Anat Cell Biol.  2015 Mar;48(1):54-61. 10.5115/acb.2015.48.1.54.

Expression of SIRT1 and SIRT3 varies according to age in mice

• Kwon Y
• Kim J
• Lee CY
• Kim H

• KMID: 2046075
• DOI: http://doi.org/10.5115/acb.2015.48.1.54

Abstract

Sirtuins (SIRTs) are involved in multiple cellular processes including those related to aging, cancer, and a variety of cellular functions including cell cycle progression, DNA repair, and cellular proliferation. SIRTs have been shown to extend the yeast life span, although there is presently little known about SIRT expression in the organs of mice. In the present study, we were especially interested in identifying differences in SIRT expression between young mice and aged mice. Specifically, we investigated the expression of SIRT1 and SIRT3 in the kidney, lung, skin, adipose tissue, and spleens of 6-month-old and 24-month-old mice using immunohistochemical staining. Compared with that in younger mice, the expression of SIRT1 in 24-month-old rats was increased in kidney, lung, and spleen tissue, while that of SIRT3 was decreased in adipose, kidney, and lung tissue. The results of our study suggest that aging is associated with altered patterns of expression of SIRT1 and SIRT3. In addition, we noted that the expression patterns of SIRT1 and SIRT3 varied by organ. Taken together, the results of this study suggest the possibility that SIRTs may be involved in diseases associated with aging.

Keyword

Sirtuin1; Sirtuin3; Immunohistochemistry; Aging

MeSH Terms

Adipose Tissue
Aging
Animals
Cell Cycle
Cell Proliferation
Child, Preschool
DNA Repair
Humans
Immunohistochemistry
Infant
Kidney
Lung
Mice*
Rats
Sirtuins
Skin
Spleen
Yeasts
Sirtuins

Figure

• 

  Fig. 1 Representative immunohistochemical micrographs of adipose tissue (A, B), kidney (C, D), spleen (E, F), skin (G, H), lung (I, J), and liver (K, L). Immunoreactivity of SIRT1 in 6-month-old rat (left column) as compared of 2-year-old rat (right column). Scale bars=100 µm (A-L).

• 

  Fig. 2 Representative immunohistochemical micrographs of adipose tissue (A, B), kidney (C, D), spleen (E, F), skin (G, H), lung (I, J), and liver (K, L). Immunoreactivity of SIRT3 in 6-month-old rat (left column) as compared of 2-year-old rat (right column). Scale bars=100 µm (A-L).

Reference

1. Sebastian C, Satterstrom FK, Haigis MC, Mostoslavsky R. From sirtuin biology to human diseases: an update. J Biol Chem. 2012; 287:42444–42452.

2. Kaeberlein M, McVey M, Guarente L. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999; 13:2570–2580.

3. Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012; 13:225–238.

4. Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA. Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell. 2010; 143:802–812.

5. Qiu X, Brown K, Hirschey MD, Verdin E, Chen D. Calorie restriction reduces oxidative stress by SIRT3-mediated SOD2 activation. Cell Metab. 2010; 12:662–667.

6. Tao R, Coleman MC, Pennington JD, Ozden O, Park SH, Jiang H, Kim HS, Flynn CR, Hill S, Hayes McDonald W, Olivier AK, Spitz DR, Gius D. Sirt3-mediated deacetylation of evolutionarily conserved lysine 122 regulates MnSOD activity in response to stress. Mol Cell. 2010; 40:893–904.

7. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, Bar-Joseph Z, Cohen HY. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012; 483:218–221.

8. Sebastian C, Zwaans BM, Silberman DM, Gymrek M, Goren A, Zhong L, Ram O, Truelove J, Guimaraes AR, Toiber D, Cosentino C, Greenson JK, MacDonald AI, McGlynn L, Maxwell F, Edwards J, Giacosa S, Guccione E, Weissleder R, Bernstein BE, Regev A, Shiels PG, Lombard DB, Mostoslavsky R. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell. 2012; 151:1185–1199.

9. Chen X, Hokka D, Maniwa Y, Ohbayashi C, Itoh T, Hayashi Y. Sirt1 is a tumor promoter in lung adenocarcinoma. Oncol Lett. 2014; 8:387–393.

10. Xiao K, Jiang J, Wang W, Cao S, Zhu L, Zeng H, Ouyang R, Zhou R, Chen P. Sirt3 is a tumor suppressor in lung adenocarcinoma cells. Oncol Rep. 2013; 30:1323–1328.

11. Fan H, Yang HC, You L, Wang YY, He WJ, Hao CM. The histone deacetylase, SIRT1, contributes to the resistance of young mice to ischemia/reperfusion-induced acute kidney injury. Kidney Int. 2013; 83:404–413.

12. Funk JA, Schnellmann RG. Accelerated recovery of renal mitochondrial and tubule homeostasis with SIRT1/PGC-1alpha activation following ischemia-reperfusion injury. Toxicol Appl Pharmacol. 2013; 273:345–354.

13. Kitada M, Kume S, Takeda-Watanabe A, Kanasaki K, Koya D. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy. Clin Sci (Lond). 2013; 124:153–164.

14. Kong S, McBurney MW, Fang D. Sirtuin 1 in immune regulation and autoimmunity. Immunol Cell Biol. 2012; 90:6–13.

15. Moschen AR, Wieser V, Gerner RR, Bichler A, Enrich B, Moser P, Ebenbichler CF, Kaser S, Tilg H. Adipose tissue and liver expression of SIRT1, 3, and 6 increase after extensive weight loss in morbid obesity. J Hepatol. 2013; 59:1315–1322.

16. Cao C, Lu S, Kivlin R, Wallin B, Card E, Bagdasarian A, Tamakloe T, Wang WJ, Song X, Chu WM, Kouttab N, Xu A, Wan Y. SIRT1 confers protection against UVB- and H2O2-induced cell death via modulation of p53 and JNK in cultured skin keratinocytes. J Cell Mol Med. 2009; 13:3632–3643.