PERSPECTIVE

Basic and translational aging research in China: present and future

  • Xiaojuan He 1,2 ,
  • Moshi Song 3,4,5 ,
  • Jing Qu 4,5,6 ,
  • Yansu Guo 7 ,
  • Heqi Cao 7 ,
  • Ruijuan Sun , 7 ,
  • Guang-Hui Liu , 1,2,4,5 ,
  • Yong Shen , 8 ,
  • Major Program Expert Group 7
Expand
  • 1. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
  • 2. National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
  • 3. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
  • 4. University of Chinese Academy of Sciences, Beijing 100049, China
  • 5. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
  • 6. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
  • 7. Department of Health Sciences, National Natural Science Foundation of China, Beijing 100085, China
  • 8. University of Science and Technology of China, Hefei 230027, China

Published date: 15 Jul 2019

Copyright

2019 The Author(s) 2019

Cite this article

Xiaojuan He , Moshi Song , Jing Qu , Yansu Guo , Heqi Cao , Ruijuan Sun , Guang-Hui Liu , Yong Shen , Major Program Expert Group . Basic and translational aging research in China: present and future[J]. Protein & Cell, 2019 , 10(7) : 476 -484 . DOI: 10.1007/s13238-019-0617-0

1
Adli M (2018) The CRISPR tool kit for genome editing and beyond. Nat Commun 9(1):1911

DOI

2
Awan HM, Shah A, Rashid F, Shan G(2017) Primate-specific Long Non-coding RNAs and MicroRNAs. Genomics Proteomics Bioinforma 15(3):187–195

DOI

3
Bao S, Tang F, Li X, Hayashi K, Gillich A, Lao K, Surani MA (2009) Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells. Nature 461(7268):1292–1295

DOI

4
Campisi J (2005) Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors. Cell 120(4):513–522

DOI

5
Chen W, Qian W, Wu G, Chen W, Xian B, Chen X, Cao Y, Green CD, Zhao F, Tang K (2015) Three-dimensional human facial morphologies as robust aging markers. Cell Res 25(5):574–587

DOI

6
Chen Y, Li Y, Peng Y, Zheng X, Fan S, Yi Y, Zeng P, Chen H, Kang H, Zhang Y (2018) ΔNp63α down-regulates c-Myc modulator MM1 via E3 ligase HERC3 in the regulation of cell senescence. Cell Death Differ 25(12):2118–2129

DOI

7
Cheng X, He P, Lee T, Yao H, Li R, Shen Y (2014) High activities of BACE1 in Brains with mild cognitive impairment. Am J Pathol 184(1):141–147

DOI

8
Cheng H, Xuan H, Green CD, Han Y, Sun N, Shen H, McDermott J, Bennett DA, Lan F, Han J-DJ (2018) Repression of human and mouse brain inflammaging transcriptome by broad gene-body histone hyperacetylation. Proc Natl Acad Sci 115(29):7611–7616

DOI

9
Davie K, Janssens J, Koldere D, De Waegeneer M, Pech U, Kreft Ł, Aibar S, Makhzami S, Christiaens V, Bravo González-Blas C (2018) A single-cell transcriptome atlas of the aging drosophila brain. Cell 174(4):982–998

DOI

10
Deng T, Huang Y, Weng K, Lin S, Li Y, Shi G, Chen Y, Huang J, Liu D, Ma W (2018) TOE1 acts as a 3’ exonuclease for telomerase RNA and regulates telomere maintenance. Nucleic Acids Res 47(1):391–405

DOI

11
Duan J, Zhang Z, Tong T (2001) Senescence delay of human diploid fibroblast induced by anti-sense p16INK4a expression. J Biol Chem 276(51):48325–48331

DOI

12
Enge M, Arda HE, Mignardi M, Beausang J, Bottino R, Kim SK, Quake SR (2017) Single-cell analysis of human pancreas reveals transcriptional signatures of aging and somatic mutation patterns. Cell 171(2):321–330

DOI

13
Fatehullah A, Tan SH, Barker N (2016) Organoids as an in vitro model of human development and disease. Nat Cell Biol 18(3):246–254

DOI

14
Franceschi C, Campisi J (2014) Chronic inflammation (Inflammaging) and its potential contribution to age-associated diseases. J Gerontol Ser A Biol Sci Med Sci 69(1):S4–S9

DOI

15
Fu L, Xu X, Ren R, Wu J, Zhang W, Yang J, Ren X, Wang S, Zhao Y, Sun L (2016) Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs. Protein Cell 7(3):210–221

DOI

16
Gan W, Liu XL, Yu T, Zou YG, Li TT, Wang S, Deng J, Wang LL, Cai JP (2018) Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker of aging. Front Aging Neurosci 10:34

DOI

17
Gao F, Li G, Liu C, Gao H, Wang H, Liu W, Chen M, Shang Y, Wang L, Shi J (2018a) Autophagy regulates testosterone synthesis by facilitating cholesterol uptake in Leydig cells. J Cell Biol 217(6):2103–2119

DOI

18
Gao J, Feng Z, Wang X, Zeng M, Liu J, Han S, Xu J, Chen L, Cao K, Long J (2018b) SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress. Cell Death Differ 25(2):229–240

DOI

19
Geng L, Liu Z, Zhang W, Li W, Wu Z, Wang W, Ren R, Su Y, Wang P, Sun L (2018) Chemical screen identifies a geroprotective role of quercetin in premature aging. Protein Cell. https://doi.org/10.1007/s13238-018-0567-y

DOI

20
Guo Y, Nie Q, MacLean AL, Li Y, Lei J, Li S (2017) Multiscale modeling of inflammation-induced tumorigenesis reveals competing oncogenic and oncoprotective roles for inflammation. Cancer Res 77(22):6429–6441

DOI

21
Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, Walker AJ, Gergits F, Segel M, Nemesh J (2018) Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 50(1):253–271

DOI

22
Han X, Wang R, Zhou Y, Fei L, Sun H, Lai S, Saadatpour A, Zhou Z, Chen H, Ye F (2018) Mapping the mouse cell atlas by microwell-seq. Cell 173(5):1307

DOI

23
Kirkwood TBL (2005) Understanding the odd science of aging. Cell 120(4):437–447

DOI

24
Kubben N, Zhang W, Wang L, Voss TC, Yang J, Qu J, Liu GH, Misteli T (2016) Repression of the antioxidant NRF2 pathway in premature aging. Cell 165(6):1361–1374

DOI

25
Kudlow BA, Kennedy BK, Monnat RJ (2007) Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human progeroid diseases. Nat Rev Mol Cell Biol 8(5):394–404

DOI

26
Li F, Kim H, Ji Z, Zhang T, Chen B, Ge Y, Hu Y, Feng X, Han X, Xu H (2018) The BUB3-BUB1 complex promotes telomere DNA replication. Mol Cell 70(3):395–407

DOI

27
Liao S, Dong W, Lv L, Guo H, Yang J, Zhao H, Huang R, Yuan Z, Chen Y, Feng S (2017) Heart regeneration in adult Xenopus tropicalis after apical resection. Cell Biosci 7:70

DOI

28
Ling C, Liu Z, Song M, Zhang W, Wang S, Liu X (2019) Modeling CADASIL vascular pathologies with patient-derived induced pluripotent stem cells. Protein Cell 10(4):249–271

DOI

29
Liu B, Wang J, Chan KM, Tjia WM, Deng W, Guan X, Huang JD, Li KM, Chau PY, Chen DJ (2005) Genomic instability in laminopathy-based premature aging. Nat Med 11(7):780–785

DOI

30
Liu GH, Barkho BZ, Ruiz S, Diep D, Qu J, Yang SL, Panopoulos AD, Suzuki K, Kurian L, Walsh C (2011a) Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome. Nature 472(7342):221–225

DOI

31
Liu GH, Suzuki K, Qu J, Sancho-Martinez I, Yi F, Li M, Kumar S, Nivet E, Kim J, Soligalla RD (2011b) Targeted gene correction of laminopathy-associated LMNA mutations in patientspecific iPSCs. Cell Stem Cell 8(6):688–694

DOI

32
Liu B, Ghosh S, Yang X, Zheng H, Liu X, Wang Z, Jin G, Zheng B, Kennedy BK, Suh Y (2012a) Resveratrol rescues SIRT1-dependent adult stem cell decline and alleviates progeroid features in laminopathy-based progeria. Cell Metab 16(6):738–750

DOI

33
Liu GH, Qu J, Suzuki K, Nivet E, Li M, Montserrat N, Yi F, Xu X, Ruiz S, Zhang W (2012b) Progressive degeneration of human neural stem cells caused by pathogenic LRRK2. Nature 491(7425):603–607

DOI

34
Liu GH, Suzuki K, Li M, Qu J, Montserrat N, Tarantino C, Gu Y, Yi F, Xu X, Zhang W (2014a) Modelling Fanconi anemia pathogenesis and therapeutics using integration-free patientderived iPSCs. Nat Commun 5:4330

DOI

35
Liu M, Bai J, He S, Villarreal R, Hu D, Zhang C, Yang X, Liang H, Slaga TJ, Yu Y (2014b) Grb10 promotes lipolysis and thermogenesis by phosphorylation-dependent feedback inhibition of mTORC1. Cell Metab 19(6):967–980

DOI

36
Liu S, Zhang Y, Wang X, Wang Z, Chen D, Zhang B, Tian RR, Wu J, Zhang Y, Xu K (2017) Annotation and cluster analysis of spatiotemporaland sex-related lncRNA expression in rhesus macaque brain. Genome Res 27(9):1608–1620

DOI

37
Liu H, Zhang H, Wu X, Ma D, Wu J, Wang L, Jiang Y, Fei Y, Zhu C, Tan R (2018a) Nuclear cGAS suppresses DNA repair and promotes tumorigenesis. Nature 563(7729):131–136

DOI

38
Liu Y, Liu F, Cao Y, Xu H, Wu Y, Wu S, Liu D, Zhao Y, Songyang Z, Ma W (2018b) Shwachman-diamond syndrome protein SBDS maintains human telomeres by regulating telomerase recruitment. Cell Rep 22(7):1849–1860

DOI

39
López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217

DOI

40
López-Otín C, Galluzzi L, Freije JMP, Madeo F, Kroemer G (2016) Metabolic control of longevity. Cell 166(4):802–821

DOI

41
Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM (2015) Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161(5):1202–1214

DOI

42
Mao C-Z, Zheng L, Zhou Y-M, Wu H-Y, Xia J-B, Liang C-Q, Guo X-F, Peng W-T, Zhao H, Cai W-B (2018) CRISPR/Cas9-mediated efficient and precise targeted integration of donor DNA harboring double cleavage sites in Xenopus tropicalis. FASEB J 32(12):6495–6509

DOI

43
Mendez-Bermudez A, Lototska L, Bauwens S, Giraud-Panis MJ, Croce O, Jamet K, Irizar A, Mowinckel M, Koundrioukoff S, Nottet N (2018) Genome-wide control of heterochromatin replication by the telomere capping protein TRF2. Mol Cell 70(3):449–461

DOI

44
Nelson EE, Winslow JT (2009) Non-human primates: Model animals for developmental psychopathology. Neuropsychopharmacology 34(1):90–105

DOI

45
Pan H, Guan D, Liu X, Li J, Wang L, Wu J, Zhou J, Zhang W, Ren R, Zhang W (2016) SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2. Cell Res 26(2):190–205

DOI

46
Pas SP (2018) The rise of three-dimensional human brain cultures. Nature 553(7689):437–445

DOI

47
Phillips KA, Bales KL, Capitanio JP, Conley A, Czoty PW, ’t Hart BA, Hopkins WD, Hu SL, Miller LA, Nader MA (2014) Why primate models matter. Am J Primatol 76(9):801–827

DOI

48
Quadrato G, Brown J, Arlotta P (2016) The promises and challenges of human brain organoids as models of neuropsychiatric disease. Nat Med 22(11):1220–1228

DOI

49
Sebastiani P, Solovieff N, DeWan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB (2012) Genetic signatures of exceptional longevity in humans. PLoS One 7(1):e29848

DOI

50
Sen P, Shah PP, Nativio R, Berger SL (2016) Epigenetic mechanisms of longevity and aging. Cell 166(4):822–839

DOI

51
Shekhar K, Lapan SW, Whitney IE, Tran NM, Macosko EZ, Kowalczyk M, Adiconis X, Levin JZ, Nemesh J, Goldman M (2016) Comprehensive classification of retinal bipolar neurons by single-cell transcriptomics. Cell 166(5):1308–1323

DOI

52
Shen EZ, Song CQ, Lin Y, Zhang WH, Su PF, Liu WY, Zhang P, Xu J, Lin N, Zhan C (2014) Mitoflash frequency in early adulthood predicts lifespan in caenorhabditis elegans. Nature 508(7494):128–132

DOI

53
Spanjaard B, Hu B, Mitic N, Olivares-Chauvet P, Janjuha S, Ninov N, Junker JP (2018) Simultaneous lineage tracing and cell-type identification using CrIsPr-Cas9-induced genetic scars. Nat Biotechnol 36(5):469–473

DOI

54
Tang F, Barbacioru C, Wang Y, Nordman E, Lee C, Xu N, Wang X, Bodeau J, Tuch BB, Siddiqui A (2009) mRNA-Seq wholetranscriptome analysis of a single cell. Nat Methods 6(5):377–382

DOI

55
Tang F, Barbacioru C, Bao S, Lee C, Nordman E, Wang X, Lao K, Surani MA (2010) Tracing the derivation of embryonic stem cells from the inner cell mass by single-cell RNA-seq analysis. Cell Stem Cell 6(5):468–478

DOI

56
Tang H, Wang H, Cheng X, Fan X, Yang F, Zhang M, Chen Y, Tian Y, Liu C, Shao D (2018) HuR regulates telomerase activity through TERC methylation. Nat Commun 9(1):2213

DOI

57
Tao R, Zhao Y, Chu H, Wang A, Zhu J, Chen X, Zou Y, Shi M, Liu R, Su N (2017) Genetically encoded fluorescent sensors reveal dynamic regulation of NADPH metabolism. Nat Methods 14(7):720–728

DOI

58
Vallender EJ, Miller GM (2013) Nonhuman primate models in the genomic era: a paradigm shift. ILAR J 54(2):154–165

DOI

59
Wang W, Wu J, Zhang Z, Tong T (2001) Characterization of regulatory elements on the promoter region of p16INK4a that contribute to overexpression of p16 in senescent fibroblasts. J Biol Chem 276(52):48655–48661

DOI

60
Wang H, Diao D, Shi Z, Zhu X, Gao Y, Gao S, Liu X, Wu Y, Rudolph KL, Liu G (2016a) SIRT6 controls hematopoietic stem cell homeostasis through epigenetic regulation of Wnt signaling. Cell Stem Cell 18(4):495–507

DOI

61
Wang H, La Russa M, Qi LS (2016b) CRISPR/Cas9 in genome editing and beyond. Annu Rev Biochem 85:227–264

DOI

62
Wang S, Wang L, Dou L, Guo J, Fang W, Li M, Meng X, Man Y, Shen T, Huang X (2016c) MicroRNA 152 regulates hepatic glycogenesis by targeting PTEN. FEBS J 283(10):1935–1946

DOI

63
Wang L, Yi F, Fu L, Yang J, Wang S, Wang Z, Suzuki K, Sun L, Xu X, Yu Y (2017) CRISPR/Cas9-mediated targeted gene correction in amyotrophic lateral sclerosis patient iPSCs. Protein Cell 8(5):365–378

DOI

64
Wang H, Zuo H, Liu J, Wen F, Gao Y, Zhu X, Liu B, Xiao F, Wang W, Huang G (2018a) Loss of YTHDF2-mediated m6A-dependent mRNA clearance facilitates hematopoietic stem cell regeneration. Cell Res 28(10):1035–1038

DOI

65
Wang XF, Chen XQ, Yu Q, Liu YW, Yang LQ, He YH, Kong QP, Kong QP (2018b) Transcriptome evidence reveals enhanced autophagy-lysosomal function in centenarians. Genome Res 28(11):1601–1610

DOI

66
Wimmer RA, Leopoldi A, Aichinger M, Wick N, Hantusch B, Novatchkova M, Taubenschmid J, Hämmerle M, Esk C, Bagley JA (2019) Human blood vessel organoids as a model of diabetic vasculopathy. Nature 565(7740):505–510

DOI

67
Wu Z, Zhang W, Song M, Wang W, Wei G, Li W, Lei J, Huang Y, Sang Y, Chan P (2018) Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome. Protein Cell 9(4):333–350

DOI

68
Xie HF, Liu YZ, Du R, Wang B, Chen MT, Zhang YY, Deng HL, Li J (2017) Mir-377 induces senescence in human skin fibroblasts by targeting DNA methyltransferase 1. Cell Death Dis 8(3):e2663

DOI

69
Xu C, Ai D, Suo S, Chen X, Yan Y, Cao Y, Sun N, Chen W, McDermott J, Zhang S (2018a) Accurate drug repositioning through non-tissue-specific core signatures from cancer transcriptomes. Cell Rep 25(2):523–535

DOI

70
Xu D, Jin T, Zhu H, Chen H, Ofengeim D, Zou C, Mifflin L, Pan L, Amin P, Li W (2018b) TBK1 suppresses RIPK1-driven apoptosis and inflammation during development and in aging. Cell 174(6):1477–1491

DOI

71
Xu S, Liu P, Chen Y, Chen Y, Zhang W, Zhao H, Cao Y, Wang F, Jiang N, Lin S (2018c) Foxp2 regulates anatomical features that may be relevant for vocal behaviors and bipedal locomotion. Proc Natl Acad Sci 115(35):8799–8804

DOI

72
Yan S, Tu Z, Liu Z, Fan N, Yang H, Yang S, Yang W, Zhao Y, Ouyang Z, Lai C (2018) A huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington’s disease. Cell 173(4):989–1002

DOI

73
Yan P, Li Q, Wang L, Lu P, Suzuki K, Liu Z, Lei J, Li W (2019) FOXO3-engineered human ESC-derived vascular cells promote vascular protection and regeneration. Stem Cell 24(3):447–461

DOI

74
Yang G, Lu X, Yuan L (2014) LncRNA: a link between RNA and cancer. Biochim Biophys Acta Gene Regul Mech 1839(11):1097–1109

DOI

75
Yang J, Li J, Suzuki K, Liu X, Wu J, Zhang W, Ren R, Zhang W, Chan P, Izpisua Belmonte JC (2017) Genetic enhancement in cultured human adult stem cells conferred by a single nucleotide recoding. Cell Res 27(9):1178–1181

DOI

76
Yi Y, Xie H, Xiao X, Wang B, Du R, Liu Y, Li Z, Wang J, Sun L, Deng Z (2018) Ultraviolet a irradiation induces senescence in human dermal fibroblasts by down-regulating DNMT1 via ZEB1. Aging (Albany NY) 10(2):212–228

DOI

77
Yu C, Qu J, Yao X, Li Y, Suzuki K, Benner C, Yuan T, Goebl A, Kim NY, Izpisua Belmonte JC (2014) Targeted gene correction minimally impacts whole-genome mutational load in humandisease-specific induced pluripotent stem cell clones. Cell Stem Cell 15(1):31–36

DOI

78
Yu M, Fu Y, Liang Y, Song H, Yao Y, Wu P, Yao Y, Pan Y, Wen X, Ma L (2017) Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington’s disease models. Cell Res 27(12):1441–1465

DOI

79
Zeng Z, Zhang Z, Yu H, Corbley MJ, Tang Z, Tong T (1999) Mitochondrial DNA deletions are associated with ischemia and aging in Balb/c mouse brain. J Cell Biochem 73(4):545–553

DOI

80
Zeng Y, Nie C, Min J, Liu X, Li M, Chen H, Xu H, Wang M, Ni T, Li Y (2016) Novel loci and pathways significantly associated with longevity. Sci Rep 6:21243

DOI

81
Zhang X, Chen Z, Chen Y, Tong T (2003) Delivering antisense telomerase RNA by a hybrid adenovirus/adeno-associated virus significantly suppresses the malignant phenotype and enhances cell apoptosis of human breast cancer cells. Oncogene 22(16):2405–2416

DOI

82
Zhang W, Li J, Suzuki K, Qu J, Wang P, Zhou J, Liu X, Ren R, Xu X, Ocampo A (2015) A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging. Science 348(6239):1160–1163

DOI

83
Zhang W, Song M, Qu J, Liu GH (2018a) Epigenetic modifications in cardiovascular aging and diseases. Circ Res 123(7):773–786

DOI

84
Zhang W, Wan H, Feng G, Qu J, Wang J, Jing Y, Ren R, Liu Z, Zhang L, Chen Z (2018b) SIRT6 deficiency results in developmental retardation in cynomolgus monkeys. Nature 560 (7720):661–665

DOI

85
Zhu H, Zou G, Wang N, Zhuang M, Xiong W, Huang G (2017) Single-neuron identification of chemical constituents, physiological changes, and metabolism using mass spectrometry. Proc Natl Acad Sci 114(10):2586–2591

DOI

86
Zou Y, Wang A, Shi M, Chen X, Liu R, Li T, Zhang C, Zhang Z, Zhu L, Ju Z (2018) Analysis of redox landscapes and dynamics in living cells and in vivo using genetically encoded fluorescent sensors. Nat Protoc 13(10):2362–2386

DOI

Outlines

/