Moderate caloric restriction initiated in rodents during adulthood sustains function of the female reproductive axis into advanced chronological age

Abstract

Summary Age‐related ovarian failure in women heralds the transition into postmenopausal life, which is characterized by a loss of fertility and increased risk for cardiovascular disease, osteoporosis and cognitive dysfunction. Unfortunately, there are no options available for delaying loss of ovarian function with age in humans. Rodent studies have shown that caloric restriction (CR) can extend female fertile lifespan; however, much of this work initiated CR at weaning, which causes stunted adolescent growth and a delayed onset of sexual maturation. Herein we tested in mice if CR initiated in adulthood could delay reproductive aging. After 4 months of CR, the ovarian follicle reserve was doubled compared to ad libitum (AL)‐fed age‐matched controls, which in mating trials exhibited a loss of fertility by 15.5 months of age. In CR females returned to AL feeding at 15.5 months of age, approximately one‐half remained fertile for 6 additional months and one‐third continued to deliver offspring through 23 months of age. Notably, fecundity of CR‐then‐AL‐fed females and postnatal offspring survival rates were dramatically improved compared with aging AL‐fed controls. For example, between 10 and 23 months of age, only 22% of the 54 offspring delivered by AL‐fed females survived. In contrast, over 73% of the 94 pups delivered by 15.5‐ to 23‐month‐old CR‐then‐AL‐fed mice survived without any overt complications. These data indicate that in mice adult‐onset CR maintains function of the female reproductive axis into advanced age and dramatically improves postnatal survival of offspring delivered by aged females.

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References 49

1. 1.

   Austad SN. Vertebrate aging research 2006. Aging Cell. 2007;6:135-138.

   Not in our library10.1111/j.1474-9726.2007.00280.x

2. 2.

   Ball ZB, Barnes RH, Visscher MB. The effects of dietary caloric restriction on maturity and senescence, with particular reference to fertility and longevity. Am. J. Physiol. 1947;150:511-519.

   Not in our library10.1152/ajplegacy.1947.150.3.511

3. 3.

   Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat. Rev. Drug Discov. 2006;5:493-506.

   Not in our library10.1038/nrd2060

4. 4.

   Berg BN. Nutrition and longevity in the rat. I. Food intake in relation to size, health and fertility. J. Nutr. 1960;71:242-254.

   Not in our library10.1093/jn/71.3.242

5. 5.

   Bodkin NL, Alexander TM, Ortmeyer HK, Johnson E, Hansen BC. Mortality and morbidity in laboratory-maintained rhesus monkeys and effects of long-term dietary restriction. J. Gerontol. A Biol. Sci. Med. Sci. 2003;58A:212-219.

   Not in our library10.1093/gerona/58.3.b212

6. 6.

   Buckler H. The menopause transition: endocrine changes and clinical symptoms. J. Br. Menopause Soc. 2005;11:61-65.

   Not in our library10.1258/136218005775544525

7. 7.

   Bukovsky A, Ayala ME, Dominguez R, Svetlikova M, Selleck-White R. Bone marrow derived cells and alternative pathways of oogenesis in adult rodents. Cell Cycle. 2007;6:2306-2309.

   Not in our library10.4161/cc.6.18.4707

8. 8.

   Cargill SL, Carey JR, Muller HG, Anderson G. Age of ovary determines remaining life expectancy in old ovariectomized mice. Aging Cell. 2003;2:185-190.

   Not in our library10.1046/j.1474-9728.2003.00049.x

9. 9.

   Charleston JS, Hansen KR, Thyer AC, Charleston LB, Gougeon A, Siebert JR, Soules MR, Klein NA. Estimating human ovarian non-growing follicle number: the application of modern stereology techniques to an old problem. Hum. Reprod. 2007;22:2103-2110.

   Not in our library10.1093/humrep/dem137

10. 10.

    Chen D, Guarente L. SIR2: a potential target for calorie restriction mimetics. Trends Mol. Med. 2007;13:64-71.

    Not in our library10.1016/j.molmed.2006.12.004

11. 11.

    Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum. Reprod. 1992;7:1342-1346.

    Not in our library10.1093/oxfordjournals.humrep.a137570

12. 12.

    Freret S, Grimard B, Ponter AA, Joly C, Ponsart C, Humblot P. Reduction of body-weight gain enhances in vitro embryo production in overfed superovulated dairy heifers. Reproduction. 2006;131:783-794.

    Not in our library10.1530/rep.1.00689

13. 13.

    Gonzales C, Voirol MJ, Giacomini M, Gaillard RC, Pedrazzini T, Pralong FP. The neuropeptide Y Y1 receptor mediates NPY-induced inhibition of the gonadotrope axis under poor metabolic conditions. FASEB J. 2004;18:137-139.

    Not in our library10.1096/fj.03-0189fje

14. 14.

    Gosden RG, Laing SC, Felicio LS, Nelson JF, Finch CE. Imminent oocyte exhaustion and reduced follicular recruitment mark the transition to acyclicity in aging C57BL/6J mice. Biol. Reprod. 1983;28:255-260.

    Not in our library10.1095/biolreprod28.2.255

15. 15.

    Hamilton BE, Martin JA, Ventura SJ. Births: preliminary data for 2006. Natl Vital Stat. Report. 2007;56:1-18.

    Not in our library

16. 16.

    Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA. A new model of reproductive aging: the decline in ovarian non-growing follicle number from birth to menopause. Hum. Reprod. 2008;23:699-708.

    Not in our library10.1093/humrep/dem408

17. 17.

    Holehan AM, Merry BJ. The control of puberty in the dietary restricted female rat. Mech. Ageing Dev. 1985;32:179-191.

    Not in our library10.1016/0047-6374(85)90078-8

18. 18.

    Ingram DK, Anson RM, de Cabo R, Mamczarz J, Zhu M, Mattison J, Lane MA, Roth GS. Development of calorie restriction mimetics as a prolongevity strategy. Ann. N. Y. Acad. Sci. 2004;1019:412-423.

    Not in our library10.1196/annals.1297.074

19. 19.

    Ingram DK, Roth GS, Lane MA, Ottinger MA, Zou S, de Cabo R, Mattison JA. The potential for dietary restriction to increase longevity in humans: extrapolation from monkey studies. Biogerontology. 2006;7:143-148.

    Not in our library10.1007/s10522-006-9013-2

20. 20.

    Ingram DK, Zhu M, Mamczarz J, Zou S, Lane MA, Roth GS, de Cabo R. Calorie restriction mimetics: an emerging research field. Aging Cell. 2007;5:97-108.

    Not in our library10.1111/j.1474-9726.2006.00202.x

21. 21.

    Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004;428:145-150.

    Not in our library10.1038/nature02316

22. 22.

    Johnson J, Bagley J, Skaznik-Wikiel M, Lee H-J, Adams GB, Niikura Y, Tschudy KS, Tilly JC, Cortes ML, Forkert R, Spitzer T, Iacomini J, Scadden DT, Tilly JL. Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell. 2005;122:303-315.

    Not in our library10.1016/j.cell.2005.06.031

23. 23.

    Jones PB, Krohn PL. The relationships between age, numbers of oocytes and fertility in virgin and multiparous mice. J. Endocrinol. 1961;21:469-495.

    Not in our library10.1677/joe.0.0210469

24. 24.

    Kerr JB, Myers M, Britt KL, Mladenovska T, Findlay JK. Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply. Reproduction. 2006;132:95-109.

    Not in our library10.1530/rep.1.01128

25. 25.

    van Kooij RJ, Looman CW, Habbema JD, Dorland M, te Velde ER. Age-dependent decrease in embryo implantation rate after in vitro fertilization. Fertil. Steril. 1996;66:769-775.

    Not in our library10.1016/s0015-0282(16)58634-8

26. 26.

    Lee H-J, Sakamoto H, Luo H, Skaznik-Wikiel ME, Friel A, Niikura T, Tilly JC, Klein R, Styer A, Zuckerberg L, Tilly JL, Rueda BR. Loss of CABLES1, a cyclin-dependent kinase-interacting protein that inhibits cell cycle progression, results in germline expansion at the expense of oocyte quality in adult female mice. Cell Cycle. 2007;6:2678-2684.

    Not in our library10.4161/cc.6.21.4820

27. 27.

    Lintern-Moore S, Everitt AV. The effect of restricted food intake on the size and composition of the ovarian follicle population in the Wistar rat. Biol. Reprod. 1978;19:688-691.

    Not in our library10.1095/biolreprod19.3.688

28. 28.

    Lozano JM, Lonergan P, Boland MP, O’Callaghan D. Influence of nutrition on the effectiveness of superovulation programmes in ewes: effect on oocyte quality and post-fertilization development. Reproduction. 2003;125:543-553.

    Not in our library

29. 29.

    Martin B, Golden E, Carlson OD, Egan JM, Mattson MP, Maudsley S. Caloric restriction: impact upon pituitary function and reproduction. Ageing Res. Rev. 2008.

    Not in our library10.1016/j.arr.2008.01.002

30. 30.

    Masoro EJ. Overview of caloric restriction and ageing. Mech. Ageing Dev. 2005;126:913-922.

    Not in our library10.1016/j.mad.2005.03.012

31. 31.

    Merry BJ, Holehan AM. Onset of puberty and duration of fertility in rats fed a restricted diet. J. Reprod. Fertil. 1979;57:253-259.

    Not in our library10.1530/jrf.0.0570253

32. 32.

    Navot D, Bergh PA, Williams MA, Garrisi GJ, Guzman I, Sandler B, Grunfeld L. Poor oocyte quality rather than implantation failure as a cause of age-related decline in female fertility. Lancet. 1991;337:1375-1377.

    Not in our library10.1016/0140-6736(91)93060-m

33. 33.

    Nelson JF, Gosden RG, Felicio LS. Effect of dietary restriction on estrous cyclicity and follicular reserves in aging C57BL/6J mice. Biol. Reprod. 1985;32:515-522.

    Not in our library10.1095/biolreprod32.3.515

34. 34.

    Osborne TB, Mendel LB, Ferry EL. The effect of retardation of growth upon the breeding period and duration of life of rats. Science. 1917;45:294-295.

    Not in our library10.1126/science.45.1160.294

35. 35.

    Perez GI, Robles R, Knudson CM, Flaws JA, Korsmeyer SJ, Tilly JL. Prolongation of ovarian lifespan into advanced chronological age by Bax-deficiency. Nat. Genet. 1999;21:200-203.

    Not in our library10.1038/5985

36. 36.

    Perez GI, Jurisicova A, Wise L, Lipina T, Kanisek M, Bechard A, Takai Y, Hunt P, Roder J, Grynpas M, Tilly JL. Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice. Proc. Natl Acad. Sci. USA. 2007;104:5229-5234.

    Not in our library10.1073/pnas.0608557104

37. 37.

    Richardson SJ, Senikas V, Nelson JF. Follicular depletion during the menopausal transition: evidence for accelerated loss and ultimate exhaustion. J. Clin. Endocrinol. Metab. 1987;65:1231-1237.

    Not in our library10.1210/jcem-65-6-1231

38. 38.

    Roth GS, Ingram DK, Black A, Lane MA. Effects of reduced energy intake on the biology of aging: the primate model. Eur. J. Clin. Nutr. 2000;54:S15-S20.

    Not in our library10.1038/sj.ejcn.1601020

39. 39.

    Roth GS, Mattison JA, Ottinger MA, Chachich ME, Lane MA, Ingram DK. Aging in rhesus monkeys: relevance to human health interventions. Science. 2004;305:1423-1426.

    Not in our library10.1126/science.1102541

40. 40.

    Skaznik-Wikiel M, Tilly JC, Lee H-J, Niikura Y, Kaneko-Tarui T, Johnson J, Tilly JL. Serious doubts over ‘Eggs Forever?’. Differentiation. 2007;75:93-99.

    Not in our library10.1111/j.1432-0436.2006.00117.x

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