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Erschienen in: Cancer Immunology, Immunotherapy 12/2009

01.12.2009 | Symposium in Writing

Why do centenarians escape or postpone cancer? The role of IGF-1, inflammation and p53

verfasst von: Stefano Salvioli, Miriam Capri, Laura Bucci, Cristina Lanni, Marco Racchi, Daniela Uberti, Maurizio Memo, Daniela Mari, Stefano Govoni, Claudio Franceschi

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 12/2009

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Abstract

Background

Centenarians are exceptionally long living individuals who escaped the most common age-related diseases. In particular they appear to be effectively protected from cancers. The mechanisms that underlie this protection are quite complex and still largely unclear.

Aim

To critically analyse the literature in order to propose a unifying hypothesis that can account for this cancer protection in centenarians.

Methods

Review of the scientific literature regarding three main players in tumourigenesis such as IGF-1, inflammation and p53, and centenarians.

Results

Centenarians appear to be characterised by low IGF-1-mediated responses and high levels of anti-inflammatory cytokines such as IL-10 and TGF-β, a condition that results in protection from cancer. Both inflammation and IGF-1 pathway converge on the tumour suppressor p53. Accordingly, some studies indicate that genetic variants of p53 are associated with human longevity by providing protection from cancer mortality.

Conclusions

The available data let us to hypothesise that among other possible mechanisms, well-preserved p53-mediated responses are likely a key factor contributing to protection from cancer in centenarians.
Literatur
1.
Zurück zum Zitat Franceschi C, Motta L, Motta M, Malaguarnera M, Capri M, Vasto S, Candore G, Caruso C, CE IMUS (2008) The extreme longevity: the state of the art in Italy. Exp Gerontol 43:45–52PubMedCrossRef Franceschi C, Motta L, Motta M, Malaguarnera M, Capri M, Vasto S, Candore G, Caruso C, CE IMUS (2008) The extreme longevity: the state of the art in Italy. Exp Gerontol 43:45–52PubMedCrossRef
2.
Zurück zum Zitat Caruso C, Lio D, Cavallone L, Franceschi C (2004) Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci 1028:1–13PubMedCrossRef Caruso C, Lio D, Cavallone L, Franceschi C (2004) Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci 1028:1–13PubMedCrossRef
3.
Zurück zum Zitat Piantanelli L (1988) Cancer and aging: from the kinetics of biological parameters to the kinetics of cancer incidence and mortality. Ann N Y Acad Sci 521:99–109PubMedCrossRef Piantanelli L (1988) Cancer and aging: from the kinetics of biological parameters to the kinetics of cancer incidence and mortality. Ann N Y Acad Sci 521:99–109PubMedCrossRef
4.
Zurück zum Zitat Bonafè M, Barbi C, Storci G, Salvioli S, Capri M, Olivieri F, Valensin S, Monti D, Gonos ES, De Benedictis G, Franceschi C (2002) What studies on human longevity tell us about the risk for cancer in the oldest old: data and hypotheses on the genetics and immunology of centenarians. Exp Gerontol 37:1263–1271PubMedCrossRef Bonafè M, Barbi C, Storci G, Salvioli S, Capri M, Olivieri F, Valensin S, Monti D, Gonos ES, De Benedictis G, Franceschi C (2002) What studies on human longevity tell us about the risk for cancer in the oldest old: data and hypotheses on the genetics and immunology of centenarians. Exp Gerontol 37:1263–1271PubMedCrossRef
5.
6.
Zurück zum Zitat Lanni C, Racchi M, Mazzini G, Ranzenigo A, Polotti R, Sinforiani E, Olivari L, Barcikowska M, Styczynska M, Kuznicki J, Szybinska A, Govoni S, Memo M, Uberti D (2008) Conformationally altered p53: a novel Alzheimer’s disease marker? Mol Psychiatry 13:641–647PubMedCrossRef Lanni C, Racchi M, Mazzini G, Ranzenigo A, Polotti R, Sinforiani E, Olivari L, Barcikowska M, Styczynska M, Kuznicki J, Szybinska A, Govoni S, Memo M, Uberti D (2008) Conformationally altered p53: a novel Alzheimer’s disease marker? Mol Psychiatry 13:641–647PubMedCrossRef
7.
Zurück zum Zitat Lund PK (1994) Insulin-like growth factor I: molecular biology and relevance to tissue-specific expression and action. Recent Prog Horm Res 49:125–148PubMed Lund PK (1994) Insulin-like growth factor I: molecular biology and relevance to tissue-specific expression and action. Recent Prog Horm Res 49:125–148PubMed
8.
Zurück zum Zitat Longo VD, Fabrizio P (2002) Regulation of longevity and stress resistance: a molecular strategy conserved from yeast to humans? Cell Mol Life Sci 59:903–908PubMedCrossRef Longo VD, Fabrizio P (2002) Regulation of longevity and stress resistance: a molecular strategy conserved from yeast to humans? Cell Mol Life Sci 59:903–908PubMedCrossRef
9.
Zurück zum Zitat Longo V, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299:1342–1346PubMedCrossRef Longo V, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299:1342–1346PubMedCrossRef
11.
Zurück zum Zitat Dozmorov I, Bartke A, Miller RA (2001) Array-based expression analysis of mouse liver genes: effect of age and of the longevity mutant Prop1df. J Gerontol A Biol Sci Med Sci 56:B72–B80PubMed Dozmorov I, Bartke A, Miller RA (2001) Array-based expression analysis of mouse liver genes: effect of age and of the longevity mutant Prop1df. J Gerontol A Biol Sci Med Sci 56:B72–B80PubMed
12.
Zurück zum Zitat Paolisso G, Gambardella A, Ammendola S, D’Amore A, Balbi V, Varricchio M, D’Onofrio F (1996) Glucose tolerance and insulin action in healthy centenarians. Am J Physiol 270:E890–E894PubMed Paolisso G, Gambardella A, Ammendola S, D’Amore A, Balbi V, Varricchio M, D’Onofrio F (1996) Glucose tolerance and insulin action in healthy centenarians. Am J Physiol 270:E890–E894PubMed
13.
Zurück zum Zitat Paolisso G, Barbieri M, Rizzo MR, Cartella C, Rotondi M, Bonafè M, Franceschi C, Rose G, De Benedictis G (2001) Low insulin resistance and preserved beta-cell function contribute to human longevity but are not associated with TH-INS genes. Exp Gerontol 37:149–156PubMedCrossRef Paolisso G, Barbieri M, Rizzo MR, Cartella C, Rotondi M, Bonafè M, Franceschi C, Rose G, De Benedictis G (2001) Low insulin resistance and preserved beta-cell function contribute to human longevity but are not associated with TH-INS genes. Exp Gerontol 37:149–156PubMedCrossRef
14.
Zurück zum Zitat Barbieri M, Ferrucci L, Ragno E, Corsi A, Bandinelli S, Bonafè M, Olivieri F, Giovagnetti S, Franceschi C, Guralnik JM, Paolisso G (2003) Chronic inflammation and the effect of IGF-I on muscle strength and power in older persons. Am J Physiol Endocrinol Metab 284:E481–E487PubMed Barbieri M, Ferrucci L, Ragno E, Corsi A, Bandinelli S, Bonafè M, Olivieri F, Giovagnetti S, Franceschi C, Guralnik JM, Paolisso G (2003) Chronic inflammation and the effect of IGF-I on muscle strength and power in older persons. Am J Physiol Endocrinol Metab 284:E481–E487PubMed
15.
Zurück zum Zitat Bonafè M, Barbieri M, Marchegiani F, Olivieri F, Ragno E, Giampieri C, Mugianesi E, Centurelli M, Franceschi C, Paolisso G (2003) Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab 88:3299–3304PubMedCrossRef Bonafè M, Barbieri M, Marchegiani F, Olivieri F, Ragno E, Giampieri C, Mugianesi E, Centurelli M, Franceschi C, Paolisso G (2003) Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab 88:3299–3304PubMedCrossRef
16.
Zurück zum Zitat Van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom PE, Westendorp RG (2005) Reduced insulin/IGF-1 signalling and human longevity. Aging Cell 4:79–85PubMedCrossRef Van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom PE, Westendorp RG (2005) Reduced insulin/IGF-1 signalling and human longevity. Aging Cell 4:79–85PubMedCrossRef
17.
Zurück zum Zitat Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 105:3438–3442PubMedCrossRef Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 105:3438–3442PubMedCrossRef
18.
Zurück zum Zitat Cappola AR, Xuem QL, Ferrucci L, Guralnik JM, Volpato S, Fried LP (2003) Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab 88:2019–2025PubMedCrossRef Cappola AR, Xuem QL, Ferrucci L, Guralnik JM, Volpato S, Fried LP (2003) Insulin-like growth factor I and interleukin-6 contribute synergistically to disability and mortality in older women. J Clin Endocrinol Metab 88:2019–2025PubMedCrossRef
19.
Zurück zum Zitat Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363:1346–1353PubMedCrossRef Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363:1346–1353PubMedCrossRef
20.
Zurück zum Zitat Baserga R, Peruzzi F, Reiss K (2003) The IGF-1 receptor in cancer biology. Int J Cancer 107:873–877PubMedCrossRef Baserga R, Peruzzi F, Reiss K (2003) The IGF-1 receptor in cancer biology. Int J Cancer 107:873–877PubMedCrossRef
21.
Zurück zum Zitat Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, Odijk H, Oostendorp R, Ahmad A, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GT, Meinecke P, Kleijer WJ, Vijg J, Jaspers NG, Hoeijmakers JH (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444:1038–1043PubMedCrossRef Niedernhofer LJ, Garinis GA, Raams A, Lalai AS, Robinson AR, Appeldoorn E, Odijk H, Oostendorp R, Ahmad A, van Leeuwen W, Theil AF, Vermeulen W, van der Horst GT, Meinecke P, Kleijer WJ, Vijg J, Jaspers NG, Hoeijmakers JH (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444:1038–1043PubMedCrossRef
22.
Zurück zum Zitat Schumacher B, van der Pluijm I, Moorhouse MJ, Kosteas T, Robinson AR, Suh Y, Breit TM, van Steeg H, Niedernhofer LJ, van Ijcken W, Bartke A, Spindler SR, Hoeijmakers JH, van der Horst GT, Garinis GA (2008) Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet 4:e1000161PubMedCrossRef Schumacher B, van der Pluijm I, Moorhouse MJ, Kosteas T, Robinson AR, Suh Y, Breit TM, van Steeg H, Niedernhofer LJ, van Ijcken W, Bartke A, Spindler SR, Hoeijmakers JH, van der Horst GT, Garinis GA (2008) Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet 4:e1000161PubMedCrossRef
23.
Zurück zum Zitat Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444PubMedCrossRef Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444PubMedCrossRef
24.
Zurück zum Zitat Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254 Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254
25.
Zurück zum Zitat Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevità emerged from studies in humans. Mech Ageing Dev 128:92–105PubMedCrossRef Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevità emerged from studies in humans. Mech Ageing Dev 128:92–105PubMedCrossRef
26.
Zurück zum Zitat Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafé M, Cavallone L, Marchegiani F, Olivieri F, Franceschi C, Caruso C (2003) Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10–1082 promoter SNP and its interaction with TNF-alpha -308 promoter SNP. J Med Genet 40:296–299PubMedCrossRef Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafé M, Cavallone L, Marchegiani F, Olivieri F, Franceschi C, Caruso C (2003) Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10–1082 promoter SNP and its interaction with TNF-alpha -308 promoter SNP. J Med Genet 40:296–299PubMedCrossRef
27.
Zurück zum Zitat Cavallone L, Bonafè M, Olivieri F, Cardelli M, Marchegiani F, Giovagnetti S, Di Stasio G, Giampieri C, Mugianesi E, Stecconi R, Sciacca F, Grimaldi LM, De Benedictis G, Lio D, Caruso C, Franceschi C (2003) The role of IL-1 gene cluster in longevity: a study in Italian population. Mech Ageing Dev 124:533–538PubMedCrossRef Cavallone L, Bonafè M, Olivieri F, Cardelli M, Marchegiani F, Giovagnetti S, Di Stasio G, Giampieri C, Mugianesi E, Stecconi R, Sciacca F, Grimaldi LM, De Benedictis G, Lio D, Caruso C, Franceschi C (2003) The role of IL-1 gene cluster in longevity: a study in Italian population. Mech Ageing Dev 124:533–538PubMedCrossRef
28.
Zurück zum Zitat Carrieri G, Marzi E, Olivieri F, Marchegiani F, Cavallone L, Cardelli M, Giovagnetti S, Stecconi R, Molendini C, Trapassi C, De Benedictis G, Kletsas D, Franceschi C (2004) The G/C915 polymorphism of transforming growth factor beta1 is associated with human longevity: a study in Italian centenarians. Aging Cell 3:443–448PubMedCrossRef Carrieri G, Marzi E, Olivieri F, Marchegiani F, Cavallone L, Cardelli M, Giovagnetti S, Stecconi R, Molendini C, Trapassi C, De Benedictis G, Kletsas D, Franceschi C (2004) The G/C915 polymorphism of transforming growth factor beta1 is associated with human longevity: a study in Italian centenarians. Aging Cell 3:443–448PubMedCrossRef
29.
Zurück zum Zitat Mannucci PM, Mari D, Merati G, Peyvandi F, Tagliabue L, Sacchi E, Taioli E, Sansoni P, Bertolini S, Franceschi C (1997) Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins. A study in centenarians. Arterioscler Thromb Vasc Biol 17:755–759PubMed Mannucci PM, Mari D, Merati G, Peyvandi F, Tagliabue L, Sacchi E, Taioli E, Sansoni P, Bertolini S, Franceschi C (1997) Gene polymorphisms predicting high plasma levels of coagulation and fibrinolysis proteins. A study in centenarians. Arterioscler Thromb Vasc Biol 17:755–759PubMed
30.
Zurück zum Zitat Kortlever RM, Higgins PJ, Bernards R (2006) Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat Cell Biol 8:877–884PubMedCrossRef Kortlever RM, Higgins PJ, Bernards R (2006) Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat Cell Biol 8:877–884PubMedCrossRef
31.
Zurück zum Zitat Franceschi C, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Capri M, Salvioli S, Valensin S, De Benedictis G, Di Iorio A, Caruso C, Paolisso G, Monti D (2005) Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev 126:351–361PubMedCrossRef Franceschi C, Olivieri F, Marchegiani F, Cardelli M, Cavallone L, Capri M, Salvioli S, Valensin S, De Benedictis G, Di Iorio A, Caruso C, Paolisso G, Monti D (2005) Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians. Mech Ageing Dev 126:351–361PubMedCrossRef
32.
Zurück zum Zitat Bonafè M, Olivieri F, Cavallone L, Giovagnetti S, Mayegiani F, Cardelli M, Pieri C, Marra M, Antonicelli R, Lisa R, Rizzo MR, Paolisso G, Monti D, Franceschi C (2001) A gender—dependent genetic predisposition to produce high levels of IL–6 is detrimental for longevity. Eur J Immunol 31:2357–2361PubMedCrossRef Bonafè M, Olivieri F, Cavallone L, Giovagnetti S, Mayegiani F, Cardelli M, Pieri C, Marra M, Antonicelli R, Lisa R, Rizzo MR, Paolisso G, Monti D, Franceschi C (2001) A gender—dependent genetic predisposition to produce high levels of IL–6 is detrimental for longevity. Eur J Immunol 31:2357–2361PubMedCrossRef
33.
Zurück zum Zitat Cardelli M, Cavallone L, Marchegiani F, Oliveri F, Dato S, Montesanto A, Lescai F, Lisa R, De Benedictis G, Franceschi C (2008) A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism. J Gerontol A Biol Sci Med Sci 63:454–460PubMed Cardelli M, Cavallone L, Marchegiani F, Oliveri F, Dato S, Montesanto A, Lescai F, Lisa R, De Benedictis G, Franceschi C (2008) A genetic-demographic approach reveals male-specific association between survival and tumor necrosis factor (A/G)-308 polymorphism. J Gerontol A Biol Sci Med Sci 63:454–460PubMed
34.
Zurück zum Zitat Belluco C, Olivieri F, Bonafè M, Giovagnetti S, Mammano E, Scalerta R, Ambrosi A, Franceschi C, Nitti D, Lise M (2003) 174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res 9:2173–2176PubMed Belluco C, Olivieri F, Bonafè M, Giovagnetti S, Mammano E, Scalerta R, Ambrosi A, Franceschi C, Nitti D, Lise M (2003) 174 G>C polymorphism of interleukin 6 gene promoter affects interleukin 6 serum level in patients with colorectal cancer. Clin Cancer Res 9:2173–2176PubMed
35.
Zurück zum Zitat Ancrile B, Lim KH, Counter CM (2007) Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 21:1714–1719PubMedCrossRef Ancrile B, Lim KH, Counter CM (2007) Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis. Genes Dev 21:1714–1719PubMedCrossRef
36.
Zurück zum Zitat Sansone P, Storci G, Tavolari S, Guarnieri T, Giovannini C, Taffurelli M, Ceccarelli C, Santini D, Paterini P, Marcu KB, Chieco P, Bonafè M (2007) IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 117:3988–4002PubMedCrossRef Sansone P, Storci G, Tavolari S, Guarnieri T, Giovannini C, Taffurelli M, Ceccarelli C, Santini D, Paterini P, Marcu KB, Chieco P, Bonafè M (2007) IL-6 triggers malignant features in mammospheres from human ductal breast carcinoma and normal mammary gland. J Clin Invest 117:3988–4002PubMedCrossRef
37.
Zurück zum Zitat Hodge DR, Peng B, Cherry JC, Hurt EM, Fox SD, Kelley JA, Munroe DJ, Farrar WL (2005) Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation. Cancer Res 65:4673–4682PubMedCrossRef Hodge DR, Peng B, Cherry JC, Hurt EM, Fox SD, Kelley JA, Munroe DJ, Farrar WL (2005) Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation. Cancer Res 65:4673–4682PubMedCrossRef
38.
Zurück zum Zitat Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ, Aarden LA, Mooi WJ, Peeper DS (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133:1019–1031PubMedCrossRef Kuilman T, Michaloglou C, Vredeveld LC, Douma S, van Doorn R, Desmet CJ, Aarden LA, Mooi WJ, Peeper DS (2008) Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network. Cell 133:1019–1031PubMedCrossRef
39.
Zurück zum Zitat Dijsselbloem N, Goriely S, Albarani V, Gerlo S, Francoz S, Marine JC, Goldman M, Haegeman G, Vanden Berghe W (2007) A critical role for p53 in the control of NF-kappaB-dependent gene expression in TLR4-stimulated dendritic cells exposed to Genistein. J Immunol 178:5048–5057PubMed Dijsselbloem N, Goriely S, Albarani V, Gerlo S, Francoz S, Marine JC, Goldman M, Haegeman G, Vanden Berghe W (2007) A critical role for p53 in the control of NF-kappaB-dependent gene expression in TLR4-stimulated dendritic cells exposed to Genistein. J Immunol 178:5048–5057PubMed
41.
42.
Zurück zum Zitat Attardi LD, Donehower LA (2005) Probing p53 biological functions through the use of genetically engineered mouse models. Mutat Res 576:4–21PubMed Attardi LD, Donehower LA (2005) Probing p53 biological functions through the use of genetically engineered mouse models. Mutat Res 576:4–21PubMed
43.
Zurück zum Zitat Scrable H, Medrano S, Ungewitter E (2008) Running on empty: how p53 controls INS/IGF signaling and affects lifespan. Exp Gerontol [Epub ahead of print] Scrable H, Medrano S, Ungewitter E (2008) Running on empty: how p53 controls INS/IGF signaling and affects lifespan. Exp Gerontol [Epub ahead of print]
44.
Zurück zum Zitat Staib F, Robles AI, Varticovski L, Wang XW, Zeeberg BR, Sirotin M, Zhurkin VB, Hofseth LJ, Hussain SP, Weinstein JN, Galle PR, Harris CC (2005) The p53 tumor suppressor network is a key responder to microenvironmental components of chronic inflammatory stress. Cancer Res 65:10255–10264PubMedCrossRef Staib F, Robles AI, Varticovski L, Wang XW, Zeeberg BR, Sirotin M, Zhurkin VB, Hofseth LJ, Hussain SP, Weinstein JN, Galle PR, Harris CC (2005) The p53 tumor suppressor network is a key responder to microenvironmental components of chronic inflammatory stress. Cancer Res 65:10255–10264PubMedCrossRef
45.
46.
Zurück zum Zitat Zhao R, Gish K, Murphy M, Yin Y, Notterman D, Hoffman WH, Tom E, Mack DH, Levine AJ (2000) Analysis of p53- regulated gene expression patterns using oligonucleotide arrays. Genes Dev 14:981–993PubMedCrossRef Zhao R, Gish K, Murphy M, Yin Y, Notterman D, Hoffman WH, Tom E, Mack DH, Levine AJ (2000) Analysis of p53- regulated gene expression patterns using oligonucleotide arrays. Genes Dev 14:981–993PubMedCrossRef
47.
Zurück zum Zitat Wang L, Wu Q, Qiu P, Mirza A, McGuirk M, Kirschmeier P, Greene JR, Wang Y, Pickett CB, Liu S (2001) Analyses of p53 target genes in the human genome by bioinformatic and microarray approaches. J Biol Chem 276:43604–43610PubMedCrossRef Wang L, Wu Q, Qiu P, Mirza A, McGuirk M, Kirschmeier P, Greene JR, Wang Y, Pickett CB, Liu S (2001) Analyses of p53 target genes in the human genome by bioinformatic and microarray approaches. J Biol Chem 276:43604–43610PubMedCrossRef
48.
Zurück zum Zitat Leech M, Xue JR, Dacumos A, Hall P, Santos L, Yang Y, Li M, Kitching AR, Morand EF (2008) The tumour suppressor gene p53 modulates the severity of antigen-induced arthritis and the systemic immune response. Clin Exp Immunol 152:345–353PubMedCrossRef Leech M, Xue JR, Dacumos A, Hall P, Santos L, Yang Y, Li M, Kitching AR, Morand EF (2008) The tumour suppressor gene p53 modulates the severity of antigen-induced arthritis and the systemic immune response. Clin Exp Immunol 152:345–353PubMedCrossRef
49.
Zurück zum Zitat Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221PubMedCrossRef Donehower LA, Harvey M, Slagle BL, McArthur MJ, Montgomery CA Jr, Butel JS, Bradley A (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356:215–221PubMedCrossRef
50.
Zurück zum Zitat Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Hee Park S, Thompson T, Karsenty G, Bradley A, Donehower LA (2002) p53 Mutant mice that display early ageing-associated phenotypes. Nature 415:45–53PubMedCrossRef Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Hee Park S, Thompson T, Karsenty G, Bradley A, Donehower LA (2002) p53 Mutant mice that display early ageing-associated phenotypes. Nature 415:45–53PubMedCrossRef
52.
Zurück zum Zitat Moore L, Lu X, Ghebranious N, Tyner S, Donehower LA (2007) Aging-associated truncated form of p53 interacts with wild-type p53 and alters p53 stability, localization, and activity. Mech Ageing Dev 128:717–730PubMedCrossRef Moore L, Lu X, Ghebranious N, Tyner S, Donehower LA (2007) Aging-associated truncated form of p53 interacts with wild-type p53 and alters p53 stability, localization, and activity. Mech Ageing Dev 128:717–730PubMedCrossRef
53.
Zurück zum Zitat García-Cao I, García-Cao M, Martín-Caballero J, Criado LM, Klatt P, Flores JM, Weill JC, Blasco MA, Serrano M (2002) “Super p53” mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J 21:6225–6235PubMedCrossRef García-Cao I, García-Cao M, Martín-Caballero J, Criado LM, Klatt P, Flores JM, Weill JC, Blasco MA, Serrano M (2002) “Super p53” mice exhibit enhanced DNA damage response, are tumor resistant and age normally. EMBO J 21:6225–6235PubMedCrossRef
54.
Zurück zum Zitat Matheu A, Maraver A, Klatt P, Flores I, Garcia-Cao I, Borras C, Flores JM, Viña J, Blasco MA, Serrano M (2007) Delayed ageing through damage protection by the Arf/p53 pathway. Nature 448:375–379PubMedCrossRef Matheu A, Maraver A, Klatt P, Flores I, Garcia-Cao I, Borras C, Flores JM, Viña J, Blasco MA, Serrano M (2007) Delayed ageing through damage protection by the Arf/p53 pathway. Nature 448:375–379PubMedCrossRef
55.
Zurück zum Zitat Feng Z, Hu W, Teresky AK, Hernando E, Cordon-Cardo C, Levine AJ (2007) Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations. Proc Natl Acad Sci USA 104:16633–16638PubMedCrossRef Feng Z, Hu W, Teresky AK, Hernando E, Cordon-Cardo C, Levine AJ (2007) Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations. Proc Natl Acad Sci USA 104:16633–16638PubMedCrossRef
56.
Zurück zum Zitat Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y, Shkedy D (1999) Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc Natl Acad Sci USA 96:14973–14977PubMedCrossRef Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y, Shkedy D (1999) Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc Natl Acad Sci USA 96:14973–14977PubMedCrossRef
57.
Zurück zum Zitat Méplan C, Richard MJ, Hainaut P (2000) Redox signalling and transition metals in the control of the p53 pathway. Biochem Pharmacol 59:25–33PubMedCrossRef Méplan C, Richard MJ, Hainaut P (2000) Redox signalling and transition metals in the control of the p53 pathway. Biochem Pharmacol 59:25–33PubMedCrossRef
58.
Zurück zum Zitat Uberti D, Lanni C, Carsana T, Francisconi S, Missale C, Racchi M, Govoni S, Memo M (2006) Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer’s disease patients. Neurobiol Aging 27:1193–1201PubMedCrossRef Uberti D, Lanni C, Carsana T, Francisconi S, Missale C, Racchi M, Govoni S, Memo M (2006) Identification of a mutant-like conformation of p53 in fibroblasts from sporadic Alzheimer’s disease patients. Neurobiol Aging 27:1193–1201PubMedCrossRef
59.
Zurück zum Zitat Uberti D, Carsana T, Bernardi E, Rodella L, Grigolato P, Lanni C, Racchi M, Govoni S, Memo M (2002) Selective impairment of p53-mediated cell death in fibroblasts from sporadic Alzheimer’s disease patients. J Cell Sci 115:3131–3138PubMed Uberti D, Carsana T, Bernardi E, Rodella L, Grigolato P, Lanni C, Racchi M, Govoni S, Memo M (2002) Selective impairment of p53-mediated cell death in fibroblasts from sporadic Alzheimer’s disease patients. J Cell Sci 115:3131–3138PubMed
60.
Zurück zum Zitat Roe CM, Behrens MI, Xiong C, Miller JP, Morris JC (2005) Alzheimer disease and cancer. Neurology 64:895–898PubMed Roe CM, Behrens MI, Xiong C, Miller JP, Morris JC (2005) Alzheimer disease and cancer. Neurology 64:895–898PubMed
61.
Zurück zum Zitat Lanni C, Uberti D, Racchi M, Govoni S, Memo M (2007) Unfolded p53: a potential biomarker for Alzheimer’s disease. J Alzheimers Dis 12:93–99PubMed Lanni C, Uberti D, Racchi M, Govoni S, Memo M (2007) Unfolded p53: a potential biomarker for Alzheimer’s disease. J Alzheimers Dis 12:93–99PubMed
62.
Zurück zum Zitat Maier B, Gluba W, Bernier B, Turner T, Mohammad K, Guise T, Sutherland A, Thorner M, Scrable H (2004) Modulation of mammalian life span by the short isoform of p53. Genes Dev 18:306–319PubMedCrossRef Maier B, Gluba W, Bernier B, Turner T, Mohammad K, Guise T, Sutherland A, Thorner M, Scrable H (2004) Modulation of mammalian life span by the short isoform of p53. Genes Dev 18:306–319PubMedCrossRef
63.
Zurück zum Zitat Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, Saville MK, Lane DP (2005) p53 Isoforms can regulate p53 transcriptional activity. Genes Dev 19:2122–2137PubMedCrossRef Bourdon JC, Fernandes K, Murray-Zmijewski F, Liu G, Diot A, Xirodimas DP, Saville MK, Lane DP (2005) p53 Isoforms can regulate p53 transcriptional activity. Genes Dev 19:2122–2137PubMedCrossRef
65.
Zurück zum Zitat Van Heemst D, Mooijaart SP, Beekman M, Schreuder J, de Craen AJ, Brandt BW, Slagboom PE, Westendorp RG, Group LongLifeStudy (2005) Variation in the human TP53 gene affects old age survival and cancer mortality. Exp Gerontol 40:11–15PubMedCrossRef Van Heemst D, Mooijaart SP, Beekman M, Schreuder J, de Craen AJ, Brandt BW, Slagboom PE, Westendorp RG, Group LongLifeStudy (2005) Variation in the human TP53 gene affects old age survival and cancer mortality. Exp Gerontol 40:11–15PubMedCrossRef
66.
Zurück zum Zitat Mammano E, Belluco C, Bonafé M, Olivieri F, Mugianesi E, Barbi C, Mishto M, Cosci M, Franceschi C, Lise M, Nitti D (2008) Association of p53 polymorphisms and colorectal cancer: modulation of risk and progression. Eur J Surg Oncol (Epub ahead of print) Mammano E, Belluco C, Bonafé M, Olivieri F, Mugianesi E, Barbi C, Mishto M, Cosci M, Franceschi C, Lise M, Nitti D (2008) Association of p53 polymorphisms and colorectal cancer: modulation of risk and progression. Eur J Surg Oncol (Epub ahead of print)
67.
Zurück zum Zitat Ørsted DD, Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG (2007) Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population. J Exp Med 204:1295–1301PubMedCrossRef Ørsted DD, Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG (2007) Tumor suppressor p53 Arg72Pro polymorphism and longevity, cancer survival, and risk of cancer in the general population. J Exp Med 204:1295–1301PubMedCrossRef
68.
Zurück zum Zitat Regula KM, Kirshenbaum LA (2001) p53 Activates the mitochondrial death pathway and apoptosis of ventricular myocytes independent of de novo gene transcription. J Mol Cell Cardiol 33:1435–1445PubMedCrossRef Regula KM, Kirshenbaum LA (2001) p53 Activates the mitochondrial death pathway and apoptosis of ventricular myocytes independent of de novo gene transcription. J Mol Cell Cardiol 33:1435–1445PubMedCrossRef
69.
Zurück zum Zitat Bonafé M, Salvioli S, Barbi C, Trapassi C, Tocco F, Storci G, Invidia L, Vannini I, Rossi M, Marzi E, Mishto M, Capri M, Olivieri F, Antonicelli R, Memo M, Uberti D, Nacmias B, Sorbi S, Monti D, Franceschi C (2004) The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death. Cell Death Differ 11:962–973PubMedCrossRef Bonafé M, Salvioli S, Barbi C, Trapassi C, Tocco F, Storci G, Invidia L, Vannini I, Rossi M, Marzi E, Mishto M, Capri M, Olivieri F, Antonicelli R, Memo M, Uberti D, Nacmias B, Sorbi S, Monti D, Franceschi C (2004) The different apoptotic potential of the p53 codon 72 alleles increases with age and modulates in vivo ischaemia-induced cell death. Cell Death Differ 11:962–973PubMedCrossRef
70.
Zurück zum Zitat Salvioli S, Bonafé M, Barbi C, Storci G, Trapassi C, Tocco F, Gravina S, Rossi M, Tiberi L, Mondello C, Monti D, Franceschi C (2005) p53 Codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21WAF1. Cell Cycle 4:1264–1271PubMed Salvioli S, Bonafé M, Barbi C, Storci G, Trapassi C, Tocco F, Gravina S, Rossi M, Tiberi L, Mondello C, Monti D, Franceschi C (2005) p53 Codon 72 alleles influence the response to anticancer drugs in cells from aged people by regulating the cell cycle inhibitor p21WAF1. Cell Cycle 4:1264–1271PubMed
Metadaten
Titel
Why do centenarians escape or postpone cancer? The role of IGF-1, inflammation and p53
verfasst von
Stefano Salvioli
Miriam Capri
Laura Bucci
Cristina Lanni
Marco Racchi
Daniela Uberti
Maurizio Memo
Daniela Mari
Stefano Govoni
Claudio Franceschi
Publikationsdatum
01.12.2009
Verlag
Springer-Verlag
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 12/2009
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-008-0639-6

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