Abstract
The basic tenet of several theories on aging is increasing genomic instability resulting from interactions with the environment. Chromosomal aberrations have been used as classic examples of increasing genomic instability since they demonstrate an increase in numerical and structural abnormalities with age in many species including humans. This accumulating damage may augment many aging processes and initiate age-related diseases, such as neoplasias. Calorie restriction (CR) is one of the most robust interventions for reducing the frequency of age-related diseases and for extending life span in many short-lived organisms. However, the mechanisms for the anti-aging effects of CR are not yet well understood. A study of rhesus monkeys was begun in 1987 to determine if CR is also effective in reducing the frequency of age-related diseases and retarding aging in a long-lived mammal. Male monkeys were begun on the diet in 1987, and females were added in 1992 to examine a possible difference in response to CR by sex. The CR monkeys have been maintained for over 10 years on a low-fat nutritional diet that provides a 30% calorie reduction compared to a control (CON) group. Because of the greater similarity of nonhuman primates to humans in life span and environmental responses to diet compared with those of rodents, the rhesus monkey provides an excellent model for the effects of CR in humans. This study examined the effects of CR on chromosomal instability with aging. Significant age effects were found in both CR and CON groups for the number of cells with aneuploidy: old animals had a higher loss and a higher gain than young animals. However, there was no effect of age on chromosomal breakage or structural aberrations in either diet group. Diet had only one significant effect: the CR group had a higher frequency of chromatid gaps than did the CON group. CR, implemented in adult rhesus monkeys, does not have a major effect on the reduction of numerical or structural aberrations related to aging.
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References
Ames BN, Gold L, Willett WC (1995) The causes and prevention of cancer. Proc Natl Acad Sci USA 92:5258–5265
Bender MA, Preston RJ, Leonard RC, Pyatt BE, Gooch PC, Shelby MD (1988) Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. Mutat Res 204:421–433
Bender MA, Preston RJ, Leonard RC, Gooch PC, (1989) Chromosomal aberration and sister-chromatid exchange frequencies in peripheral blood lymphocytes of a large human population sample. II. Extension of age range. Mutat Res 212:149–154
Black A, Tilmont EM, Handy AM, Ingram DK, Roth GS, Lane MA (2000) Calorie restriction reduces the incidence of proliferative disease: preliminary data from the NIA CR in nonhuman primate study. Gerontologist 40, Special Issue II, p 5
Bochkov NP (1972) Spontaneous chromosome aberrations in human somatic cells. Humangenetik 16:159–164
Bodkin NL, Alexander TM, Ortmeyer HK, Johnson E, Hansen BD (2003) Morbidity and mortality in laboratory-maintained rhesus monkeys and effects of long-term dietary restriction. J Gerontol Biol Sci 58A:212–219
Bolognesi C, Abbondandolo A, Barale R, Casalone R, Dalpra L, De Ferrari M, Degrassi F, Forni A, Lamberti L, Lando C, Migliore L, Padovani P, Pasquini R, Puntoni R, Sbrana I, Stella M, Bonassi S (1997) Age-related increase of base-line frequencies of sister chromatid exchanges, chromosomal aberrations and micronuclei in human lymphocytes. Cancer Epidemiol Biomark Prev 6:249–256
Bonassi S, Abbondandolo A, Camurri L, Dalpra L, De Ferrari M, Degrassi F, Forni A, Lamberti L, Lando C, Padovani P, Sbrana I, Vecchio D, Puntoni R (1995) Are chromosome aberrations in circulating lymphocytes predictive of future cancer onset in humans? Cancer Genet Cytogenet 79:133–135
Bonassi S, Ugolini D, Kirsch-Volders, Strömberg U, Vermeulen R, Tucker JD (2005) Human population studies with cytogenetic biomarkers: review of the literature and future prospectives. Environ Mol Mutagen 45:258–270
Catalan J, Surralles J, Falck GCM, Autio K, Norppa H (2000) Segregation of sex chromosomes in human lymphocytes. Mutagenesis 15:251–255
Chessen A, Collins A (1997) Assessment of the role of diet in cancer prevention. Cancer Lett 114:237–245
Cohen MM, Levy HP (1989) Chromosome instability syndromes. Adv Hum Genet 18:42–149
Crott JW, Fenech M (1999) Effect of vitamin C supplementation on chromosome damage, apoptosis and necrosis ex vivo. Carcinogenesis 20:1035–1041
Curtis H, Crowley C (1963) Chromosome aberrations in liver cells in relation to the somatic mutation theory of aging. Radiat Res 19:337–344
DePinho RA (2000) The age of cancer. Nature 408:248–254
Evans HJ (1979) The induction of aberrations in human chromosomes following exposure to mutagens/carcinogens. In: Emmelot P, Kriek E (eds) Environmental carcinogens. Elsevier, Amsterdam, pp 57–74
Fenech M (1998) Chromosomal damage rate, aging and diet. Ann NY Acad Sci 854:23–36
Fenech M (2002) Micronutrients and genomic stability: a new paradigm for recommended dietary allowances (RDAs). Food Chem Toxicol 40:1113–1117
Fenech M, Rinaldi J (1994) The relationship between micronuclei in human lymphocytes and plasma levels of vitamin C, vitamin E, vitamin B12 and folic acid. Carcinogenesis 15:1405–1411
Fenech M, Stockley C, Aitken C (1997) Moderate wine consumption protects against hydrogen peroxide-induced DNA damage. Mutagenesis 12:289–296
Fitzgerald PH, McEwan CM (1977) Total aneuploidy and age-related sex chromosome aneuploidy in cultured lymphocytes of normal men and women. Hum Genet 39:329–337
Ford JH, Russell JA (1985) Differences in the error mechanisms affecting sex and autosomal chromosomes in women of different ages within the reproductive age group. Am J Hum Genet 37:973–983
Galloway S, Buckton K (1978) Aneuploidy and aging: chromosome studies on a random sample of the population using G-banding. Cytogenet Cell Genet 20:78–95
Galloway SM, Berry PK, Nichols WW, Wolman SR, Soper KA, Stolley PD, Archer P (1986) Chromosome aberrations in individuals occupationally exposed to ethylene oxide, and in a large control population. Mutat Res 170:55–74
Guttenbach M, Schakowski R, Schmid M (1994) Aneuploidy and ageing: sex chromosome exclusion into micronuclei. Hum Genet 94:295–298
Guttenbach M, Koschorz B, Bernthaler U, Grimm T, Schmid M (1995) Sex chromosome loss and aging: in situ hybridization studies on human interphase nuclei. Am J Hum Genet 57:1143–1150
Hagmar L, Brogger A, Hansteen I, Heim S, Hogstedt B, Knudsen L, Lambert B, Linnainmaa K, Mitelman F, Nordenson I, Reuterwall C, Salomaa S, Skerfving S, Sorsa M (1994) Cancer risk in humans predicted by increased levels of chromosomal aberrations in lymphocytes: Nordic Study Group on the health risk of chromosome damage. Cancer Res 54:2919–2922
Hando JC, Nath J, Tucker JD (1994) Sex chromosomes, micronuclei and aging in women. Chromosoma 103:186–192
Hirsch-Kauffmann M, Schweiger M (1999) Aging and chromosomal instability. Rev Physiol Biochem Pharmacol 139:141–174
Ingram DK, Cutler RG, Weindruch R, Renquist DM, Knapka JJ, April M, Belcher CT, Clark MA, Hatcherson CD, Marriott BM, Roth GS (1990) Dietary restriction and aging: the initiation of a primate study. J Gerontol 45:B148–B163
Jacobs PA, Court-Brown WM, Doll R (1961) Distribution of human chromosome counts in relation to age. Nature 191:1178–1180
Jacobs PA, Brunton M, Court-Brown WM, Doll R, Goldstein H (1963) Change in human chromosome count distributions with age: evidence for a sex difference. Nature 197:1080–1081
Jacobs PA, Brunton M, Court-Brown WM (1964) Cytogenetic studies in leucocytes on the general population: subjects 65 years or more. Ann Hum Genet 27:353–365
Lane MA, Ingram DK, Roth GS (1997) Beyond the rodent model: calorie restriction in rhesus monkeys. AGE 20:45–56
Lane MA, Mattison J, Ingram DK, Roth GS (2002) Caloric restriction and aging in primates: relevance to humans and possible CR mimetics. Microsc Res Tech 59:335–338
Lucas JN, Deng W, Moore D, Hill F, Wade M, Lewis A, Sailes F, Kramer C, Hsieh A, Galvan N (1999) Background ionizing radiation plays a minor role in the production of chromosome translocations in a control population. Int J Radiat Biol 75:819–827
Ly DH, Lockhart DJ, Lerner RA, Schultz PG (2000) Mitotic misregulation and human aging. Science 287:2486–2492
Marlhens F, Al Achkar W, Aurias A, Couturier J, Dutrillaux AM, Gerbault-Seureau M, Hoffschir F, Lamoliatte E, Lefrancois D, Lombard M, Muleris M, Prieur M, Prod’homme M, Sabatier L, Viegas-Péquignot E, Volobouev V, Dutrillaux B (1986) The rate of chromosome breakage is age dependent in lymphocytes of adult controls. Hum Genet 73:290–297
Martin GM, Ohshima J (2000) Lessons from human progeroid syndromes. Nature 408:263–266
Martin GM, Smith AC, Ketterer DJ, Ogburn CE, Disteche CM (1985) Increased chromosomal aberrations in first metaphases of cells isolated form the kidneys of aged mice. Isr J Med 21:296–301
Mattevi MS, Salzano FM (1975) Senescence and human chromosome changes. Humangenetik 27:1–8
Mattison JA, Lane MA, Roth GS, Ingram DK (2003) Calorie restriction in rhesus monkeys. Exp Gerontol 38:35–46
Maurer B, Guttenbach M, Schmid M (2003) Chromosomal instability in normative aging. In: Hisama FM, Weissman SM, Martin GM (eds) Chromosomal instability and aging. basic science and clinical implications. pp 125–147
McCay CM, Crowell MF, Maynard LA (1935) The effect of retarded growth upon the length of the lifespan and upon ultimate body size. J Nutr 10:63–79
McCullagh P, Nelder JA (1989) Generalized linear models. Chapman and Hall, New York
Moore CM, Janish C, Eddy CA, Hubbard GB, Leland MM, Rogers J (1999) Cytogenetic and fertility studies of a rheboon, rhesus macaque (Macaca mulatta) x baboon (Papio hamadryas) cross: further support for a single karyotype nomenclature. Am J Phys Anthropol 110:119–127
Nath J, Tucker JD, Hando JC (1995) Y chromosome aneuploidy, micronuclei, kinetochores and aging in men. Chromosoma 103:725–731
Nowinski GP, Van Dyke DL, Tilley BC, Jacobsen G, Babu VR, Worsham MJ, Wilson GN, Weiss L (1990) The frequency of aneuploidy in cultured lymphocytes is correlated with age and gender but not with reproductive history. Am J Hum Genet 46:1101–1111
Obe G, Herha J (1978) Chromosomal aberrations in heavy smokers. Hum Genet 41:259–263
Ortiz R, Campos C, Gómez JL, Espinoza M, Ramos-Motilla M, Betancourt M (1994) Sister-chromatid exchange (SCE) and cell proliferation in lymphocytes from infected and non-infected children with severe protein calorie malnutrition (PCM). Mutat Res 312:33–37
Pierre R, Hoagland H (1972) Age-associated aneuploidy: loss of the Y chromosome from human bone marrow cells with aging. Cancer 30:889–894
Prieur M, Achkar A, Aurias A, Couturier J, Dutrillaux A, Dutrillaux B, Flury-Herard A, Gerbault-Seureau M, Hoffschir F, Lamoliatte E, Lefrancois D, Lombard M, Muleris M, Ricoul M, Sabatier L, Viegas-Pequinot E (1988) Acquired chromosome rearrangements in human lymphocytes: effects of aging. Hum Genet 79:147–150
Ramsey MJ, Moore DH, Briner JF, Lee DA, Olsen L, Senft JR, Tucker JD (1995) The effects of age and life-style factors on the accumulation of cytogenetic damage as measured by chromosomal painting. Mutat Res 338:95–106
Richard F, Aurias A, Couturier J, Dutrillaux AM, Flüry-Hérard A, Gerbault-Seureau M, Hoffschir F, Lamoliatte E, Lefrancois D, Lombard M, Muleris M, Prieur M, Richoul M, Sabatier L, Viegas-Péquignot E, Volobouev V, Dutrillaux B (1993) Aneuploidy in human lymphocytes: an extensive study of eight individuals of various ages. Mutat Res 295:71–80
Roth GS, Ingram DK, Lane MA (1999) Calorie restriction in primates: will it work and how will we know? J Am Geriatr Soc 47:896–903
Schneider EL (1978) Cytogenetics of aging. In: Schneider EL (ed) The genetics of aging. Plenum, New York, pp 27–52
Semsei I (2000) On the nature of aging. Mech Ageing Devel 117:93–108
Solomon E, Borrow J, Goddard AD (1991) Chromosomal aberrations and cancer. Science 254:1153–1160
Stevenson KG, Curtis HJ (1961) Chromosomal aberrations in irradiated and nitrogen mustard-treated mice. Radiat Res 15:774–785
Stone JF, Sandberg AA (1995) Sex chromosome aneuploidy and aging. Mutat Res 338:107–113
Tucker JD, Lee DA, Ramsey MJ, Briner J, Olsen L, Moore II DH (1994) On the frequency of chromosome exchanges in a control population measured by chromosome painting. Mutat Res 313:193–202
Tucker JD, Spruill MD, Ramsey MJ, Director AD, Nath J (1999) Frequency of spontaneous chromosome aberrations in mice: effects of age. Mutat Res 425:135–141
Vijg J, Gossen JA (1993) Somatic mutations and cellular aging. Comp Biochem Physiol 104B:429–437
Weinberg J, Stanyon R, Jauch A, Cremer T (1992) Homologies in human and Macaca fuscata chromosomes revealed by in situ suppression hybridization with human chromosome specific libraries. Chromosoma 101:265–270
Weindruch R, Walford R (1988) The retardation of aging and disease by dietary restriction. Thomas, Springfield, IL
Weirich-Schwaiger H, Weirich HG, Gruber B, Schweiger M, Hirsch-Kauffmann M (1994) Correlation between senescence and DNA repair in cells from young and old individuals and in premature aging syndromes. Mutat Res 316:37–48
Wojda A, Witt M (2003) Manifestations of ageing at the cytogenetic level. J Appl Genet 44:383–399
Xue K, Wang S, Zhou P, Wu P, Zhang R, Xu Z, Chen W, Wang Y (1992) Micronucleus formation in peripheral blood lymphocytes from smokers and the influence of alcohol- and tea-drinking habits. Int J Cancer 50:702–705
Yu BP (1994) Modulation of aging processes by dietary restriction. CRC, Boca Raton
Acknowledgements
This study was supported in part by a grant from the National Institute on Aging. We acknowledge the excellent technical assistance of Catherine D. Weaver, B.S., and the staff at NIH, Poolesville, in particular April Hobbs and Edward Tilmont and veterinarians Drs. Doug Powell and Rick Herbert.
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Moore, C.M., Dunn, B.G., McMahan, C.A. et al. Effects of calorie restriction on chromosomal stability in rhesus monkeys (Macaca mulatta). AGE 29, 15–28 (2007). https://doi.org/10.1007/s11357-006-9016-6
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DOI: https://doi.org/10.1007/s11357-006-9016-6