

Lipophilic Cations Rescue the Growth of Yeast under the Conditions of Glycolysis Overflow

et al. 2020

View full text Add to dashboard Cite

Chemicals inducing a mild decrease in the ATP/ADP ratio are considered as caloric restriction mimetics as well as treatments against obesity. Screening for such chemicals in animal model systems requires a lot of time and labor. Here, we present a system for the rapid screening of non-toxic substances causing such a de-energization of cells. We looked for chemicals allowing the growth of yeast lacking trehalose phosphate synthase on a non-fermentable carbon source in the presence of glucose. Under such conditions, the cells cannot grow because the cellular phosphate is mostly being used to phosphorylate the sugars in upper glycolysis, while the biosynthesis of bisphosphoglycerate is blocked. We reasoned that by decreasing the ATP/ADP ratio, one might prevent the phosphorylation of the sugars and also boost bisphosphoglycerate synthesis by providing the substrate, i.e., inorganic phosphate. We confirmed that a complete inhibition of oxidative phosphorylation alleviates the block. As our system includes a non-fermentable carbon source, only the chemicals that did not cause a complete block of mitochondrial ATP synthesis allowed the initial depletion of glucose followed by respiratory growth. Using this system, we found two novel compounds, dodecylmethyl diphenylamine (FS1) and diethyl (tetradecyl) phenyl ammonium bromide (Kor105), which possess a mild membrane-depolarizing activity.

show abstract

“…Many such studies use experimental models, such as Drosophila melanogaster (fruit flies), C. elegans (worms) and mice. These studies have shown that age increases defects in genetic and protein networks, leading to a functional and structural decline of the myocardium and vasculature, due partly to increased sensitivity of the cardiovascular system to oxidative stress and inflammation [1] . Increased anabolic energy metabolism is associated with decreased longevity, indicating that decreasing anabolic metabolism, thus increasing the catabolic breakdown of stored nutrients, should extend lifespan [2] .…”

mentioning

confidence: 99%

Hydrogen sulfide: the gas that fuels longevity

Blackwood¹,

Glembotski²

2022

J Cardiovasc Aging

View full text Add to dashboard Cite

The molecular determinants of lifespan can be examined in animal models with the long-term objective of applying what is learned to the development of strategies to enhance longevity in humans. Here, we comment on a recent publication examining the molecular mechanisms that determine lifespan in worms, Caenorhabditis elegans (C. elegans), where it was shown that inhibiting protein synthesis increased levels of the transcription factor, ATF4. Gene expression analyses showed that ATF4 increased the expression of genes responsible for the formation of the gas, hydrogen sulfide (H2S). Further examination showed that H2S increased longevity in C. elegans by modifying proteins in ways that stabilize their structures and enhance their functions. H2S has been shown to improve cardiovascular performance in mouse models of heart disease, and clinical trials are underway to test the effects of H2S on cardiovascular health in humans. These findings support the concept that nutrient deprivation, which slows protein synthesis and leads to ATF4-mediated H2S production, may extend lifespan by improving the function of the cardiovascular system and other systems that influence longevity in humans.

show abstract

Manipulating Cellular Energetics to Slow Aging of Tissues and Organs

Cited by 4 publications

References 78 publications

Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components

Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components

Lipophilic Cations Rescue the Growth of Yeast under the Conditions of Glycolysis Overflow

Hydrogen sulfide: the gas that fuels longevity

Contact Info

Product

Resources

About