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Diet restriction and ageing in the dog: major observations over two decades

  • Dennis F. Lawler (a1), Brian T. Larson (a1), Joan M. Ballam (a1), Gail K. Smith (a2), Darryl N. Biery (a2), Richard H. Evans (a3), Elizabeth H. Greeley (a4), Mariangela Segre (a4), Howard D. Stowe (a5) and Richard D. Kealy (a1)...


This report reviews decade two of the lifetime diet restriction study of the dog. Labrador retrievers (n 48) were paired at age 6 weeks by sex and weight within each of seven litters, and assigned randomly within the pair to control-feeding (CF) or 25 % diet restriction (DR). Feeding began at age 8 weeks. The same diet was fed to all dogs; only the quantity differed. Major lifetime observations included 1·8 years longer median lifespan among diet-restricted dogs, with delayed onset of late life diseases, especially osteoarthritis. Long-term DR did not negatively affect skeletal maturation, structure or metabolism. Among all dogs, high static fat mass and declining lean body mass predicted death, most strongly at 1 year prior. Fat mass above 25 % was associated with increasing insulin resistance, which independently predicted lifespan and chronic diseases. Metabolizable energy requirement/lean body mass most accurately explained energy metabolism due to diet restriction; diet-restricted dogs required 17 % less energy to maintain each lean kilogram. Metabonomics-based urine metabolite trajectories reflected DR-related differences, suggesting that signals from gut microbiota may be involved in the DR longevity and health responses. Independent of feeding group, increased hazard of earlier death was associated with lower lymphoproliferative responses to phytohaemagglutinin, concanavalin A, and pokeweed mitogen; lower total lymphocytes, T-cells, CD4 and CD8 cells; lower CD8 percentages and higher B-cell percentages. When diet group was taken into account, PWM responses and cell counts and percentages remained predictive of earlier death.

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Corresponding author

*Dr Dennis F. Lawler, fax +1314 982 5857, email


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1 Kealy, RD, Olsson, S-E, Monti, KL, Lawler, DF, Biery, DN, Helms, RW, Lust, G & Smith, G (1992) Effects of limited food consumption on the incidence of hip dysplasia in growing dogs. J Am Vet Med Assoc 201, 857863.
2 Kealy, RD, Lawler, DF, Ballam, JM, Lust, G, Smith, GK, Biery, DN & Olsson, S-E (1997) Five-year longitudinal study on limited food consumption and development of osteoarthritis in coxofemoral joints of dogs. J Am Vet Med Assoc 210, 222225.
3 Kealy, RD, Lawler, DF, Ballam, JM, Mantz, SL, Biery, DN, Greeley, EH, Lust, G, Segre, M, Smith, GK & Stowe, HD (2002) Effects of diet restriction on life span and age-related changes in dogs. J Am Vet Med Assoc 220, 13151320.
4 Lawler, DF, Evans, RH, Larson, BT, Spitznagel, EL, Ellersieck, MR & Kealy, RD (2005) Influence of lifetime food restriction on causes, time, and predictors of death in dogs. J Am Vet Med Assoc 226, 225231.
5 Wang, C, Weindruch, R, Fernandez, JR, Coffey, CS, Patel, P & Allison, DB (2004) Caloric restriction and body weight independently affect longevity in Wistar rats. Int J Obes 28, 357362.
6 Barzilai, N & Bupta, G (1999) Revisiting the role of fat mass in the life extension induced by caloric restriction. J Gerontol 3, B89B96.
7 Harrison, DE, Archer, JR & Astle, CM (1984) Effects of food restriction on aging. Separation of food intake and adiposity. Proc Natl Acad Sci U S A 81, 18351838.
8 Larson, BT, Lawler, DF, Spitznagel, EL & Kealy, RD (2003) Improved glucose tolerance with lifetime diet restriction favorably affects disease and survival in dogs. J Nutr 133, 28872892.
9 Lesser, GT, Deutsch, S & Markofsky, J (1973) Aging in the rat: longitudinal and cross-sectional studies of body composition. Am J Physiol 225, 14721478.
10 Lesser, GT, Deutsch, S & Markofsky, J (1980) Fat-free mass, total body water, and intracellular water in the aged rat. Am J Physiol 238, R82R90.
11 Yu, BP, Masoro, EJ, Murata, I, Bertrand, HA & Lynd, FT (1982) Lifespan study of SPF Fischer 344 male rats fed ad libitum or restricted diets: longevity, growth, lean body mass and disease. J Gerontol 37, 130141.
12 Pamuk, ER, Williamson, DF, Serdula, MK, Madans, J & Byers, TE (1993) Weight loss and subsequent death in a cohort of US adults. Ann Int Med 119, 744778.
13 Wallace, JI & Schwartz, RS (1997) Involuntary weight loss in elderly outpatients. Clin Geriatr Med 13, 717735.
14 Bales, CW & Ritchie, CS (2002) Sarcopenia, weight loss, and nutritional frailty in the elderly. Annu Rev Nutr 22, 399423.
15 Doherty, TJ (2003) Invited review: aging and sarcopenia. J Appl Physiol 95, 17171727.
16 Caso, G & Garlick, PJ (2005) Control of muscle protein kinetics by acid–base balance. Curr Opin Clin Nutr Metab Care 8, 7376.
17 Roff, DA & Mousseau, TA (1987) Quantitative genetics and fitness: lessons from Drosophila. Heredity 58, 103118.
18 Herskind, AM, McGue, M, Holm, NV, Thorkild, I, Sorensen, A, Harvald, B & Vaupel, JW (1996) The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum Genet 97, 319323.
19 Bodkin, NL, Metzger, BL & Hansen, BC (1989) Hepatic glucose production and insulin sensitivity preceding diabetes mellitus in monkeys. Am J Physiol 256, E676E681.
20 Kemnitz, JW, Roecker, EB, Weindruch, R, Elson, DF, Baum, ST & Bergman, RN (1994) Dietary restriction increases insulin sensitivity and lowers blood glucose in rhesus monkeys. Am J Physiol 266, E540E547.
21 Lane, MA, Ball, SS, Ingram, DK, Cutler, RG, Engel, J, Read, V & Roth, GS (1995) Diet restriction in rhesus monkeys lowers fasting and glucose-stimulated glucoregulatory end points. Am J Physiol 268, E941E948.
22 Gresl, TA, Colman, RJ, Roecker, EB, Havighurst, TC, Huang, Z, Allison, DB, Bergman, RN & Kemnitz, JW (2001) Dietary restriction and glucose regulation in aging rhesus monkeys: a follow-up report at 8·5 yr. Am J Physiol Endocrinol Metab 281, E757E765.
23 Bergman, RN (1989) Toward physiological understanding of glucose tolerance. Diabetes 38, 15121527.
24 Bodkin, NL, Alexander, TM, Ortmeyer, HK, Johnson, E & Hansen, BC (2003) Mortality and morbidity in laboratory-maintained rhesus monkeys and effects of long-term dietary restriction. J Gerontol 58A, 212219.
25 Galvin, P, Ward, G, Walters, J, Pestell, R, Koschmann, M, Vaag, A, Martin, I, Best, JD & Alford, F (1992) A simple method for quantitation of insulin sensitivity and insulin release from an intravenous glucose tolerance test. Diabetic Med 9, 921928.
26 Bogardus, C, Lillia, S, Mott, DM, Hollenbeck, C & Reaven, G (1985) Relationship between degree of obesity and in vivo insulin action in man. Am J Physiol 248, E286E291.
27 Bodkin, NL, Hannah, JS, Ortmeyer, HK & Hansen, BC (1993) Central obesity in rhesus monkeys: association with hyperinsulinemia, insulin resistance and hypertriglyceridemia? Int J Obes 17, 5361.
28 Sinclair, DA (2005) Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev 126, 9871002.
29 Kienzle, E, Opitz, B, Earle, KE, Smith, PM, Maskell, IE & Iben, C (1998) An improved method for the estimation of energy in pet foods. J Nutr 128, 2806S2808S.
30 Larson, BT, Lawler, DF & Kealy, RD (2004) Metabolizable energy requirement for maintenance based on body mass components of diet-restricted and control-fed dogs. FASEB 18, A378.
31 Masoro, EF, McCarter, RJM, Katz, MS & McMahan (1992) Dietary restriction alters characteristics of glucose fuel use. J Gerontol 47, B202B208.
32 DeLany, JP, Hansen, BC, Bodkin, NL, Hannah, J & Bray, GA (1999) Long-term calorie restriction reduces energy expenditure in aging monkeys. J Gerontol 54A, B5B11.
33 Wang, Y, Lawler, D, Larson, B, Ramadan, Z, Kochhar, S, Holmes, E & Nicholson, JK (2007) Metabonomic investigations of aging and caloric restriction in a life-long dog study. J Prot Res 6, 18461854.
34 Greeley, EH, Ballam, JM, Harrison, JM, Kealy, RD, Lawler, DF & Segre, M (2001) The influence of age and sex on the immune system: a longitudinal study in Labrador Retriever dogs. Vet Immunol Immunopathol 82, 5771.
35 Greeley, EH, Kealy, RD, Ballam, JM, Lawler, DF & Segre, M (1996) The influence of age on the canine immune system. Vet Immunol Immunopathol 55, 110.
36 Greeley, EH, Spitznagel, E, Lawler, DF, Kealy, RD & Segre, M (2006) Modulation of canine immunosenescence by life-long caloric restriction. Vet Immunol Immunopathol 111, 287299.
37 Effros, RB, Walford, RL, Weindruch, R & Mitcheltree, C (1991) Influences of dietary restriction on immunity to influenza in aged mice. J Gerontol 46, B142B147.
38 Riley-Roberts, M-L, Turner, RJ, Evans, PM & Merry, BJ (1992) Lymphoproliferative responses in diet-restricted and aging Sprague–Dawley rats. Exp Gerontol 27, 201209.
39 Jolly, CA (2004) Dietary restriction and immune function. J Nutr 134, 18531856.
40 Pahlavani, MA (2004) Influence of caloric restriction on aging immune system. J Nutr Health Aging 8, 3847.
41 Nikolich-Zugich, J & Messaoudi, I (2005) Mice and flies and monkeys too: caloric restriction rejuvenates the aging immune system of non-human primates. Exp Gerontol 40, 884893.
42 Merry, BJ (2004) Oxidative stress and mitochondrial function with aging – the effects of calorie restriction. Aging Cell 3, 712.
43 Stowe, HD, Lawler, DF & Kealy, RD (2006) Influences of limit-feeding and aging on antioxidant status of pair-fed Labrador retrievers. J Nutr 136, 18441848.
44 Lawler, DF, Ballam, JM, Meadows, R, Larson, BT, Li, Q & Kealy, RD (2007) Influence of lifetime food restriction on selected hematology and clinical chemistry in dogs. Exp Gerontol 42, 204214.
45 Liepa, GU, Masoro, EJ, Bertrand, HA & Yu, BP (1980) Food restriction as a modulator of age-related changes in serum lipids. Am J Physiol 238, E253E257.
46 Masoro, EJ, Compton, C, Yu, BP & Bertrand, H (1983) Temporal and compositional dietary restrictions modulate age-related changes in serum lipids. J Nutr 113, 880892.
47 van Liew, JB, Davis, PJ, Davis, FB, Bernardis, LL, Deziel, MR, Marinucci, LN & Kumar, D (1993) Effects of aging, diet and sex on plasma glucose, fructosamine, and lipid concentrations in barrier-raised Fischer 344 rats. J Gerontol 48, B184B190.
48 Choi, YS, Goto, S, Ikeda, I & Sugano, M (1988) Age-related changes in lipid metabolism in rats: the consequences of moderate food restriction. Biochim Biophys Acta 963, 237242.
49 Schalk, BWM, Visser, M, Penninx, BWJH, Baadenhuijsen, H, Bouter, LM & Deeg, DJH (2005) Change in serum albumin and subsequent decline in functional status in older persons. Aging Clin Exp Res 17, 297305.
50 Lawler, DF, Johnston, SD, Keltner, DG, Ballam, JM, Kealy, RD, Bunte, T, Lust, G, Mantz, SL & Nie, RC (1999) Influence of restricted feed intake on estrous cycles and pseudopregnancies in female Labrador Retriever dogs. Am J Vet Res 60, 820825.
51 Nelson, JE, Gosden, RG & Felicio, IS (1985) Effect of dietary restriction on estrous cyclicity and follicular reserves in aging C57/BL/6J mice. Biol Reprod 32, 515522.
52 McShane, TM & Wise, PM (1996) Life-long moderate caloric restriction prolongs reproductive life span in rats without interrupting estrous cyclicity: effects on the gonadotropin-releasing hormone/luteinizing hormone axis. Biol Reprod 54, 7075.
53 Lawler, DF, Johnston, SD, Ballam, JM & Kealy, RD (1996) Response to gonadotropin releasing hormone in food restricted and control-fed intact male Labrador retrievers. Paper presented at the International Congress on Animal Reproduction Satellite Meeting, Sydney, Australia.
54 Chen, H, Luo, L, Liu, J, Brown, T & Zirkin, B (2005) Aging and caloric restriction: effects on Leydig cell steroidogenesis. Exp Gerontol 40, 498505.
55 Jervis, KM & Robaire, B (2003) Effects of caloric restriction on gene expression along the epididymis of the Brown Norway rat during aging. Exp Gerontol 38, 549560.
56 Weindruch, R, Walford, RL, Fligiel, S & Guthrie, D (1986) The retardation of aging in mice by dietary restriction – longevity, cancer, immunity, and lifetime energy-intake. J Nutr 116, 641654.
57 Kirkwood, TBL & Shanley, DP (2005) Food restriction, evolution and ageing. Mech Ageing Dev 126, 10111016.
58 Teillet, L, Gouraud, S & Corman, B (2004) Does food restriction increase life span in lean rats? J Nutr Health Aging 8, 213218.
59 Weindruch, R & Walford, RL (1988) The Retardation of Aging and Disease by Dietary Restriction. Springfield, IL: Charles C. Thomas Publishers.
60 Hill, RC, Lewis, DD, Randell, SC, Scott, KC, Omori, M, Sundstrom, DA, Jones, GL, Speakman, JR & Butterwick, RF (2005) Effect of mild restriction of food intake on the speed of racing greyhounds. Am J Vet Res 66, 10651070.
61 Holloszy, JO (1997) Mortality rate and longevity of food-restricted exercising male rats: a re-evaluation. Am J Physiol 82, 399403.
62 Weed, JL, Lane, MA, Roth, GS, Speer, DL & Ingram, DK (1997) Activity measures in rhesus monkeys on long-term calorie restriction. Physiol Behav 62, 97103.
63 Masoro, EJ (1993) Dietary restriction and aging. J Am Geriatr Soc 41, 994999.
64 Saxton, JA & Kimball, GC (1941) Relation of nephrosis and other diseases of albino rats to age and to modifications of diet. Arch Pathol 32, 951965.
65 Berg, BN & Sims, HS (1960) Nutrition and longevity in the rat. II. Longevity and onset of disease with different levels of food intake. J Nutr 71, 255263.
66 Tucker, SM, Mason, RL & Beauchene, RE (1976) Influence of diet and food restriction on kidney function of aging male rats. J Gerontol 31, 264270.
67 Maeda, H, Gleiser, CA, Masoro, EJ, Murata, I, McMahan, CA & Yu, BP (1985) Nutritional influence on aging of Fischer 344 rats. II. Pathology. J Gerontol 40, 671688.
68 Shimokawa, I, Higami, Y & Hubbard, GB (1993) Diet and the suitability of the male Fischer 344 rat as a model for aging research. J Gerontol 48, B27B32.
69 Lloyd, T (1984) Food restriction increases life span of hypertensive animals. Life Sci 34, 401407.
70 Natelson, BH, Ottenweller, JE, Servatius, RJ, Drastal, S, Bergen, MT & Tapp, WN (1992) Effect of stress and food restriction on blood pressure and life span of Dahl salt-sensitive rats. J Hypertens 10, 14571462.
71 Fernandes, G, Friend, P, Yunis, EJ & Good, RA (1978) Influence of dietary restriction on immunologic function and renal disease in (NZB × NZW)F1 mice. Proc Natl Acad Sci U S A 75, 15001504.
72 Taylor, A, Zuliani, AM, Hopkins, RE, Dallal, GE, Treglia, P, Kuck, JFR & Kuck, K (1989) Moderate caloric restriction delays cataract formation in the Emory mouse. FASEB 3, 17411746.
73 Kubo, C, Day, NK & Good, RA (1984) Influence of early or late dietary restriction on life span and immunological parameters in MRL/Mp-lpr/lpr mice. Proc Natl Acad Sci U S A 81, 58315835.
74 Tannenbaum, A (1940) The initiation and growth of tumors. Introduction. I. Effects of underfeeding. Am J Cancer 38, 335350.
75 Saxton, JA Jr, Boon, MC & Furth, J (1944) Observations on the inhibition of development of spontaneous leukemia in mice by underfeeding. Cancer Res 4, 401409.
76 Shimokawa, I, Yu, BP & Masoro, EJ (1991) Influence of diet on fatal neoplastic disease in male Fischer 344 rats. J Gerontol 46, B228B232.
77 Rehm, S, Rapp, KG & Deerberg, F (1985) Influence of food restriction and body fat on life span and tumor incidence in female outbred Han: NMRI mice and two sublines. Z Versuchstierkd 27, 249283.
78 Ross, MH & Bras, G (1971) Lasting influence of early caloric restriction on prevalence of neoplasms in the rat. J Nat Cancer Inst 47, 10951113.
79 Molon-Noblot, S, Keenan, KP, Coleman, JB, Hoe, C-M & Laroque, P (2001) The effects of ad libitum overfeeding and moderate and marked dietary restriction on age-related spontaneous pancreatic islet pathology in Sprague–Dawley rats. Toxicol Pathol 29, 353362.
80 Thurman, JD, Bucci, TJ, Hart, RW & Turturro, A (1994) Survival, body weight, and spontaneous neoplasms in ad libitum-fed and food-restricted Fischer-344 rats. Toxicol Pathol 22, 19.
81 Safai-Kutti, S, Fernandes, G, Wang, Y, Safai, B, Good, RA & Day, ND (1980) Reduction of circulating immune complexes by calorie restriction in (NZB × NZW) F1 mice. Clin Immunol Immunopathol 15, 293300.
82 Duffy, PH, Lewis, SM, Mayhugh, MA, Trotter, RW, Thorn, BT, Feuers, RJ & Turturro, A (2004) The effects of different levels of dietary restriction on non-neoplastic diseases in male Sprague–Dawley rats. Aging Clin Exp Res 16, 6878.
83 Lane, MA, Black, A, Ingram, DK & Roth, GS (1998) Calorie restriction in non-human primates. Implications for age-related disease. J Antiaging Med 1, 315326.
84 Hansen, BC, Bodkin, NL & Ortmeyer, HK (1999) Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality. Toxicol Sci 52, Suppl., 5660.
85 Smith, GK, Lawler, DF, Powers, MY, Biery, DN, Shofer, FS, McKelvie, PJ, Paster, E & Kealy, RD (2006) Diet restriction and radiographic evidence of osteoarthritis in dogs. J Am Vet Med Assoc 229, 690693.
86 Kealy, RD, Lawler, DF, Ballam, JM, Lust, G, Biery, DN, Smith, GK & Mantz, SM (2000) Evaluation of the effect of limited food consumption on radiographic evidence of osteoarthritis in dogs. J Am Vet Med Assoc 217, 16781680.
87 Lawler, DF, Larson, BT, Lust, G, Smith, GK, Biery, DN, Evans, RH, Spitznagel, EL & Kealy, RD (2003) Influence of lifetime diet restriction on bone minerals in Labrador retriever dogs. In Proceedings of the Nestle Purina Nutrition Forum, St. Louis, MO.
88 Black, A, Allison, DB, Shapses, SA, Tilmont, EM, Handy, AM, Ingram, DK, Roth, GS & Lane, MA (2001) Calorie restriction and skeletal mass in rhesus monkeys (Macaca mulatta): evidence for an effect mediated through changes in body size. J Gerontol 56A, B98B107.
89 LaMothe, JM, Hepple, RT & Zernicke, RF (2003) Selected contribution: bone adaptation with aging and long-term caloric restriction in Fischer 344 × Brown-Norway F1-hybrid rats. J Appl Physiol 95, 17391745.
90 Ross, MH (1976) Nutrition and longevity in experimental animals. In Nutrition and Aging, pp. 4357 [Winick, M, editor]. New York: Wiley.
91 Thompson, HJ, Zhu, Z & Jiang, W (2002) Protection against cancer by energy restriction: all experimental approaches are not equal. J Nutr 132, 10471049.
92 Li, SY, Li, J, Singh, NP, Cowan, GM Jr, Buffinton, C & Hart, RW (1998) DNA damage and repair in morbidly obese patients after gastric bypass surgery. In Abstracts of the SOT Conference: ‘The Role of Diet and Caloric Intake in Aging, Obesity, and Cancer’, p. 47.
93 Hart, RW, Dixit, R, Seng, J, et al. (1999) Adaptive role of caloric intake on the degenerative disease processes. Toxicol Sci 52, Suppl., 312.
94 Hursting, SD, Lavigne, JA, Berrigan, D, Perkins, SN & Barrett, JC (2003) Calorie restriction, aging, and cancer prevention: mechanisms of action and applicability to humans. Annu Rev Med 54, 131152.
95 Partridge, L, Pletcher, SD & Mair, W (2005) Dietary restriction, mortality trajectories, risk and damage. Mech Ageing Dev 126, 3541.



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