Abstract
Impaired or deficient autophagy is believed to cause or contribute to aging, as well as several age-related pathologies. Thymic epithelial cells had a high constitutive level of autophagy. The autophagic process may play a supporting role or even a crucial role in the presentation of self-Ags in the thymus to shape the T-cell repertoires. Autophagic activity in the liver is important for the balance of energy and nutrients for basic cell functions. The abundance of autophagic structure in both cortical and medullary thymic epithelial cells and liver with mouse age has not been examined in detail. Here, we demonstrated that the architecture of mouse thymus and liver markedly changed with age. We found that the expression of LC3 detected by immunofluorescence and Western blot analysis was greatly decreased in thymus and liver of 12-month-old mice. The same level of reduction was observed in thymus and liver of 24-month-old mice. Ultrastructure analysis by an electron microscope revealed that the number of autophagic structure/vacuole in total thymic epithelial cells and hepatocytes decrease with age. The age-related decrease of autophagic structure in thymic epithelial cells may cause the reduction of immunocompetent T-cell pool in aged mice. The age-related decrease of autophagy in liver may induce accumulation of cellular materials in liver of aged mice.
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References
Bishop NA, Guarente L (2007) Genetic links between diet and lifespan: shared mechanisms from yeast to humans. Nat Rev Genet 8:835–844
Cuervo AM, Bergamini E, Brunk UT, Droge W, Ffrench M, Terman A (2005) Autophagy and aging: the importance of maintaining “clean” cells. Autophagy 1(3):131–140
Deter RL, De Duve C (1967) Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. J Cell Biol 33:437–449
Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426:895–899
Guarente L, Kenyon C (2000) Genetic pathways that regulate ageing in model organisms. Nature 408:255–262
He C, Klionsky DJ (2009) Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet 43:67–93
Hekimi S, Guarente L (2003) Genetics and the specificity of the aging process. Science 299:1351–1354
Jin S (2006) Autophagy, mitochondrial quality control, and oncogenesis. Autophagy 2:80–84
Kasai M, Tanida I, Ueno T, Kominami E, Seki S, Ikeda T, Mizuochi T (2009) Autophagic compartments gain access to the MHC class II compartments in thymic epithelium. J Immunol 183:7278–7285
Kirkwood TB, Austad SN (2000) Why do we age? Nature 408:233–238
Kyewski B, Derbinski J (2004) Self-representation in the thymus: an extended view. Nature Rev Immunol 4:688–698
Levine B, Deretic V (2007) Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7:767–777
Milićević NM, Nohroudi K, Milićević Z, Westermann J (2008) Activation of cortical and inhibited differentiation of medullary epithelial cells in the thymus of lymphotoxin-beta receptor-deficient mice: an ultrastructural study. J Anat 212(2):114–124
Mizushima N, Klionsky D (2007) Protein turnover via autophagy: implications for metabolism. Annu Rev Nutr 27:19–40
Morimoto RI (2008) Proteotoxic stress and inducible chaperone networks in neurodegenerative disease and aging. Genes Dev 22:1427–1438
Mortimore GE, Poso AR (1987) Intracellular protein catabolism and its control during nutrient deprivation and supply. Annu Rev Nutr 7:539–564
Nedjic J, Aichinger M, Emmerich J, Mizushima N, Klein L (2008) Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance. Nature 455:396–400
Rajawat YS, Bossis I (2008) Autophagy in aging and in neurodegenerative disorders. Hormones 7:46–61
Starr TK, Jameson SC, Hogquist KA (2003) Positive and negative selection of T cells. Annu Rev Immunol 21:139–176
Uddin MN, Nishio N, Ito S, Suzuki H, Isobe K (2010) Toxic effects of D-galactose on thymus and spleen that resemble aging. J Immunotoxicol 7(3):165–173
Yin XM, Ding WX, Gao W (2008) Autophagy in the liver. Hepatology 47:1773–1785
Acknowledgment
We thank Yoshikazu Fujita for technical assistance with electron microscopy and Ikuyo Mizuguchi for confocal microscopic study. This work was supported by the Ministry of Education, Science, Technology, Sports and Culture, Japan and The Hori Information Science Promotion Foundation, Japan.
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Uddin, M.N., Nishio, N., Ito, S. et al. Autophagic activity in thymus and liver during aging. AGE 34, 75–85 (2012). https://doi.org/10.1007/s11357-011-9221-9
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DOI: https://doi.org/10.1007/s11357-011-9221-9