國立陽明交通大學 生化暨分子生物研究所



職稱 教授
學歷 PhD, Medicinal Chemistry and Pharmaceutics, University of Kentucky, USA
辦公室 生物醫學大樓 六樓 R613 室
電話 886-2-2826-7126
Email alhsu@nycu.edu.tw

中國醫藥大學 研究生事務長


中國醫藥大學 老化醫學研究中心 主任


中國醫藥大學 新藥開發所 教授


國立陽明大學 生化暨分子生物研究所 代理所長


國立陽明大學 生化暨分子生物研究所 教授


美國韋恩州立大學 生命科學系 兼任副教授


美國密西根大學醫學院 分子暨整合生理所 助理教授、終身副教授


美國密西根大學醫學院 內科老年醫學組 助理教授、終身副教授


美國加州大學舊金山分校 生物化學暨生物物理所 博士後研究員

2014, 18

科技部 優秀年輕學者研究計畫補助

2008, 11, 13   

美國國家衛生研究院 科研計畫補助


美國埃里森醫學基金會(Ellison Medical Foundation) 老化年輕學者獎


加拿大國家衛生院 博士後獎學金

Aging is a fundamental process characterized by progressive declines in physiological functions of multiple tissues and an increased likelihood of death. Accumulating evidence suggests that the rate of aging can be controlled by both hormonal and environmental cues. With its short lifespan, extensive genetics and well-described anatomy, the nematode C. elegans has been recognized as an excellent model system for aging studies. The main focus of our laboratory is to understand the biology of aging at the cellular and molecular level by investigating the genetic, environmental, and pharmacological factors that influence the rate of aging and longevity in model organisms. In particular, our current efforts are directed toward the following areas:
(1) Role of HSF-1 in longevity regulation: The importance of protein homeostasis and stress responses in the regulation of longevity and aging has been unveiled by recent studies. Heat-shock transcription factor (HSF-1) is the master regulator of the cellular defense mechanism against heat stress and has recently been directly linked to longevity. Our research has been focus on (i) the cross talks between HSF-1 and insulin/IGF-1 signaling, a well-studied longevity regulatory pathway, (ii) the upstream regulators of HSF-1, and (iii) the downstream targets of HSF-1 that plays important roles in aging regulation.
(2) Role of sirtuins in aging and stress response: Sirtuins are proteins that possess either deacetylase or mono-ribosyltransferase activity. They have been implicated in influencing aging, apoptosis, and stress resistance. We are interested in how SIR-2.4, a worm homolog of human SIRT6, controls stress resistance and aging by modulation the functions of FOXO transcription factor DAF-16.
(3) Genes involved in the longevity response to dietary restriction: Dietary restriction (DR) or caloric restriction (CR) is known to result in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. However, the molecular mechanisms underlying the longevity response of DR remain largely unknown. One of the main focuses of our laboratory is to study genes that mediate this longevity effect of DR. In particular, our current research has been focusing on genes involved in the TOR and AMPK pathway, RNA translation, and SAM-dependent methylation.
(4) Pharmacological intervention that slows aging: The ultimate goal of our research is to develop new therapeutic strategies for combating aging and age-related diseases with the knowledge that we will obtain. We have been actively collaborating with several other groups to identify drugs or nature products that could slow the aging process or delay the onset of age-related neurodegenerative diseases, such as Huntington’s disease.
(5) Functional aging in the nervous system: As animals age, they exhibit a gradual loss in motor activity. We have previously identified the rate of motor activity decline as an excellent longevity predictor in C. elegans. We now aim to investigate the cellular and molecular origin of this age-associated motor activity decline by functionally characterizing the aging nervous system and muscles, in collaboration with a world leading worm electrophysiologist.

Sural S, Liang CY, Wang FY, Ching TT* and Hsu AL*. (2020) HSB-1 signaling regulates longevity by elevating histone H4 levels to control mtDNA transcription. Science Advances,6(43): eaaz4452.


Lombard DB, Kohler W, Guo A, Gendron C, Han M, Ding W, Lyu Y, Ching TT, Wang FY, Chakraborty T, Nikolovska-Coleska Z, Duan Y, Girke T, Hsu AL, Pletcher S, and Miller R. (2020) High throughput small molecule screening reveals NRF2-dependent and -independent pathways of cellular stress resistance Science Advances, 6(40): eaaz7628.


Ching TT, Chen YJ, Li G, Liu J, Xu XZ, and Hsu AL*. (2020) Short-term enhancement of motor neuron synaptic exocytosis during early aging extends lifespan in C. elegans. Experimental Biology and Medicine. 245(17): 1552-1559. doi:10.1177/1535370220950639.


Lin JL, Kuo WL, Huang YH, Jong TL, Hsu AL*, and Hsu WH*. (2020) Using convolutional neural network to measure the physiological age of C. elegans. IEEE/ACM Trans. Comput. Biol. Bioinform. doi: 10.1109/TCBB.2020.2971992. [Epub ahead of print]


Kuo CT, You GT, Jian YJ, Chen TS, Siao YC, Hsu AL, and Ching TT. (2020) AMPK-mediated formation of stress granules is required for dietary restriction-induced longevity in C. elegans. Aging Cell. 19(6): e13157.


Li ST, Zhao HQ, Zhang P, Liang CY, Zhang YP, Hsu AL, and Dong MQ. (2019) DAF-16 stabilizes the aging transcriptome and is activated in mid-aged C. elegans to cope with internal stress. Aging Cell. 18(3): e12896.


Sural S, Lu TC, Jung SA, and Hsu AL*. (2019) HSB-1 inhibition and HSF-1 overexpression triggers overlapping transcriptional changes to promote longevity in C. elegans. G3-Genes Genomes Genetics. 9(5): 1679-1692.


Li G, Gond JK, Liu J, Liu JZ, Li HH, Hsu AL, Liu J, and Xu XZ. (2019) Genetic and pharmacological interventions in the aging motor nervous system slow motor aging and extend lifespan in C. elegans. Science Advances. 5(1): eaau5041.


Son HG, Seo K, Seo M, Park S, Ham S, An SWA, Choi ES, Lee Y, Baek H, Kim E, Ryu Y, Ha CM, Hsu AL, Roh TY, Jang SK, and Lee SJ. (2018) Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C. elegansGenes and Development. 32(23-24): 1562-1575.


Yuan Y, Hakimi P, Kao C, Kao A, Liu R, Janocha A, Boyd-Tesseler A, Hang X, Alhoraibi H, Slate E, Xia K, Cao P, Shue Q, Ching TT, Hsu AL, Erzurum SC, Dubyak GR, Berger NA, Hanson RW, and Feng Z .(2016) Reciprocal changes in phosphoenolpyruvate carboxykinase and pyruvate kinase with age are a determinant of aging in C. elegans. J. Biol. Chem. 291(3):1307-1319


Zhang, B., Xiao, R., Ronan, E.A., He, Y., Hsu, A.L., Liu, J., Xu, X.Z. (2015) Environmental temperature differentially modulates C. elegans longevity through a thermosensitive channel. Cell Reports, 11(9):1414-142.


Huang, C.H., Hsu, F.Y., Wu, Y.H., Zhong, L., Tseng, M.Y., Kuo, C.J., Hsu, A.L.*, Liang, S.S.*, Chiou, S.H.* (2015) Analysis of lifespan-promoting effect of garlic extract by integrated metabolo-proteomics approach. J. Nutritional Biochem. 26(8) 808-817. (*co-corresponding authors)


Vukoti, K., Yu, X., Sheng, Q., Saha, S., Feng, Z., Hsu, A.L.*, and Miyagi, M.* (2015) Monitoriing newly synthesized proteins over the adult life span of C. elegans. J. Proteome Res, 14(3): 1483-94.[Epub: Feb 25, 2015] (*co-corresponding authors)


Horikawa, M., Sural, S., Hsu, A.L., and Antebi, A. (2015) Co-chaperone p23 regulates C. elegans lifespan in response to temperature. PLoS Genetics, 11(4):e1005023.


Kumsta, C., Ching, T.T., Nichimura, M., Davis, A., Gelino, S., Catan, H.H., Panowski, S.H., Baird, N., Chu, C.C., Ong, B., Yu, X., Bodmer, R., Hsu, A.L., Hansen M. (2014) Integrin-linked kinase regulates longevity and thermo-tolerance via neuronal control of HSF-1 in C. elegans. Aging Cell. 13(3): 419-430.


Liu, J., Zhang, B., Lei, H., Feng, Z., Liu, J., Hsu, A.L.., and Xu, X.Z. (2013) Functional aging in the nervous system contributes to age-dependent motor activity decline in C. elegans. Cell Metabolism. 18(3): 392-402.


Chiang, W.C., Tishkoff, D., Yang, B., Wilon-Grady, J., Yu, X., Mazer, T., Eckersdorff, M., Gygi, S., Lombard, D.B., and Hsu, A.L. (2012) C. elegans SIRT6/7 homolog SIR-2.4 promotes DAF-16 localization and function during stress. PLoS Genetics. 8(9): e1002948.


Yuan, Y., Kadiyala, C.S., Ching, T.T., Hakimi, P., Saha, S., Xu, H., Yuan, C., Mullangi, V., Wang, L., Fivenson E., Hanson, R.W., Ewing, R., Hsu, A.L.*, Miyagi, M.*, and Feng, Z.* (2012) Enhanced energy metabolism contributes to the extended lifespan of caloric restricted C. elegans. J Biol Chem. 287(37): 31414-31426. (*co-corresponding authors)


Chiang, W.C, Ching, T.T., Lee, H.C., Mousigian, C., and Hsu, A.L. (2012) HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock response and modulation of longevity. Cell. 148(1-2): 322-334..


Ching, T.T., Chiang, W.C., Chen, C.S., and Hsu, A.L. (2011) Celecoxib extends C. elegans lifespan via inhibition of insulin-like signaling but not cyclooxygenase-2 activity. Aging Cell. 10(3): 506-519.


Ching, T.T. and Hsu, A.L. (2011) Solid plate-based dietary restriction in Caenorhabditis elegans. J Vis Exp. (51): pii: 2701. [Epub: doi: 10.3791/2701].


Ching, T.T., Paal, A., Mehta, A., Zhong, L., and Hsu, A.L. (2010) drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4): 545-557.


Hsu, A.L.*, Feng, Z., Hsieh, M.Y., and Xu, X.Z.* (2009) Identification by machine vision of the rate of motor activity decline as a lifespan predictor in C. elegans. Neurobiology of Aging. 30(9): 1498-1503. (*co-corresponding authors)


Hansen M.*, Hsu, A.L.*, Dillin, A., and Kenyon, C. (2005) New genes tied to endocrine, metabolic and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genetics. 1(1): 119-134. (*co-first authors)


Hsu, A.L., Murphy, C., and Kenyon, C. (2003) Regulation of aging and age-related disease by DAF-16 and Heat-shock factor. Science. 300(5622): 1142-1145.


Dillin, A., Hsu, A.L., Arantes-Oliveira, N., Lehrer-Graiwer, J., Hsin, H., Fraser, A.G., Kamath, R.S., Ahringer, J., and Kenyon, C. (2002) Rates of behavior and aging specified by mitochondrial function during development. Science. 298(5602): 2398-401.


Garigan, D., Hsu, A.L., Fraser, A.G., Kamath, R.S., Ahringer, J., and Kenyon, C. (2002) Genetic analysis of tissue aging in C. elegans: Heat-shock factor prevents progeria and proliferating bacteria kill the animal. Genetics. 161(3): 1101-1112.


Johnson, A.J., Hsu, A.L., Song, X.Q., Lin, H.P., and Chen, C.S. (2002) The cyclooxygenase-2 inhibitor celecoxib perturbs intracellular calcium by inhibiting endoplasmic reticulum Ca2+- ATPases. A plausible link with its anti-tumor effect and cardiovascular Risks. Biochem J. 366(3): 831-837.


Ching, T.T., Hsu, A.L., Johnson, A.J., and Chen, C.S. (2001) Phosphoinositide 3-kinase facilitate antigen-stimulated Ca2+ influx in RBL-2H3 mast cells via a phosphatidylinositol 3,4,5-triphosphate-sensitive Ca2+ entry mechanism. J Biol Chem. 276(18): 14814-14820.


Johnson, A.J., Song, X.Q., Hsu, A.L., and Chen, C.S. (2001) Apoptosis signaling pathway mediated by cyclooxygenase-2 inhibitors in prostate cancer cells. Adv Enzyme Regul. 41: 221-235.


Wang, D.S., Hsu, A.L., and Chen, C.S. (2001) A phosphatidylinositol 3,4,5-triphosphate analogue with low serum-binding affinity. Bioorg Med Chem. 9(1): 133-139.


Hsu, A.L., Ching, T.T., Sen, G., Wang, D.S., Bondada, S., Authi, K.S., and Chen, C.S. (2000) A novel function of phosphoinositide 3-kinase in T-cell calcium signaling: A phosphatidylinositol 3,4,5-triphosphate-mediated Ca2+ entry mechanism. J Biol Chem. 275(21): 16242-16250.


Hsu, A.L., Ching, T.T., Wang, D.S., Song, X.Q., Rangnekar, V.M., and Chen, C.S. (2000) The cyclooxygenase-2 inhibitor celecoxib induces apoptosis by blocking Akt activation in human prostate cancer cells independently of Bcl-2. J Biol Chem. 275(15): 11397-11403.