Page 77 - 83_01
P. 77
heterogeneous mice. J Gerontol A Biol Sci Med Sci Gustavo Barja de Quiroga
2011; 66: 191-201.
133. Jagannath C, Bakhru P. Rapamycin-induced
120. Wilkinson JE, Burmeister L, Brooks SV, Chan CC, enhancement of vaccine efficacy in mice. Methods
Friedline S, Harrison DE, et al. Rapamycin slows Mol Biol. 2012; 821:295-303.
aging in mice. Aging Cell 2012; 11: 675-82.
134. Richardson A, Galvan V, Lin AL, Oddo S. How
121. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle longevity research can lead to therapies for
CM, Flurkey K, et al. Rapamycin fed late in life Alzheimer´s disease: The rapamycin story. Exper
extends lifespan in genetically heterogeneous mice. Gerontol. 2015; 68: 51-8.
Nature 2009; 460: 392-5.
135. Apelo A, Pumper CP, Baar EL, Cummings NE,
122. Zhang Y, Bokov A, Gelfond J, Soto V, Ikeno Y, Lamning DW. Intermittent administration of
Hubbard G, et al. Rapamycin extends life and health rapamycin extends life span of female C57BL/6J
in C57BL/6 mice. J Gerontol A Biol Sci Med Sci mice. J Gerontol A Biol Sci Med Sci 2016; 71: 876-
2014; 69; 119-130. 81.
123. Neff F, Flores-Dominguez D, Ryan DP, Horsch M, 136. Stanfel MN, Shamieh LS, Kaeberlein M, Kennedy
Schröder S, Adler T, L.C. et al. Rapamycin extends BK. The TOR pathway comes of age. Biochim
murine lifespan but has limited effects on aging. J Biophys Acta 2009; 1790: 1067-74.
Clin Invest 2013; 123: 3272-91.
137. Kaeberlein M, Kennedy BK. Ageing: A midlife
124. Kaeberlein M, Powers RW 3rd, Steffen KK, longevity drug? Nature 2009; 460: 331-2.
Westman EA, Hu D, Dang N, et al. Regulation of
yeast replicative life span by TOR and Sch9 in 138. Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ,
response to nutrients. Science 2005; 310: 1193-6. Choudhury AI. et al. Ribosomal protein S6 kinase 1
signaling regulates mammalian life span. Science
125. Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, 2009; 326: 140-4.
Orosz L, Müller F. Genetics: influence of TOR kinase
on lifespan in C. elegans. Nature 2003; 426: 620. 139. Martínez-Cisuelo V, Gómez J, García-Junceda I,
Naudí A, Cabré R, Mota-Martorell N et al. Rapamycin
126. Schieke SM, Phillips D, McCoy JP Jr, Aponte AM, reverses age-related increases in mitochondrial ROS
Shen RF, Balaban RS et al. The mammalian target of production at complex I, oxidative stress,
rapamycin (mTOR) pathway regulates mitochondrial accumulation of mtDNA fragments inside nuclear
oxygen consumption and oxidative capacity. J Biol DNA, and lipofuscin level in liver of middle-aged
Chem 2006; 281: 27643-52. mice. Exper. Gerontol.2016; 83: 130-138.
127. McGaugh SE, Bronikowski AM, Kuo CH, Reding 140. Sato A, Nakada K , Shitara H, Kasahara A,
DM, Addis EA, Flagel LE et al. Rapid molecular Yonekawa H, Hayashi JI. Deletion-mutant mtDNA
evolution across amniotes of the IIS/TOR network. increases in somatic tissues but decreases in female
PNAS USA 2015; 112: 7055-60. germ cells with age. Genetics 2007; 177: 2031-2037.
128. Johnson SC, Yanos ME, Bitto A, Castanza A, 141. Kraytsberg Y, Kudryavtseva E, McKee AC, Geula C,
Gagnidze A, Gonzalez B, et al. Dose-dependent Kowall NW, Khrapko K. Mitochondrial DNA
effects of mTOR inhibition on weight and deletions are abundant and cause functional
mitochondrial disease in mice. Front Genet 2015; 6: impairment in aged human substantia nigra neurons.
247. Nature Genetics 2006; 38; 518-20.
129. S.C. Johnson, P.S. Rabinovitch, M. Kaeberlein, 2013. 142. Bender A, Kishnan K, Morris CM, Taylor GA, Reeve
mTOR is a key modulator of ageing and age-related AK, Perry RH, et al. High levels of mitochondrial
disease. Nature 493, 338-45. DNA deletions in substantia nigra neurons in aging
and Parkinson disease. Nat. Genet 2006; 38; 515-7.
130. Carter CS, Khamiss D, Matheny M, Toklu HZ,
Kirichenko N, Stehler KY et al. Rapamycin versus 143. Richter C. Do mitochondrial DNA fragments promote
intermittent feeding: dissociable effects on cancer and aging? FEBS Lett. 1988; 241: 1-5.
physiological and behavioral outcomes when initiated
early and late in life. J Gerontol A Biol Sci 2016; 71: 144. Suter M, Richter C. Fragmented mitochondrial DNA
865-75. is the predominant carrier of oxidized DNA bases.
Biochemistry 1999; 38: 459-64.
131. Fischer KE, Gelfond JA, Soto VY, Han C, Someya S,
Richardson A, et al. Health effects of long-term 145. Patrushev M, Kasymov V, Patrusheva V, Ushakova
rapamycin treatment: The impact on mouse health of T, Gogvadze V, Gaziev A. Mitochondrial
enteric rapamycin treatment from four months of age permeability transition triggers the release of mtDNA
throughout life. PLoS One 2015; 10:e0126644. doi: fragments. Cell Mol Life Sci 2004; 61: 3100-3.
10.1371/journal.pone.0126644.
146. Patrushev M, Kasymov V, Patrusheva V, Ushakova
132. Fisher A, Seguel JM, de la Torre AN, Wilson D, T, Gogvadze V, Gaziev AI. Release of mitochondrial
Merchant A, Arora RK, et al. Effect of sirolimus on DNA fragments from brain mitochondria of irradiated
infection incidence in liver transplant recipients. Liver mice. Mitochondrion 2006; 6: 43-7.
Transpl 2004; 10: 193-8.
147. Cheng X, Ivessa AS. The migration of mitochondrial
78 DNA fragments to the nucleus affects the
@Real Academia Nacional de Farmacia. Spain
