Current aging research in China

Abstract

The mini-review stemmed from a recent meeting on national aging research strategies in China discusses the components and challenges of aging research in China. Highlighted are the major efforts of a number of research teams, funding situations and outstanding examples of recent major research achievements. Finally, authors discuss potential targets and strategies of aging research in China.

Key words： aging research; funding; objectives and strategies

References

1 Armanios M, Blackburn EH (2012) The telomere syndromes. Nat Rev Genet13: 693-704

2 Bai L, Deng X, Li J, Wang M, Li Q, An W, Deli A, Cong YS (2011) Regulation of cellular senescence by the essential caveolar component PTRF/Cavin-1. Cell Res21: 1088-1101

3 Bayne S, Jones ME, Li H, Pinto AR, Simpson ER, Liu JP (2008) Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice. Cell Res18: 1141-1150

4 Bayne S, Li H, Jones ME, Pinto AR, van Sinderen M, Drummond A, Simpson ER, Liu JP (2011) Estrogen deficiency reversibly induces telomere shortening in mouse granulosa cells and ovarian aging in vivo. Protein Cell2: 333-346

5 Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L (2010) Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab11: 35-46

6 Blagosklonny MV (2012) Answering the ultimate question “what is the proximal cause of aging?”. Aging (Albany NY)4: 861-877

7 Cao Y, Li H, Mu F-T, Ebisui O, Funder JW, Liu JP (2002) Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. FASEB J16: 96-98

8 Cassar L, Li H, Pinto AR, Nicholls C, Bayne S, Liu JP (2008) Bone morphogenetic protein-7 inhibits telomerase activity, telomere maintenance, and cervical tumor growth. Cancer Res68: 9157-9166

9 Chen LY, Zhang Y, Zhang Q, Li H, Luo Z, Fang H, Kim SH, Qin L, Yotnda P, Xu J (2012) Mitochondrial localization of telomeric protein TIN2 links telomere regulation to metabolic control. Mol Cell47: 839-850

10 Chen Y, Ma X, Zhang M, Wang X, Wang C, Wang H, Guo P, Yuan W, Rudolph KL, Zhan Q (2014) Gadd45a regulates hematopoietic stem cell stress responses in mice. Blood123: 851-862

11 Christensen K, Doblhammer G, Rau R, Vaupel JW (2009) Ageing populations: the challenges ahead. Lancet374: 1196-1208

12 Cong YS, Wen J, Bacchetti S (1999) The human telomerase catalytic subunit hTERT: organization of the gene and characterization of the promoter. Hum Mol Genet8: 137-142

13 Ding D, Xi P, Zhou J, Wang M, Cong YS (2013) Human telomerase reverse transcriptase regulates MMP expression independently of telomerase activity via NF-kappaB-dependent transcription. FASEB J27: 4375-4383

14 Eisenberg T, Knauer H, Schauer A, Buttner S, Ruckenstuhl C, Carmona-Gutierrez D, Ring J, Schroeder S, Magnes C, Antonacci L (2009) Induction of autophagy by spermidine promotes longevity. Nat Cell Biol11: 1305-1314

15 Feng J, Zhang J, Liu M, Wan G, Qi K, Zheng C, Lv Z, Hu C, Zeng Y, Gregory SG (2011) Association of mtDNA haplogroup F with healthy longevity in the female Chuang population, China. Exp Gerontol46: 987-993

16 Green DR, Galluzzi L, Kroemer G (2011) Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science333: 1109-1112

17 Han Y, Han D, Yan Z, Boyd-Kirkup JD, Green CD, Khaitovich P, Han JD (2012) Stress-associated H3K4 methylation accumulates during postnatal development and aging of rhesus macaque brain. Aging Cell11: 1055-1064

18 Han X, Liu D, Zhang Y, Li Y, Lu W, Chen J, Songyang Z (2013) Akt regulates TPP1 homodimerization and telomere protection. Aging Cell12: 1091-1099

19 Hayflick L (2007) Biological aging is no longer an unsolved problem. Ann NY Acad Sci1100: 1-13

20 Jin C, Li J, Green CD, Yu X, Tang X, Han D, Xian B, Wang D, Huang X, Cao X (2011) Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell Metab14: 161-172

21 Ju Z, Jiang H, Jaworski M, Rathinam C, Gompf A, Klein C, Trumpp A, Lenhard Rudolph K (2007) Telomere dysfunction induces environmental alterations limiting hematopoietic stem cell function and engraftment. Nat Med13: 742-747

22 Kirkwood TB (2008) A systematic look at an old problem. Nature451: 644-647

23 Krishnan V, Chow MZ, Wang Z, Zhang L, Liu B, Liu X, Zhou Z (2011) Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice. Proc Natl Acad Sci USA108: 12325-12330

24 Kruegel U, Robison B, Dange T, Kahlert G, Delaney JR, Kotireddy S, Tsuchiya M, Tsuchiyama S, Murakami CJ, Schleit J (2011) Elevated proteasome capacity extends replicative lifespan in Saccharomyces cerevisiae. PLoS Genet7: e1002253

25 Le R, Kou Z, Jiang Y, Li M, Huang B, Liu W, Li H, Kou X, He W, Rudolph KL (2014) Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced pluripotent stem cells. Cell Stem Cell14: 27-39

26 Li Y, Wang WJ, Cao H, Lu J, Wu C, Hu FY, Guo J, Zhao L, Yang F, Zhang YX (2009) Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet18: 4897-4904

27 Li Q, Zhang Y, Fu J, Han L, Xue L, Lv C, Wang P, Li G, Tong T (2013) FOXA1 mediates p16(INK4a) activation during cellular senescence. EMBO J32: 858-873

28 Liu JP (2014) Molecular mechanisms of ageing and related diseases. Clin Exp Pharmacol Physiol41: 445-458

29 Liu D, Safari A, O’Connor MS, Chan DW, Laegeler A, Qin J, Songyang Z (2004) PTOP interacts with POT1 and regulates its localization to telomeres. Nat Cell Biol6: 673-680

30 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 Med11: 780-785

31 Liu F, Wu S, Ren H, Gu J (2011a) Klotho suppresses RIG-I-mediated senescence-associated inflammation. Nat Cell Biol13: 254-262

32 Liu G, Rogers J, Murphy CT, Rongo C (2011b) EGF signalling activates the ubiquitin proteasome system to modulate C. elegans lifespan. EMBO J30: 2990-3003

33 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 Metab16: 738-750

34 Liu GH, Ding Z, Izpisua Belmonte JC (2012b) iPSC technology to study human aging and aging-related disorders. Curr Opin Cell Biol24: 765-774

35 Liu B, Wang Z, Zhang L, Ghosh S, Zheng H, Zhou Z (2013) Depleting the methyltransferase Suv39h1 improves DNA repair and extends lifespan in a progeria mouse model. Nat Commun4: 1868

36 Liu M, Bai J, He S, Villarreal R, Hu D, Zhang C, Yang X, Liang H, Slaga TJ, Yu Y (2014) Grb10 promotes lipolysis and thermogenesis by phosphorylation-dependent feedback inhibition of mTORC1. Cell Metab19: 967-980

37 Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging.Cell153: 1194-1217

38 Lu X, Li X, He Q, Gao J, Gao Y, Liu B, Liu F (2013) miR-142-3p regulates the formation and differentiation of hematopoietic stem cells in vertebrates. Cell Res23: 1356-1368

39 Nicholls C, Pinto AR, Li H, Li L, Wang L, Simpson R, Liu JP(2012) Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component. Proc Natl Acad Sci USA109: 13308-13313

40 O’Connor MS, Safari A, Xin H, Liu D, Songyang Z (2006) A critical role for TPP1 and TIN2 interaction in high-order telomeric complex assembly. Proc Natl Acad Sci USA103: 11874-11879

41 Rubinsztein DC, Marino G, Kroemer G (2011) Autophagy and aging. Cell146: 682-695

42 Shao M, Shan B, Liu Y, Deng Y, Yan C, Wu Y, Mao T, Qiu Y, Zhou Y, Jiang S (2014) Hepatic IRE1alpha regulates fasting-induced metabolic adaptive programs through the XBP1 s-PPARalpha axis signalling. Nat Commun5: 3528

43 Song W, Ren D, Li W, Jiang L, Cho KW, Huang P, Fan C, Song Y, Liu Y, Rui L (2010) SH2B regulation of growth, metabolism, and longevity in both insects and mammals. Cell Metab11: 427-437

44 Spong A, Bartke A (2012) Rapamycin slows aging in mice. Cell Cycle11: 845

45 Sun L, Hu CY, Shi XH, Zheng CG, Huang ZZ, Lv ZP, Huang J, Wan G, Qi KY, Liang SY (2013) Trans-ethnical shift of the risk genotype in the CETP I405 V with longevity: a Chinese casecontrol study and meta-analysis. PLoS ONE8: e72537

46 Sun L, Hu C, Zheng C, Huang Z, Lv Z, Huang J, Liang S, Shi X, Zhu X, Yuan H (2014) Gene-gene interaction between CETP and APOE polymorphisms confers higher risk for hypertriglyceridemia in oldest-old Chinese women. Exp Gerontol55: 129-133

47 Tomaru U, Takahashi S, Ishizu A, Miyatake Y, Gohda A, Suzuki S, Ono A, Ohara J, Baba T, Murata S (2012) Decreased proteasomal activity causes age-related phenotypes and promotes the development of metabolic abnormalities. Am J Pathol180: 963-972

48 Vendelbo MH, Nair KS (2011) Mitochondrial longevity pathways. Biochim Biophys Acta1813: 634-644

49 Wang F, Tang ML, Zeng ZX, Wu RY, Xue Y, Hao YH, Pang DW, Zhao Y, Tan Z (2012a) Telomere- and telomerase-interacting protein that unfolds telomere G-quadruplex and promotes telomere extension in mammalian cells. Proc Natl Acad Sci USA109: 20413-20418

50 Wang F, Yin Y, Ye X, Liu K, Zhu H, Wang L, Chiourea M, Okuka M, Ji G, Dan J (2012b) Molecular insights into the heterogeneity of telomere reprogramming in induced pluripotent stem cells. Cell Res22: 757-768

51 Wang X, Huang T, Bu G, Xu H (2014) Dysregulation of protein trafficking in neurodegeneration. Mol Neurodegener9: 31

52 Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, Hejtmancik JF, Nadon N, Strong R, Wood LK (2012) Rapamycin slows aging in mice. Aging Cell11: 675-682

53 Wolff S, Dillin A (2013) Ageing: beneficial miscommunication. Nature497: 442-443

54 Wu K, Ren R, Su W, Wen B, Zhang Y, Yi F, Qiao X, Yuan T, Wang J, Liu L (2014) A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation. J Biol Chem289: 20193-20199

55 Xie Q, Chen J, Feng H, Peng S, Adams U, Bai Y, Huang L, Li J, Huang J, Meng S (2013) YAP/TEAD-mediated transcription controls cellular senescence. Cancer Res73: 3615-3624

56 Xin H, Liu D, Wan M, Safari A, Kim H, Sun W, O’Connor MS, Songyang Z (2007) TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature445: 559-562

57 Xu D, Dwyer J, Li H, Duan W, Liu JP (2008) Ets2 maintains hTERT gene expression and breast cancer cell proliferation by interacting with c-Myc. J Biol Chem283: 23567-23580

58 Xu F, Pang L, Cai X, Liu X, Yuan S, Fan X, Jiang B, Zhang X, Dou Y, Gorospe M (2014) let-7-repressesed Shc translation delays replicative senescence. Aging Cell13: 185-192

59 Yang P, Zhang H (2014) You are what you eat: multifaceted functions of autophagy during C. elegans development. Cell Res24: 80-91

60 Yang Z, Huang X, Jiang H, Zhang Y, Liu H, Qin C, Eisner GM, Jose PA, Rudolph L, Ju Z (2009) Short telomeres and prognosis of hypertension in a chinese population. Hypertension53: 639-645

61 Zhang J, Zhang N, Liu M, Li X, Zhou L, Huang W, Xu Z, Liu J, Musi N, DeFronzo RA (2012a) Disruption of growth factor receptor-binding protein 10 in the pancreas enhances beta-cell proliferation and protects mice from streptozotocin-induced betacell apoptosis. Diabetes61: 3189-3198

62 Zhang X, Liu Z, Yi J, Tang H, Xing J, Yu M, Tong T, Shang Y, Gorospe M, Wang W (2012b) The tRNA methyltransferase NSun2 stabilizes p16INK(4) mRNA by methylating the 3′-untranslated region of p16. Nat Commun3: 712

63 Zhang Y, Chen LY, Han X, Xie W, Kim H, Yang D, Liu D, Songyang Z (2013) Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment. Proc Natl Acad Sci USA110: 5457-5462

64 Zhang L, Sun Y, Fei M, Tan C, Wu J, Zheng J, Tang J, Sun W, Lv Z, Bao J (2014) Disruption of chaperone-mediated autophagydependent degradation of MEF2A by oxidative stress-induced lysosome destabilization. Autophagy10: 1015-1035

65 Zhou B, Yang L, Li S, Huang J, Chen H, Hou L, Wang J, Green CD, Yan Z, Huang X (2012) Midlife gene expressions identify modulators of aging through dietary interventions. Proc Natl Acad Sci USA109: E1201-E1209

66 Zhou J, Mao B, Zhou Q, Ding D, Wang M, Guo P, Gao Y, Shay JW, Yuan Z, Cong YS (2014) Endoplasmic reticulum stress activates telomerase. Aging Cell13: 197-200

67 Zhu X, Wang F, Zhao Y, Yang P, Chen J, Sun H, Liu L, Li W, Pan L, Guo Y (2014) A Gain-of-Function Mutation in Tnni2 Impeded Bone Development through Increasing Hif3a Expression in DA2B Mice. PLoS Genet10: e1004589

68 Zuo B, Yang J, Wang F, Wang L, Yin Y, Dan J, Liu N, Liu L (2012) Influences of lamin A levels on induction of pluripotent stem cells. Biol Open1: 1118-1127