PerspectiveSTEM CELLS

Holding your breath for longevity

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Science  20 Mar 2015:
Vol. 347, Issue 6228, pp. 1319-1320
DOI: 10.1126/science.aaa9608

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  • The secret of longevity
    • Qiuyun Liu, Professor, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
    • Other Contributors:
      • Hongyu Zhong, student, Department of Infection, Immunity & Cardiovascular Disease, Medical School, University of Sheffield, Sheffield, UK
      • Jing Li, Student, Department of Genetics and Biochemistry, Clemson University, USA
      • Yan Huang, Student, Hong Kong University of Science and Technology, Hong Kong
      • Xiaoxuan Wu, Student, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
      • Bo Yu, Researcher, Department of Cell and Molecular Biology, Tulane University, USA

    Dehydroepiandrosterone (DHEA) is the precursor of testosterone and estrogen, which may sustain and enhance the activities of respiratory chain and to some extent the activities of the Krebs cycle. The drop in DHEA level with age may tick away the minutes of our lives as the activities of the respiratory chain decline in seniors. Krebs cycle is one of the major sources of organic acids such as oxalate. Oxalate forms insoluble salts with numerous metal ions which are stressful to cells (1-2). Compounds with similar structures to oxalate, such as ethanol, acetic acid could extend lifespan after moderate intake (3-4). The moderate carcinogenic risks of testosterone and estrogen intake may be associated with enhanced proton production via augmented Krebs cycle (5-7). Glucose-6-phosphate dehydrogenase (G6PD) mutations have been found in some centenarians (8), and the enzyme variants cannot form fructose 6-phosphate that is the precursor of oxaloacetate giving rise to oxalate.
    Calcium intake has been reported to reduce cancer risks (9), which can be attributed to its neutralizing effects to locally formed HCl (5-7). Chinese-based vinegar factories are virtually cancer free (6), as volatile acetic acid can antagonize HCl. Although ethanol can extend lifespan, its carcinogenic property to sensitive people after overconsumption is a concern (10). Plant-based diet is beneficial as it is lower in essential amino acids and rich in polyunsaturated fatty acids (11). Weak organic ac...

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    Competing Interests: None declared.
  • Acids and insoluble salts-the balancing act of human cells
    • Qiuyun Liu, Superviser/Writting/Professor, State Key Laboratory of Biocontrol, MOE Key Laboratory of Aquatic Product Safety, Sun Yat-sen University, China
    • Other Contributors:
      • Yunfan Shi, Writting/Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Yulin Wan, Writting/Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Xiaoyi Hu, Writting/Student, Department of Chemical and Biomolecular Engineering, New York University Tandon School of Engineering, USA
      • Zhumei He, Writting/Professor, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Baoyi Liu, Writting/Student, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China
      • Yongchang Cao, Writting/Professor, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China

    Insoluble salts can be formed in human cells, which include salts with organic acids, phosphate, uric acid, cystine, etc., contributing to numerous human diseases. In published Science e-letters (1-2), it was postulated that valine residues possess hyperconjugation and van der Waals interactions between its side group and carbonyl group, thus resulting in strong cation bonding with carbonyl oxygen. This enhances the production of insoluble and rigid salts of organic acids, which may trigger cell death (1). Oxalate analogues could extend lifespans (3-4), perhaps by the inhibition of oxalate generation.
    Hydrogen bond donors and acceptors as well as basic amino acids might help to dissolve insoluble salts. However, the simultaneous presence of high content of hydrogen bond donors and acceptors, and basic amino acids may pose cancer risks (5), due to the local trapping of protons and chloride ions and formation of mutagenic HCl. According to WHO, white meats such as fish diet are safe for consumption, as their proteins may be rich in hydrogen bond donors and acceptors and less rich in basic amino acids. Fish diets are said to be beneficial to cardiovascular disease (6) and perhaps other diseases involving insoluble salts. The hydrogen bond strengths, based on the σ22 element of the 13C chemical shift anisotropy for the deprotonated carboxyl groups of numerous amino acids, are reported in the reference (7). The human long living subpopulation may have stricken a fine bala...

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    Competing Interests: None declared.

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