Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation

Lu, Junying; Simon, Matthew; Zhao, Yang; Ablaeva, Julia; Corson, Nancy; Choi, Yongwook; Yamada, KayLene Y.H.; Schork, Nicholas J.; Hood, Wendy R.; Hill, Geoffrey E.; Miller, Richard A.; Seluanov, Andrei; Gorbunova, Vera

doi:10.1016/j.cmet.2022.04.011

Cited by 47 publications

(31 citation statements)

References 140 publications

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“…Reinforcing this concept, the low expression of cystathionine β-synthase (CBS), as well as adenosyl methionine decarboxylase and spermidine synthase in long-lived mammalian species were recently demonstrated in a transcriptomic comparative study [39]. Consistent with our ndings, a global decrease of methionine and related metabolites was also found in long-lived y strains [48], worms [49], and mice [50].…”

Section: Discussionsupporting

confidence: 85%

“…Cell physiology and molecular composition are in uenced by speci c tightly regulated longevity-related gene expression patterns [35][36][37]. Diverse inter-species studies have reported the existence of species-speci c tissue transcriptomics [14,38,39], proteomics [40], lipidomics [3,41] and metabolomics [17,20,[42][43][44][45] pro les associated with animal longevity.…”

Section: Discussionmentioning

confidence: 99%

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Methionine metabolism is down-regulated in heart of long-lived mammals

Mota‐Martorell¹,

Jové²,

Berdún³

et al. 2022

Preprint

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Methionine constitutes a central hub of intracellular metabolic adaptations leading to an extended longevity (maximum lifespan). The present study follows a comparative approach analyzing methionine and related metabolites and amino acids profiles using a LC-MS/MS platform in heart from seven mammalian species with a longevity ranging from 3.8 to 57 years. Our findings demonstrate the existence of species-specific heart phenotypes associated with high longevity characterized by: i) low concentration of methionine and its related sulphur-containing metabolites; ii) low amino acid pool; and iii) low choline concentration. Our results support the existence of heart metabotypes characterized by a down-regulation in long-lived species, supporting the idea that in longevity less is more.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Methionine metabolism is down-regulated in heart of long-lived mammals

Mota‐Martorell¹,

Jové²,

Berdún³

et al. 2022

Preprint

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“…Specifically, the authors reported a reduced content of mTOR and Raptor, and identified phosphorylation patterns in mTOR and PRAS40 that might be consistent with a reduced mTORC1 activity in long-lived species. These results are supported by recently published transcriptomics data [ 25 ], and extend to other mammalian tissues. Again, the longevity-associated phenotype was associated with reduced mTORC1 core elements, such as mtor and rptor ; downstream effectors such as rps6kb1 (S6K1); and its negative regulators akt1s1 (PRAS40) and fkbp1a (FKBP12).…”

Section: Mtorc1 and Longevitysupporting

confidence: 89%

“…In fact, apart from having a role in determining species longevity, the mTOR signalling pathway seems to be a key determinant of individual longevity [ 5 ]. Accordingly, reduced activity of the mTOR signalling network has been reported in tissues from exceptionally long-lived rodents [ 22 , 23 ], whales [ 24 ], and other mammals [ 25 ].…”

Section: Mtorc1 and Longevitymentioning

confidence: 99%

“…These adaptations evolved by maintaining lowered steady-state levels of mTORC1 content or activity [ 14 , 25 , 26 , 33 , 34 ], reducing the content of mTORC1 upstream regulators [ 14 , 25 , 26 , 28 ], or lowering the activation of its downstream effectors [ 14 , 22 , 23 , 25 , 29 , 30 ]. Furthermore, these regulations operate at all expression levels, either genes [ 14 , 25 , 26 ], proteins [ 14 , 22 , 23 ], or metabolites [ 14 ]. Apart from the metabolic effects resulting from a reduced pathway activity, reduced mTORC1 is essential to maintaining its integrity [ 35 ].…”

Section: Mtorc1 and Longevitymentioning

confidence: 99%

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mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity

Mota‐Martorell

Jové

Pamplona

2022

IJMS

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Decreased content and activity of the mechanistic target of rapamycin (mTOR) signalling pathway, as well as the mTOR complex 1 (mTORC1) itself, are key traits for animal species and human longevity. Since mTORC1 acts as a master regulator of intracellular metabolism, it is responsible, at least in part, for the longevous phenotype. Conversely, increased content and activity of mTOR signalling and mTORC1 are hallmarks of ageing. Additionally, constitutive and aberrant activity of mTORC1 is also found in age-related diseases such as Alzheimer’s disease (AD) and cancer. The downstream processes regulated through this network are diverse, and depend upon nutrient availability. Hence, multiple nutritional strategies capable of regulating mTORC1 activity and, consequently, delaying the ageing process and the development of age-related diseases, are under continuous study. Among these, the restriction of calories is still the most studied and robust intervention capable of downregulating mTOR signalling and feasible for application in the human population.

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Promoting longevity with less cancer: The 2022 International Conference on Aging and Cancer

Cui,

Wang,

Jiang

et al. 2023

Aging and Cancer

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Aging and cancer are increasingly becoming big challenges for public health worldwide due to increased human life expectancy. Meanwhile, aging is one of the major risk factors for cancer. In December 2019, the first International Conference on Aging and Cancer was held in Haikou, Hainan province (island), China, preluding the establishment of the International Center for Aging and Cancer (ICAC) at Hainan, an institute dedicated to the research at the intersection of aging and cancer. Since then, the ICAC has hosted the annual conference each December in Hainan. The 2022 ICAC conference, with the theme of “promoting longevity with less cancer,” invited 17 internationally renowned scientists to share their new research and insights. Topics included DNA methylation in rejuvenation, development, and cellular senescence; lifespan regulation and longevity manipulation; metabolism and aging; cellular senescence and diseases; and novel therapeutics for cancer and antiaging/anticancer drug discovery. The forum highlighted the interconnectedness of aging and senescence with cancer evolution and risk. Although there is hope for preventing diseases like cancer by modulating systems that also control lifespan, attention has to be paid to the conflicting needs and competing demands in human biology.

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Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation

Cited by 47 publications

References 140 publications

Methionine metabolism is down-regulated in heart of long-lived mammals

Methionine metabolism is down-regulated in heart of long-lived mammals

mTOR Complex 1 Content and Regulation Is Adapted to Animal Longevity

Promoting longevity with less cancer: The 2022 International Conference on Aging and Cancer

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