Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses

IL-17 and th17 cells

Korn, T., Bettelli, E., Oukka, M., & Kuchroo, V. K. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132710 · Cited by 4,873

Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase

Yamauchi, T., Kamon, J., Minokoshi, Y., Ito, Y., Waki, H., Uchida, S., Yamashita, S., Noda, M., Kita, S., Ueki, K., et al. (2002) · Nature Medicine · doi:10.1038/nm788 · Cited by 4,238

A central role for JNK in obesity and insulin resistance

Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359

Obesity and insulin resistance

Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,345

AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity

Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300

Extending Healthy Life Span—From Yeast to Humans

Fontana, L., Partridge, L., & Longo, V. D. (2010) · Science · doi:10.1126/science.1172539 · Cited by 3,023

The AMPK signalling pathway coordinates cell growth, autophagy and metabolism

Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923

The integrated stress response

Pakos‐Zebrucka, K., Koryga, I., Mnich, K., Ljujic, M., Samali, A., & Gorman, A. M. (2016) · The EMBO Reports · doi:10.15252/embr.201642195 · Cited by 2,659

Brown and beige fat: Development, function and therapeutic potential

Harms, M., & Seale, P. (2013) · Nature Medicine · doi:10.1038/nm.3361 · Cited by 2,328

Autophagy and Aging

Rubinsztein, D. C., Mariño, G., & Kroemer, G. (2011) · Cell · doi:10.1016/j.cell.2011.07.030 · Cited by 2,107

Sirtuins as regulators of metabolism and healthspan

Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008

mTOR is a key modulator of ageing and age-related disease

Johnson, S. C., Rabinovitch, P. S., & Kaeberlein, M. (2013) · Nature · doi:10.1038/nature11861 · Cited by 1,676

A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy

Lee, I. H., Cao, L., Mostoslavsky, R., Lombard, D. B., Liu, J., Bruns, N. E., Tsokos, M., Alt, F. W., & Finkel, T. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712145105 · Cited by 1,510

Endocrine Regulation of the Fasting Response by PPARα-Mediated Induction of Fibroblast Growth Factor 21

Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504

Hepatic Fibroblast Growth Factor 21 Is Regulated by PPARα and Is a Key Mediator of Hepatic Lipid Metabolism in Ketotic States

Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495

FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis

Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478

The mitochondrial basis of aging

Sun, N., Youle, R. J., & Finkel, T. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.01.028 · Cited by 1,441

miR-34a repression of SIRT1 regulates apoptosis

Yamakuchi, M., Ferlito, M., & Lowenstein, C. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801613105 · Cited by 1,362

Genetic pathways that regulate ageing in model organisms

Guarente, L., & Kenyon, C. J. (2000) · Nature · doi:10.1038/35041700 · Cited by 1,337

Adipose tissue browning and metabolic health

Bartelt, A., & Heeren, J. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.204 · Cited by 1,177

The eIF2α/ATF4 pathway is essential for stress-induced autophagy gene expression

B’chir, W., Maurin, A.-C., Carraro, V., Averous, J., Jousse, C., Muranishi, Y., Parry, L., Stepien, G., Fafournoux, P., & Bruhat, A. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt563 · Cited by 1,162

Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice

Xu, J., Lloyd, D. J., Hale, C., Stanislaus, S., Chen, M., Sivits, G., Vonderfecht, S., Hecht, R., Li, Y.-S., Lindberg, R. A., et al. (2009) · Diabetes · doi:10.2337/db08-0392 · Cited by 1,151

Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study

Mattison, J. A., Roth, G. S., Beasley, T. M., Tilmont, E. M., Handy, A. M., Herbert, R. L., Longo, D. L., Allison, D. B., Young, J. E., Bryant, M., et al. (2012) · Nature · doi:10.1038/nature11432 · Cited by 1,145

Evolution of the Fgf and Fgfr gene families.

Itoh, N., & Ornitz, D. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.08.007 · Cited by 1,123

UPR, autophagy, and mitochondria crosstalk underlies the ER stress response

Senft, D., & Ronai, Z. A. (2015) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2015.01.002 · Cited by 1,121

Fibroblast Growth Factor 21 Corrects Obesity in Mice

Coskun, T., Bina, H. A., Schneider, M. A., Dunbar, J. D., Hu, C. C., Chen, Y., Moller, D. E., & Kharitonenkov, A. (2008) · Endocrinology · doi:10.1210/en.2008-0816 · Cited by 1,031

Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2–dependent mechanisms

Shibata, R., Sato, K., Pimentel, D. R., Takemura, Y., Kihara, S., Ohashi, K., Funahashi, T., Ouchi, N., & Walsh, K. (2005) · Nature Medicine · doi:10.1038/nm1295 · Cited by 982

Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals

Hulbert, A. J., Pamplona, R., Buffenstein, R., & Buttemer, W. A. (2007) · Physiological Reviews · doi:10.1152/physrev.00047.2006 · Cited by 954

Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells

Tazawa, H., Tsuchiya, N., Izumiya, M., & Nakagama, H. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707351104 · Cited by 915

Body size, energy metabolism and lifespan

Speakman, J. R. (2005) · Journal of Experimental Biology · doi:10.1242/jeb.01556 · Cited by 914

Understanding the Physiology of FGF21

Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912

Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans

Zhang, X., Yeung, D. C. Y., Karpisek, M., Stejskal, D., Zhou, Z.-G., Liu, F., Wong, R. L. C., Chow, W.-S., Tso, A. W. K., Lam, K. S. L., et al. (2008) · Diabetes · doi:10.2337/db07-1476 · Cited by 908

AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan

Salminen, A., Hyttinen, J. M. T., & Kaarniranta, K. (2011) · Journal of Molecular Medicine · doi:10.1007/s00109-011-0748-0 · Cited by 866

PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress

Verfaillie, T., Rubio, N., Garg, A. D., Bultynck, G., Rizzuto, R., Decuypere, J.-P., Piette, J. G., Linehan, C., Gupta, S., Samali, A., et al. (2012) · Cell Death and Differentiation · doi:10.1038/cdd.2012.74 · Cited by 865

AMP-Activated Protein Kinase (AMPK) Controls the Aging Process via an Integrated Signaling Network

Salminen, A., & Kaarniranta, K. (2012) · Ageing Research Reviews · doi:10.1016/j.arr.2011.12.005 · Cited by 860

Identification of a novel FGF, FGF-21, preferentially expressed in the liver

Nishimura, T., Nakatake, Y., Konishi, M., & Itoh, N. (2000) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00067-1 · Cited by 847

Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State

Fisher, F. M., Chui, P. C., Antonellis, P. J., Bina, H. A., Kharitonenkov, A., Flier, J. S., & Maratos-Flier, E. (2010) · Diabetes · doi:10.2337/db10-0193 · Cited by 830

MicroRNA-34a regulates cardiac ageing and function.

Boon, R. A., Iekushi, K., Lechner, S., Seeger, T., Fischer, A., Heydt, S., Kaluza, D., Tréguer, K., Carmona, G., Bonauer, A., et al. (2013) · Nature · doi:10.1038/nature11919 · Cited by 821

The Critical Role of Metabolic Pathways in Aging

Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803

Mitonuclear communication in homeostasis and stress

Quirós, P. M., Mottis, A., & Auwerx, J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.23 · Cited by 787

Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine

Kim, K. H., Jeong, Y. T., Oh, H., Kim, S. H., Cho, J. M., Kim, Y.-N., Kim, S. S., Kim, D. H., Hur, K. Y., Kim, H. K., et al. (2013) · Nature Medicine · doi:10.1038/nm.3014 · Cited by 774

Stressing the role of FoxO proteins in lifespan and disease

van der Horst, A., & Burgering, B. M. T. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2190 · Cited by 759

Sirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism

Nogueiras, R., Habegger, K. M., Chaudhary, N., Finan, B., Banks, A. S., Dietrich, M. O., Horváth, T. L., Sinclair, D. A., Pfluger, P. T., & Tschöp, M. H. (2012) · Physiological Reviews · doi:10.1152/physrev.00022.2011 · Cited by 724

FGF21 induces PGC-1α and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response

Potthoff, M. J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B. N., Mangelsdorf, D. J., Kliewer, S. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904187106 · Cited by 704

Brown adipose tissue as a secretory organ

Villarroya, F., Cereijo, R., Villarroya, J., & Giralt, M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.136 · Cited by 697

Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice

Lin, Z., Tian, H., Lam, K. S. L., Lin, S., Hoo, R. C. L., Konishi, M., Itoh, N., Wang, Y., Bornstein, S. R., Xu, A., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.04.005 · Cited by 691

Adiponectin – a key adipokine in the metabolic syndrome

Whitehead, J. P., Richards, A. A., Hickman, I. J., Macdonald, G. A., & Prins, J. B. (2005) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00510.x · Cited by 655

Mitohormesis

Yun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626

Thermogenic Activation Induces FGF21 Expression and Release in Brown Adipose Tissue

Hondares, E., Iglesias, R., Giralt, A., Gonzalez, F. J., Giralt, M., Mampel, T., & Villarroya, F. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.215889 · Cited by 623

PGC1α and mitochondrial metabolism – emerging concepts and relevance in ageing and neurodegenerative disorders

Austin, S., & St‐Pierre, J. (2012) · Journal of Cell Science · doi:10.1242/jcs.113662 · Cited by 617

βKlotho is required for metabolic activity of fibroblast growth factor 21

Ogawa, Y., Kurosu, H., Yamamoto, M., Nandi, A., Rosenblatt, K. P., Goetz, R., Eliseenkova, A. V., Mohammadi, M., & Kuro-o, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701600104 · Cited by 617

Low methionine ingestion by rats extends life span.

Orentreich, N., Matias, J. R., Felice, A. D., & Zimmerman, J. (1993) · Journal of NutriLife · doi:10.1093/jn/123.2.269 · Cited by 608

FGF21 is an endocrine signal of protein restriction

Laeger, T., Henagan, T. M., Albarado, D. C., Redman, L. M., Bray, G. A., Noland, R. C., Münzberg, H., Hutson, S. M., Gettys, T. W., Schwartz, M. W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74915 · Cited by 593

Circulating FGF21 Is Liver Derived and Enhances Glucose Uptake During Refeeding and Overfeeding

Markan, K. R., Naber, M. C., Ameka, M. K., Anderegg, M. D., Mangelsdorf, D. J., Kliewer, S. A., Mohammadi, M., & Potthoff, M. J. (2014) · Diabetes · doi:10.2337/db14-0595 · Cited by 590

Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging

Salminen, A., Huuskonen, J., Ojala, J., Kauppinen, A., Kaarniranta, K., & Suuronen, T. (2008) · Ageing Research Reviews · doi:10.1016/j.arr.2007.09.002 · Cited by 581

Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK–SIRT1–PGC-1α pathway

Chau, M. D. L., Gao, J., Yang, Q., Wu, Z., & Gromada, J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006962107 · Cited by 557

Catecholaminergic systems in stress: structural and molecular genetic approaches

Kvetnansky, R., Sabban, E. L., & Palkovits, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00042.2006 · Cited by 548

Adiponectin Increases Fatty Acid Oxidation in Skeletal Muscle Cells by Sequential Activation of AMP-Activated Protein Kinase, p38 Mitogen-Activated Protein Kinase, and Peroxisome Proliferator–Activated Receptor α

Yoon, M. J., Lee, G. Y., Chung, J.-J., Ahn, Y. H., Hong, S. H., & Kim, J. B. (2006) · Diabetes · doi:10.2337/db05-1322 · Cited by 546

FGF21 regulates metabolism and circadian behavior by acting on the nervous system

Bookout, A. L., de Groot, M. H. M., Owen, B. M., Lee, S., Gautron, L., Lawrence, H. L., Ding, X., Elmquist, J. K., Takahashi, J. S., Mangelsdorf, D. J., et al. (2013) · Nature Medicine · doi:10.1038/nm.3249 · Cited by 545

Fibroblast Growth Factor-21 Regulates PPARγ Activity and the Antidiabetic Actions of Thiazolidinediones

Dutchak, P. A., Katafuchi, T., Bookout, A. L., Choi, J. H., Yu, R. T., Mangelsdorf, D. J., & Kliewer, S. A. (2012) · Cell · doi:10.1016/j.cell.2011.11.062 · Cited by 537

Autophagy and aging: keeping that old broom working

Cuervo, A. M. (2008) · Trends in Genetics · doi:10.1016/j.tig.2008.10.002 · Cited by 527

An FGF21-Adiponectin-Ceramide Axis Controls Energy Expenditure and Insulin Action in Mice

Holland, W., Adams, A., Brozinick, J., Bui, H., Miyauchi, Y., Kusminski, C., Bauer, S., Wade, M., Singhal, E., Cheng, C. C., et al. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.019 · Cited by 525

FGF21 acts centrally to induce sympathetic nerve activity, energy expenditure, and weight loss

Owen, B. M., Ding, X., Morgan, D. A., Coate, K. C., Bookout, A. L., Rahmouni, K., Kliewer, S. A., & Mangelsdorf, D. J. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.012 · Cited by 523

The Effect of Age on Thymic Function

Palmer, D. B. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00316 · Cited by 494

Eukaryotic Initiation Factor 2 Phosphorylation and Translational Control in Metabolism

Baird, T. D., & Wek, R. C. (2012) · Advances in Nutrition · doi:10.3945/an.112.002113 · Cited by 486

AMPK at the Nexus of Energetics and Aging

Burkewitz, K., Zhang, Y., & Mair, W. B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.002 · Cited by 483

FGF-21 as a biomarker for muscle-manifesting mitochondrial respiratory chain deficiencies: a diagnostic study

Suomalainen, A., Elo, J. M., Pietiläinen, K. H., Hakonen, A. H., Sevastianova, K., Korpela, M., Isohanni, P., Marjavaara, S. K., Tyni, T., Kiuru-Enari, S., et al. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70155-7 · Cited by 427

Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ

Wei, W., Dutchak, P. A., Wang, X., Ding, X., Wang, X., Bookout, A. L., Goetz, R., Mohammadi, M., Gerard, R. D., Dechow, P. C., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1200797109 · Cited by 426

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

Zhang, Y., Xie, Y., Berglund, E. D., Coate, K. C., He, T. T., Katafuchi, T., Xiao, G., Potthoff, M. J., Wei, W., Wan, Y., et al. (2012) · eLife · doi:10.7554/elife.00065 · Cited by 420

Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21

Inagaki, T., Lin, V. Y., Goetz, R., Mohammadi, M., Mangelsdorf, D. J., & Kliewer, S. A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.05.006 · Cited by 409

βKlotho Is Required for Fibroblast Growth Factor 21 Effects on Growth and Metabolism

Ding, X., Boney-Montoya, J., Owen, B. M., Bookout, A. L., Coate, K. C., Mangelsdorf, D. J., & Kliewer, S. A. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.08.002 · Cited by 403

Regulation of autophagy by ATF4 in response to severe hypoxia

Rzymski, T., Milani, M., Pike, L., Buffa, F. M., Mellor, H. R., Winchester, L. M., Pires, I. M., Hammond, E. M., Ragoussis, J., & Harris, A. L. (2010) · Oncogene · doi:10.1038/onc.2010.191 · Cited by 402

Caloric restriction, SIRT1 and longevity

Cantó, C., & Auwerx, J. (2009) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2009.03.008 · Cited by 395

Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB

Mair, W., Morantte, I., Rodrigues, A. P. C., Manning, G., Montminy, M., Shaw, R. J., & Dillin, A. (2011) · Nature · doi:10.1038/nature09706 · Cited by 393

Fibroblast growth factor 21 protects against cardiac hypertrophy in mice

Planavila, A., Redondo‐Angulo, I., Hondares, E., Vinciguerra, M., Munts, C., Iglesias, R., Gabrielli, L., Sitges, M., Giralt, M., van Bilsen, M., et al. (2013) · Nature Communications · doi:10.1038/ncomms3019 · Cited by 371

Mitochondrial stress induces chromatin reorganization to promote longevity and UPR(mt)

Tian, Y., Garcia, G., Bian, Q., Steffen, K. K., Joe, L., Wolff, S., Meyer, B. J., & Dillin, A. (2016) · Cell · doi:10.1016/j.cell.2016.04.011 · Cited by 370

Fibroblast Growth Factor 21-Deficient Mice Demonstrate Impaired Adaptation to Ketosis

Badman, M. K., Koester, A., Flier, J. S., Kharitonenkov, A., & Maratos-Flier, E. (2009) · Endocrinology · doi:10.1210/en.2009-0532 · Cited by 362

PPARα is a key regulator of hepatic FGF21

Lundåsen, T., Hunt, M., Nilsson, L.-M., Sanyal, S., Angelin, B., Alexson, S., & Rudling, M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.06.068 · Cited by 361

The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila

Liu, N., Landreh, M., Cao, K., Abe, M., Hendriks, G.-J., Kennerdell, J. R., Zhu, Y., Wang, L.-S., & Bonini, N. M. (2012) · Nature · doi:10.1038/nature10810 · Cited by 356

βKlotho Is Required for Fibroblast Growth Factor (FGF) 21 Signaling through FGF Receptor (FGFR) 1c and FGFR3c

Suzuki, M., Uehara, Y., Motomura-Matsuzaka, K., Oki, J., Koyama, Y., Kimura, M., Asada, M., Komi-Kuramochi, A., Oka, S., & Toru, T. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0313 · Cited by 345

Evolutionary conservation of the clk-1 -dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice

Liu, X., Jiang, N., Hughes, B., Bigras, E., Shoubridge, E., & Hekimi, S. (2005) · Genes & Development · doi:10.1101/gad.1352905 · Cited by 345

MicroRNA-34a regulation of endothelial senescence

Ito, T., Yagi, S., & Yamakuchi, M. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.07.012 · Cited by 340

FGF‐21/FGF‐21 receptor interaction and activation is determined by βKlotho

Kharitonenkov, A., Dunbar, J. D., Bina, H. A., Bright, S. W., Moyers, J. S., Zhang, C., Ding, L., Micanovic, R., Mehrbod, S. F., Knierman, M. D., et al. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21357 · Cited by 333

Adiponectin actions in the cardiovascular system

Hopkins, T. A., Ouchi, N., Shibata, R., & Walsh, K. X. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.10.009 · Cited by 331

The metabolic regulation of aging

Finkel, T. (2015) · Nature Medicine · doi:10.1038/nm.3998 · Cited by 325

Obesity accelerates thymic aging

Yang, H., Youm, Y., Vandanmagsar, B., Rood, J. C., Kumar, K. G., Butler, A. A., & Dixit, V. D. (2009) · Blood · doi:10.1182/blood-2009-03-213595 · Cited by 314

AMPK as a mediator of hormonal signalling

Lim, C. T., Kola, B., & Korbonits, M. (2009) · Journal of Molecular Endocrinology · doi:10.1677/jme-09-0063 · Cited by 304

Fibroblast Growth Factor 21 as an emerging metabolic regulator: clinical perspectives

Woo, Y. C., Xu, A., Wang, Y., & Lam, K. S. L. (2012) · Clinical Endocrinology · doi:10.1111/cen.12095 · Cited by 302

Mitochondrial myopathy induces a starvation-like response

Tyynismaa, H., Carroll, C. J., Raimundo, N., Ahola-Erkkilä, S., Wenz, T., Ruhanen, H., Guse, K., Hemminki, A., Peltola-Mjøsund, K. E., Tulkki, V., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq310 · Cited by 300

FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting

Liang, Q., Zhong, L., Zhang, J., Wang, Y., Bornstein, S. R., Triggle, C. R., Ding, H., Lam, K. S. L., & Xu, A. (2014) · Diabetes · doi:10.2337/db14-0541 · Cited by 299

Somatotropic Signaling: Trade-Offs Between Growth, Reproductive Development, and Longevity

Bartke, A., Sun, L. Y., & Longo, V. D. (2013) · Physiological Reviews · doi:10.1152/physrev.00006.2012 · Cited by 296

Adipose Fibroblast Growth Factor 21 Is Up-Regulated by Peroxisome Proliferator-Activated Receptor γ and Altered Metabolic States

Muise, E. S., Azzolina, B., Kuo, D. W., El-Sherbeini, M., Tan, Y., Yuan, X., Mu, J., Thompson, J. R., Berger, J. P., & Wong, K. K. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.044826 · Cited by 294

Calorie restriction and prevention of age‐associated chronic disease

Omodei, D., & Fontana, L. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.03.015 · Cited by 293

The multifaceted role of mTORC1 in the control of lipid metabolism

Ricoult, S. J. H., & Manning, B. D. (2013) · EMBO Reports · doi:10.1038/embor.2013.5 · Cited by 291

Adiponectin receptor signalling in the brain

Thundyil, J., Pavlovski, D., Sobey, C. G., & Arumugam, T. V. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01560.x · Cited by 289

Myokines and Adipokines: Involvement in the Crosstalk between Skeletal Muscle and Adipose Tissue

Li, F., Li, Y., Duan, Y., Hu, C.-A. A., Tang, Y., & Yin, Y. (2017) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.10.003 · Cited by 288

The fasting polypeptide FGF21 can enter brain from blood

Hsuchou, H., Pan, W., & Kastin, A. J. (2007) · Peptides · doi:10.1016/j.peptides.2007.10.007 · Cited by 280

Regulation of the aging process by autophagy.

Salminen, A., & Kaarniranta, K. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.03.004 · Cited by 270

Fibroblast growth factor 21 protects the heart from oxidative stress

Planavila, A., Redondo‐Angulo, I., Ribas‐Aulinas, F., Garrabou, G., Casademont, J., Giralt, M., & Villarroya, F. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu263 · Cited by 265

Interplay between FGF21 and insulin action in the liver regulates metabolism

Emanuelli, B., Vienberg, S. G., Smyth, G., Cheng, C., Stanford, K. I., Arumugam, M., Michael, M. D., Adams, A. C., Kharitonenkov, A., & Kahn, C. R. (2014) · Journal of Clinical Investigation · doi:10.1172/jci67353 · Cited by 251

Protein and amino acid restriction, aging and disease: from yeast to humans

Mirzaei, H., Suarez, J. A., & Longo, V. D. (2014) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2014.07.002 · Cited by 249

Activating transcription factor 4-dependent induction of FGF21 during amino acid deprivation

De Sousa-Coelho, A. L., Marrero, P. F., & Haro, D. (2012) · Biochemical Journal · doi:10.1042/bj20111748 · Cited by 246

Hormone-like (endocrine) Fgfs: their evolutionary history and roles in development, metabolism, and disease

Itoh, N. (2010) · Cell and Tissue Research · doi:10.1007/s00441-010-1024-2 · Cited by 241

Dietary restriction in rats and mice: A meta-analysis and review of the evidence for genotype-dependent effects on lifespan

Swindell, W. R. (2011) · Ageing Research Reviews · doi:10.1016/j.arr.2011.12.006 · Cited by 236

The Th17/Treg balance is disturbed during aging

Schmitt, V., Rink, L., & Uciechowski, P. (2013) · Experimental Gerontology · doi:10.1016/j.exger.2013.09.003 · Cited by 235

Cellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice

Camporez, J. P., Jornayvaz, F. R., Petersen, M. C., Pesta, D. H., Guigni, B. A., Serr, J., Zhang, D., Kahn, M., Samuel, V. T., Jurczak, M. J., et al. (2013) · Endocrinology · doi:10.1210/en.2013-1191 · Cited by 232

Adiponectin Stimulates Autophagy and Reduces Oxidative Stress to Enhance Insulin Sensitivity During High-Fat Diet Feeding in Mice

Liu, Y., Palanivel, R., Rai, E., Park, M. S., Gabor, T. V., Scheid, M. P., Xu, A., & Sweeney, G. (2014) · Diabetes · doi:10.2337/db14-0267 · Cited by 223

Stress Biology and Aging Mechanisms: Toward Understanding the Deep Connection Between Adaptation to Stress and Longevity

Epel, E. S., & Lithgow, G. J. (2014) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glu055 · Cited by 223

Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the induction of FGF21 as a myokine

Keipert, S., Ost, M., Johann, K., Imber, F., Jastroch, M., van Schothorst, E. M., Keijer, J., & Klaus, S. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00330.2013 · Cited by 221

Aging networks in Caenorhabditis elegans : AMP‐activated protein kinase ( aak‐2 ) links multiple aging and metabolism pathways

Curtis, R., O'Connor, G., & DiStefano, P. S. (2006) · Aging Cell · doi:10.1111/j.1474-9726.2006.00205.x · Cited by 220

Deletion of the Mammalian INDY Homolog Mimics Aspects of Dietary Restriction and Protects against Adiposity and Insulin Resistance in Mice

Birkenfeld, A. L., Lee, H., Guebre‐Egziabher, F., Alves, T. C., Jurczak, M. J., Jornayvaz, F. R., Zhang, D., Hsiao, J. J., Martín‐Montalvo, A., Fischer‐Rosinsky, A., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.06.009 · Cited by 217

Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice

Douris, N., Stevanovic, D. M., Fisher, F. M., Cisu, T. I., Chee, M. J., Nguyen, N. L., Zarebidaki, E., Adams, A. C., Kharitonenkov, A., Flier, J. S., et al. (2015) · Endocrinology · doi:10.1210/en.2014-2001 · Cited by 215

FGF21 and the late adaptive response to starvation in humans

Fazeli, P. K., Lun, M., Kim, S. M., Bredella, M. A., Wright, S., Zhang, Y., Lee, H., Catana, C., Klibanski, A., Patwari, P., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci83349 · Cited by 214

Opposite alterations in FGF21 and FGF19 levels and disturbed expression of the receptor machinery for endocrine FGFs in obese patients

Gallego-Escuredo, J. M., Gómez‐Ambrosi, J., Catalán, V., Domingo, P., Giralt, M., Frühbeck, G., & Villarroya, F. (2014) · International Journal of Obesity · doi:10.1038/ijo.2014.76 · Cited by 212

Increased expression of miR-34a and miR-93 in rat liver during aging, and their impact on the expression of Mgst1 and Sirt1

Li, N., Muthusamy, S., Liang, R., Sarojini, H., & Wang, E. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.12.004 · Cited by 211

The impact of low-protein high-carbohydrate diets on aging and lifespan

Le Couteur, D. G., Solon-Biet, S., Cogger, V. C., Mitchell, S. J., Senior, A., de Cabo, R., Raubenheimer, D., & Simpson, S. J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2120-y · Cited by 209

Hypoxic Reactive Oxygen Species Regulate the Integrated Stress Response and Cell Survival

Liu, L., Wise, D. R., Diehl, J. A., & Simon, M. C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805056200 · Cited by 206

Metabolic Responses to Dietary Protein Restriction Require an Increase in FGF21 that Is Delayed by the Absence of GCN2

Laeger, T., Albarado, D. C., Burke, S. J., Trosclair, L., Hedgepeth, J. W., Berthoud, H.-R., Gettys, T. W., Collier, J. J., Münzberg, H., & Morrison, C. D. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.044 · Cited by 206

The role of mitochondrial dysfunction in age-related diseases

Lane, R. K., Hilsabeck, T., & Rea, S. L. (2015) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2015.05.021 · Cited by 205

Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21

Lees, E. K., Król, E., Grant, L., Shearer, K., Wyse, C. A., Moncur, E. M., Bykowska, A. S., Mody, N., Gettys, T. W., & Delibegović, M. (2014) · Aging Cell · doi:10.1111/acel.12238 · Cited by 203

The PPARα-FGF21 Hormone Axis Contributes to Metabolic Regulation by the Hepatic JNK Signaling Pathway

Vernia, S., Cavanagh, J., García-Haro, L., Sabio, G., Barrett, T., Jung, D. Y., Kim, J. K., Xu, J. L., Shulha, H. P., Garber, M. G., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.06.010 · Cited by 200

TNF-α Represses β-Klotho Expression and Impairs FGF21 Action in Adipose Cells: Involvement of JNK1 in the FGF21 Pathway

Díaz-Delfín, J., Hondares, E., Iglesias, R., Giralt, M., Caelles, C., & Villarroya, F. (2012) · Endocrinology · doi:10.1210/en.2012-1193 · Cited by 199

Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease

Yilmaz, Y. N., Eren, F., Yönal, O., Kurt, R., Aktaş, B., Çelikel, Ç., Özdogan, O. C., İmeryüz, N., Kalaycı, C., & Avşar, E. (2010) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2010.02338.x · Cited by 197

Inhibition of Thymic Adipogenesis by Caloric Restriction Is Coupled with Reduction in Age-Related Thymic Involution

Yang, H., Youm, Y.-H., & Dixit, V. D. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900562 · Cited by 196

Longevity and stress in Caenorhabditis elegans

Zhou, K. I., Pincus, Z., & Slack, F. J. (2011) · Aging · doi:10.18632/aging.100367 · Cited by 196

Serum Fibroblast Growth Factor-21 Levels Are Associated With Carotid Atherosclerosis Independent of Established Cardiovascular Risk Factors

Chow, W. S., Xu, A., Woo, Y. C., Tso, A. W. K., Cheung, S., Fong, C. H.-Y., Tse, H., Chau, M. T., Cheung, B. M. Y., & Lam, K. S. L. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301599 · Cited by 193

MicroRNA 34a Inhibits Beige and Brown Fat Formation in Obesity in Part by Suppressing Adipocyte Fibroblast Growth Factor 21 Signaling and SIRT1 Function

Fu, T., Seok, S., Choi, S., Huang, Z., Suino-Powell, K. M., Xu, H. E., KEMPER, B. W., & Kemper, J. K. (2014) · Molecular and Cellular Biology · doi:10.1128/mcb.00596-14 · Cited by 190

Amelioration of Type 2 Diabetes by Antibody-Mediated Activation of Fibroblast Growth Factor Receptor 1

Wu, A.-L., Kolumam, G., Stawicki, S., Chen, Y., Li, J., Zavala-Solorio, J., Phamluong, K., Feng, B., Li, L., Marsters, S., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002669 · Cited by 184

Circulatory miR-34a as an RNA-based, noninvasive biomarker for brain aging

Li, X., Khanna, A., Li, N., & Wang, E. (2011) · Aging · doi:10.18632/aging.100371 · Cited by 184

Fibroblast Growth Factor 21 Is Regulated by the IRE1α-XBP1 Branch of the Unfolded Protein Response and Counteracts Endoplasmic Reticulum Stress-induced Hepatic Steatosis

Jiang, S., Cheng, Y., Fang, Q., Shao, M., Zhang, Y., Liu, Y., Deng, Y., Shan, B., Liu, J., Li, H., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.565960 · Cited by 182

Fibroblast growth factor 21 (FGF21) inhibits macrophage-mediated inflammation by activating Nrf2 and suppressing the NF-κB signaling pathway

Yu, Y.-H., He, J., Li, S., Song, L., Guo, X., Yao, W., Zou, D., Gao, X., Liu, Y., Bai, F., et al. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.05.026 · Cited by 182

Endocrine Protection of Ischemic Myocardium by FGF21 from the Liver and Adipose Tissue

Liu, S. Q., Roberts, D., Kharitonenkov, A., Zhang, B., Hanson, S., Li, Y. C., Zhang, L., & Wu, Y. (2013) · Scientific Reports · doi:10.1038/srep02767 · Cited by 179

AMP‐activated protein kinase mediates glucocorticoid‐ induced metabolic changes: a novel mechanism in Cushing's syndrome

Christ‐Crain, M., Kola, B., Lolli, F., Fekete, C., Seboek, D., Wittmann, G., Feltrin, D., Igreja, S., Ajodha, S. J., Harvey-White, J. D., et al. (2008) · The FASEB Journal · doi:10.1096/fj.07-094144 · Cited by 175

MicroRNA-34a regulates the longevity-associated protein SIRT1 in coronary artery disease: effect of statins on SIRT1 and microRNA-34a expression

Tabuchi, T., Satoh, M., Itoh, T., & Nakamura, M. (2012) · Clinical Science · doi:10.1042/cs20110563 · Cited by 174

Fibroblast growth factor 21 improves hepatic insulin sensitivity by inhibiting mammalian target of rapamycin complex 1 in mice

Gong, Q., Hu, Z., Zhang, F., Cui, A., Chen, X., Jiang, H., Gao, J., Chen, X., Han, Y., Liang, Q., et al. (2016) · Hepatology · doi:10.1002/hep.28523 · Cited by 171

A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution

Maida, A., Zota, A., Sjøberg, K. A., Schumacher, J., Sijmonsma, T. P., Pfenninger, A., Christensen, M. M., Gantert, T., Fuhrmeister, J., Rothermel, U., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85946 · Cited by 170

Mitochondrial uncoupling and lifespan

Mookerjee, S. A., Divakaruni, A. S., Jastroch, M., & Brand, M. D. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.03.010 · Cited by 169

A liver-bone endocrine relay by IGFBP1 promotes osteoclastogenesis and mediates FGF21-induced bone resorption

Wang, X., Wei, W., Krzeszinski, J. Y., Wang, Y., & Wan, Y. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.010 · Cited by 165

Calorie restriction mimetics: Can you have your cake and eat it, too?

Ingram, D. K., & Roth, G. S. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.11.005 · Cited by 164

Fibroblast growth factor 21 is induced by endoplasmic reticulum stress

Schaap, F. G., Kremer, A. E., Lamers, W. H., Jansen, P. L. M., & Gaemers, I. C. (2012) · Biochimie · doi:10.1016/j.biochi.2012.10.019 · Cited by 164

FGF21-based pharmacotherapy – potential utility for metabolic disorders

Gimeno, R. E., & Moller, D. E. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2014.03.001 · Cited by 163

MiR-34 modulates Caenorhabditis elegans lifespan via repressing the autophagy gene atg9

Yang, J., Chen, D., He, Y., Meléndez, A., Feng, Z., Hong, Q., Bai, X., Li, Q., Cai, G., Wang, J., et al. (2011) · AGE · doi:10.1007/s11357-011-9324-3 · Cited by 161

Fenofibrate increases cardiac autophagy via FGF21/SIRT1 and prevents fibrosis and inflammation in the hearts of Type 1 diabetic mice

Zhang, J., Cheng, Y., Gu, J., Wang, S., Zhou, S., Wang, Y., Tan, Y., Feng, W., Fu, Y., Mellen, N. M., et al. (2016) · Clinical Science · doi:10.1042/cs20150623 · Cited by 161

Adiponectin signaling in the liver

Combs, T. P., & Marliss, E. B. (2013) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-013-9280-6 · Cited by 160

Transcriptional up-regulation of ULK1 by ATF4 contributes to cancer cell survival

Pike, L., Singleton, D. C., Buffa, F. M., Abramczyk, O., Phadwal, K., Li, J., Simon, A. K., Murray, J. T., & Harris, A. L. (2012) · Biochemical Journal · doi:10.1042/bj20120972 · Cited by 158

Tipping the metabolic scales towards increased longevity in mammals

Riera, C. E., & Dillin, A. (2015) · Nature Cell Biology · doi:10.1038/ncb3107 · Cited by 153

Mitochondria and PGC-1α in Aging and Age-Associated Diseases

Wenz, T. (2011) · Journal of Aging Research · doi:10.4061/2011/810619 · Cited by 152

Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21

Cornu, M., Oppliger, W., Albert, V., Robitaille, A. M., Trapani, F., Quagliata, L., Fuhrer, T., Sauer, U., Terracciano, L., & Hall, M. N. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1412047111 · Cited by 152

Fibroblast growth factor-21, energy balance and obesity

Giralt, M., Gavaldà‐Navarro, A., & Villarroya, F. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.09.018 · Cited by 150

Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19 by targeting a membrane coreceptor β-Klotho

Fu, T., Choi, S., Kim, D.-H., Seok, S., Suino-Powell, K. M., Xu, H. E., & Kemper, J. K. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205951109 · Cited by 150

The somatotropic axis in human aging: framework for the current state of knowledge and future research

Milman, S., Huffman, D. M., & Barzilai, N. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.014 · Cited by 150

Visions & Reflections¶Regulation of longevity and stress resistance: a molecular strategy conserved from yeast to humans?

Longo, V. D., & Fabrizio, P. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8477-8 · Cited by 147

Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism

Liu, Q., Yuan, B., Lo, K. A., Patterson, H. C., Sun, Y., & Lodish, H. F. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211611109 · Cited by 144

Endocrine FGFs and Klothos: emerging concepts

Kuro‐o, M. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.06.002 · Cited by 141

Growth Hormone Induces Hepatic Production of Fibroblast Growth Factor 21 through a Mechanism Dependent on Lipolysis in Adipocytes

Chen, W., Hoo, R. L. C., Konishi, M., Itoh, N., Lee, P.-C., Ye, H., Lam, K. S. L., & Xu, A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.285965 · Cited by 141

Disruption of mitochondrial fission in the liver protects mice from diet-induced obesity and metabolic deterioration

Wang, L., Ishihara, T., Ibayashi, Y., Tatsushima, K., Setoyama, D., Hanada, Y., Takeichi, Y., Sakamoto, S., Yokota, S., Mihara, K., et al. (2015) · Diabetologia · doi:10.1007/s00125-015-3704-7 · Cited by 138

MicroRNA-34a Induces Vascular Smooth Muscle Cells Senescence by SIRT1 Downregulation and Promotes the Expression of Age-Associated Pro-inflammatory Secretory Factors

Badi, I., Burba, I., Ruggeri, C., Zeni, F., Bertolotti, M., Scopece, A., Pompilio, G., & Raucci, A. (2014) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu180 · Cited by 136

FGF21 Is an Exocrine Pancreas Secretagogue

Coate, K. C., Hernandez, G., Thorne, C. A., Sun, S., Le, T. D. V., Vale, K., Kliewer, S. A., & Mangelsdorf, D. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.004 · Cited by 136

DEC1, a Basic Helix-Loop-Helix Transcription Factor and a Novel Target Gene of the p53 Family, Mediates p53-dependent Premature Senescence

Qian, Y., Zhang, J., Yan, B., & Chen, X. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m708624200 · Cited by 135

Prolongevity hormone FGF21 protects against immune senescence by delaying age-related thymic involution

Youm, Y.-H., Horvath, T. L., Mangelsdorf, D. J., Kliewer, S. A., & Dixit, V. D. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514511113 · Cited by 129

Fibroblast growth factor 21 participates in adaptation to endoplasmic reticulum stress and attenuates obesity-induced hepatic metabolic stress

Kim, S. H., Kim, K. H., Kim, H.-K., Kim, M.-J., Back, S. H., Konishi, M., Itoh, N., & Lee, M.-S. (2015) · Diabetologia · doi:10.1007/s00125-014-3475-6 · Cited by 124

Novel Insights into the Cardio-Protective Effects of FGF21 in Lean and Obese Rat Hearts

Patel, V., Adya, R., Chen, J., Ramanjaneya, M., Bari, M. F., Bhudia, S. K., Hillhouse, E. W., Tan, B. K., & Randeva, H. S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087102 · Cited by 124

ER stress and hormetic regulation of the aging process

Salminen, A., & Kaarniranta, K. (2010) · Ageing Research Reviews · doi:10.1016/j.arr.2010.04.003 · Cited by 122

mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes

Minard, A. Y., Tan, S., Yang, P., Fazakerley, D. J., Domanova, W., Parker, B. L., Humphrey, S. J., Jothi, R., Stöckli, J., & James, D. E. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.086 · Cited by 122

FGF21 activates AMPK signaling: impact on metabolic regulation and the aging process

Salminen, A., Kauppinen, A., & Kaarniranta, K. (2016) · Journal of Molecular Medicine · doi:10.1007/s00109-016-1477-1 · Cited by 121

Fibroblast growth factor 21 protects mouse brain against d-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation

Yu, Y., Bai, F., Wang, W., Liu, Y., Yuan, Q., Qu, S., Zhang, T., Tian, G., Li, S., Li, D., et al. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.03.020 · Cited by 119

Fibroblast growth factor-21 enhances mitochondrial functions and increases the activity of PGC-1α in human dopaminergic neurons via Sirtuin-1

Mäkelä, J., Tselykh, T. V., Maiorana, F., Eriksson, O., Thi, H., Mudò, G., Korhonen, L., Belluardo, N., & Lindholm, D. (2014) · SpringerPlus · doi:10.1186/2193-1801-3-2 · Cited by 119

Adenosine Monophosphate-activated Protein Kinase Induces Cholesterol Efflux from Macrophage-derived Foam Cells and Alleviates Atherosclerosis in Apolipoprotein E-deficient Mice*

Li, D., Wang, D., Wang, Y., Ling, W., Feng, X., & Xia, M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.159772 · Cited by 115

Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21

Domouzoglou, E. M., Naka, K. Κ., Vlahos, A. P., Papafaklis, M. I., Michalis, L. K., Tsatsoulis, A., & Maratos–Flier, E. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00527.2015 · Cited by 115

FGF21 attenuates pathological myocardial remodeling following myocardial infarction through the adiponectin-dependent mechanism

Joki, Y., Ohashi, K., Yuasa, D., Shibata, R., Ito, M., Matsuo, K., Kambara, T., Uemura, Y., Hayakawa, S., Hiramatsu‐Ito, M., et al. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.02.081 · Cited by 114

FGF21 Revolutions: Recent Advances Illuminating FGF21 Biology and Medicinal Properties

Kharitonenkov, A., & DiMarchi, R. D. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.007 · Cited by 114

Fibroblast growth factor 21 protects the heart from apoptosis in a diabetic mouse model via extracellular signal-regulated kinase 1/2-dependent signalling pathway

Zhang, C., Huang, Z., Gu, J., Yan, X., Lu, X., Zhou, S., Wang, S., Shao, M., Zhang, F., Cheng, P., et al. (2015) · Diabetologia · doi:10.1007/s00125-015-3630-8 · Cited by 113

Metformin-induced inhibition of the mitochondrial respiratory chain increases FGF21 expression via ATF4 activation

Kim, K. H., Jeong, Y. T., Kim, S. H., Jung, H. S., Park, K. S., Lee, H.-Y., & Lee, M.-S. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.09.026 · Cited by 112

High Glucose Represses β-Klotho Expression and Impairs Fibroblast Growth Factor 21 Action in Mouse Pancreatic Islets

So, W. Y., Cheng, Q., Chen, L., Evans‐Molina, C., Xu, A., Lam, K. S. L., & Leung, P. S. (2013) · Diabetes · doi:10.2337/db13-0645 · Cited by 112

Fibroblast Growth Factor 21 (FGF21) Protects against High Fat Diet Induced Inflammation and Islet Hyperplasia in Pancreas

Singhal, G., Fisher, F. M., Chee, M. J. S., Tan, T. G., Ouaamari, A. E., Adams, A. C., Najarían, R. M., Kulkarni, R., Benoist, C. O., Flier, J. S., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0148252 · Cited by 112

ATF4- and CHOP-Dependent Induction of FGF21 through Endoplasmic Reticulum Stress

Wan, X., Lu, X., Xiao, Y.-C., Lin, Y., Zhu, H., Ding, T., Yang, Y., Huang, Y., Zhang, Y., Liu, Y., et al. (2014) · BioMed Research International · doi:10.1155/2014/807874 · Cited by 110

Mechanisms of Aging-Related Impairment of Brown Adipocyte Development and Function

Graja, A., & Schulz, T. J. (2014) · Gerontology · doi:10.1159/000366557 · Cited by 105

FGF21 mediates alcohol-induced adipose tissue lipolysis by activation of systemic release of catecholamine in mice

Zhao, C., Liu, Y., Xiao, J., Liu, L., Chen, S., Mohammadi, M., McClain, C. J., Li, X., & Feng, W. (2015) · Journal of Lipid Research · doi:10.1194/jlr.m058610 · Cited by 105

Circulating levels of fibroblast growth factor-21 increase with age independently of body composition indices among healthy individuals

Hanks, L. J., Gutiérrez, O. M., Bamman, M. M., Ashraf, A., McCormick, K. L., & Casazza, K. (2015) · Journal of Clinical & Translational Endocrinology · doi:10.1016/j.jcte.2015.02.001 · Cited by 104

The paradox of mitochondrial dysfunction and extended longevity

Munkácsy, E., & Rea, S. L. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.03.016 · Cited by 104

The FGF21–adiponectin axis in controlling energy and vascular homeostasis

Hui, X. H., Feng, T., Liu, Q., Gao, Y., & Xu, A. (2016) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjw013 · Cited by 103

Glucocorticoids Regulate the Metabolic Hormone FGF21 in a Feed-Forward Loop

Patel, R., Bookout, A. L., Magomedova, L., Owen, B. M., Consiglio, G. P., Shimizu, M., Zhang, Y., Mangelsdorf, D. J., Kliewer, S. A., & Cummins, C. L. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1259 · Cited by 102

Attenuation of Hyperlipidemia- and Diabetes-Induced Early-Stage Apoptosis and Late-Stage Renal Dysfunction via Administration of Fibroblast Growth Factor-21 Is Associated with Suppression of Renal Inflammation

Zhang, C., Shao, M., Yang, H., Chen, L., Yu, L., Cong, W., Tian, H., Zhang, F., Cheng, P., Jin, L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0082275 · Cited by 100

Activation of mTORC1 in skeletal muscle regulates whole-body metabolism through FGF21

Guridi, M., Tintignac, L. A. J., Lin, S., Kupr, B., Castets, P., & Rüegg, M. A. (2015) · Science Signaling · doi:10.1126/scisignal.aab3715 · Cited by 98

Adiponectin Increases Skeletal Muscle Mitochondrial Biogenesis by Suppressing Mitogen-Activated Protein Kinase Phosphatase-1

Qiao, L., Kinney, B., Yoo, H. S., Lee, B., Schaack, J. B., & Shao, J. (2012) · Diabetes · doi:10.2337/db11-1475 · Cited by 97

Fibroblast growth factor 21 attenuates hepatic fibrogenesis through TGF-β/smad2/3 and NF-κB signaling pathways

Xu, P., Zhang, Y., Liu, Y., Yuan, Q., Song, L., Liu, M., Liu, Z., Yang, Y., Li, J., Li, D., et al. (2016) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2015.11.012 · Cited by 97

Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice

Rusli, F., Deelen, J., Andriyani, E., Boekschoten, M. V., Lute, C., van den Akker, E. B., Müller, M. M., Beekman, M., & Steegenga, W. T. (2016) · Scientific Reports · doi:10.1038/srep30484 · Cited by 96

Circulating Fibroblast Growth Factor 21 Levels Are Closely Associated with Hepatic Fat Content: A Cross-Sectional Study

Yan, H., Xia, M., Chang, X., Xu, Q., Bian, H., Zeng, M., Rao, S., Yao, X., Tu, Y., Jia, W., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024895 · Cited by 95

Skeletal muscle increases FGF21 expression in mitochondrial disorders to compensate for energy metabolic insufficiency by activating the mTOR–YY1–PGC1α pathway

Ji, K., Zheng, J., Lv, J., Xu, J., Ji, X., Luo, Y., Li, W. S., Zhao, Y., & Yan, C. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.03.020 · Cited by 95

Anti-Inflammatory Mechanisms of Dietary Restriction in Slowing Aging Processes

Morgan, T. E., Wong, A., & Finch, C. E. (2006) · KARGER eBooks · doi:10.1159/000096557 · Cited by 94

Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease

Gates, A. C., Bernal-Mizrachi, C., Chinault, S. L., Feng, C., Schneider, J. G., Coleman, T., Malone, J. P., Townsend, R. R., Chakravarthy, M. V., & Semenkovich, C. F. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.010 · Cited by 94

Fibroblast Growth Factor 21 (FGF21) Inhibits Chondrocyte Function and Growth Hormone Action Directly at the Growth Plate

Wu, S., Levenson, A. E., Kharitonenkov, A., & Luca, F. D. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.343707 · Cited by 94

Mitochondrial dysfunction enhances cisplatin resistance in human gastric cancer cells via the ROS-activated GCN2-eIF2α-ATF4-xCT pathway

Wang, S., Chen, M.-S., Chou, Y., Ueng, Y., Yin, P., Yeh, T.-S., & Lee, H. (2016) · Oncotarget · doi:10.18632/oncotarget.12356 · Cited by 93

Impaired Mitochondrial Fat Oxidation Induces FGF21 in Muscle

Vandanmagsar, B., Warfel, J. D., Wicks, S. E., Ghosh, S., Salbaum, J. M., Burk, D., Dubuisson, O. S., Mendoza, T. M., Zhang, J., Noland, R. C., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.04.057 · Cited by 92

FGF21 as an Endocrine Regulator in Lipid Metabolism: From Molecular Evolution to Physiology and Pathophysiology

Murata, Y., Konishi, M., & Itoh, N. (2011) · Journal of Nutrition and Metabolism · doi:10.1155/2011/981315 · Cited by 87

Curcumin Enhanced Cholesterol Efflux by Upregulating ABCA1 Expression Through AMPK-SIRT1-LXRα Signaling in THP-1 Macrophage-Derived Foam Cells

Lin, X., Liu, M., Hu, H.-J., Feng, H., Fan, X., Zou, W.-W., Pan, Y., Hu, X., & Wang, Z. (2015) · DNA and Cell Biology · doi:10.1089/dna.2015.2866 · Cited by 86

Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB

Lee, M. S., Choi, S., Ha, E. S., An, S.-Y., Kim, T. H., Han, S. J., Kim, H. J., Kim, D. J., KANG, Y. Y., & Lee, K. W. (2012) · Metabolism · doi:10.1016/j.metabol.2012.01.012 · Cited by 80

Fibroblast growth factor 21 (FGF21) ameliorates collagen-induced arthritis through modulating oxidative stress and suppressing nuclear factor-kappa B pathway

Yu, Y.-H., Li, S., Liu, Y., Tian, G., Yuan, Q., Bai, F., Wang, W., Zhang, Z., Ren, G., Zhang, Y., et al. (2015) · International Immunopharmacology · doi:10.1016/j.intimp.2015.01.005 · Cited by 78

FGF21-Mediated Improvements in Glucose Clearance Require Uncoupling Protein 1

Kwon, M. M., O’Dwyer, S. M., Baker, R. K., Covey, S. D., & Kieffer, T. J. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.021 · Cited by 77

Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents

Perrone, C. E., Malloy, V. L., Orentreich, D. S., & Orentreich∥, N. (2012) · Experimental Gerontology · doi:10.1016/j.exger.2012.07.005 · Cited by 76

Targeting Autophagy in Aging and Aging-Related Cardiovascular Diseases

Ren, J. T., & Zhang, Y. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.10.005 · Cited by 281

Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration

Li, R., Li, D.-H., Zhang, H., Wang, J., Li, X., & Xiao, J. (2020) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0338-1 · Cited by 275

Human Aging and Longevity Are Characterized by High Levels of Mitokines

Conte, M., Ostan, R., Fabbri, C., Santoro, A., Guidarelli, G., Vitale, G., Mari, D., Sevini, F., Capri, M., Sandri, M., et al. (2019) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gly153 · Cited by 219

LncRNA: Shedding light on mechanisms and opportunities in fibrosis and aging

Yang, Z. P., Jiang, S., Shang, J., Jiang, Y., Dai, Y., Xu, B., Yu, Y., Liang, Z., & Yang, Y. (2019) · Ageing Research Reviews · doi:10.1016/j.arr.2019.04.001 · Cited by 220

Brown and Beige Adipose Tissue and Aging

Zoico, E., Rubele, S., Caro, A. D., Nori, N., Mazzali, G., Fantin, F., Rossi, A. P., & Zamboni, M. M. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00368 · Cited by 219

Integrated stress response stimulates FGF21 expression: Systemic enhancer of longevity

Salminen, A., Kaarniranta, K., & Kauppinen, A. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.08.009 · Cited by 100

FGF21 gene therapy for healthy aging: Great promise, important questions

Kuro‐o, M. (2026) · Molecular Therapy · doi:10.1016/j.ymthe.2026.07.015

FGF21 as a Stress Hormone: The Roles of FGF21 in Stress Adaptation and the Treatment of Metabolic Diseases

Kim, K. H., & Lee, M.-S. (2014) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2014.38.4.245 · Cited by 146

FGF21 connects ER stress to sulfide signaling to enhance cellular resilience

Hatem, S., Ponti, A. K., & Hine, C. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.06.009

FGF21 as a mediator of adaptive responses to stress and metabolic benefits of anti-diabetic drugs

Kim, K. H., & Lee, M. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0160 · Cited by 66