In this study we will complete our comprehensive characterization of the age-related pathology of all groups of animals in the Biomarker Program, including all 7 genotypes, 2 species, 2 genders and 2 diet groups sacrificed at 6 month intervals. The data will be of great value to other experimental gerontologists. We will also test the hypothetical mechanism that caloric restriction (CR) prolongs life primarily by suppressing cell replication. By doing so it inhibits the development of tumors, the main cause of death of rodents, as well as inflammatory and autoimmune diseases. We will test the hypothesis by collecting and analyzing pathology data to determine the extent to which CR has a greater effect on suppressing proliferative lesions, those involving increases in numbers of cells, than on suppressing degenerative lesions, those involving cell death. We will quantitate the severity of 3 purely degenerative lesions of mice-neuronal lipofuscinosis, neuroaxonal dystrophy and osteopenia, and of 4 lesions that involve cellular replication in response to degenerative processes, arthropathy, white matter gliosis and fibrous osteodystrophy. Further tests of the hypothesis will involve studies of the effects of CR on non-pathologic spontaneous and induced cell replication in hair follicles. We will study the effects of aging and CR on regrowth of hair after shaving and after plucking, which induces follicles into the replicative anagen phase of growth. We will monitor cell replication by labelling hair bulb cells with bromodeoxyuridine. These studies of hair may provide new relatively non-invasive biomarkers of aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Biological and Clinical Aging Review Committee (BCA)
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Tufts University
Schools of Medicine
United States
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Obin, M; Pike, A; Halbleib, M et al. (2000) Calorie restriction modulates age-dependent changes in the retinas of Brown Norway rats. Mech Ageing Dev 114:133-47
Obin, M; Halbleib, M; Lipman, R et al. (2000) Calorie restriction increases light-dependent photoreceptor cell loss in the neural retina of fischer 344 rats. Neurobiol Aging 21:639-45
Lipman, R D; Dallal, G E; Bronson, R T (1999) Lesion biomarkers of aging in B6C3F1 hybrid mice. J Gerontol A Biol Sci Med Sci 54:B466-77
Lipman, R D; Dallal, G E; Bronson, R T (1999) Effects of genotype and diet on age-related lesions in ad libitum fed and calorie-restricted F344, BN, and BNF3F1 rats. J Gerontol A Biol Sci Med Sci 54:B478-91
Lipman, R D; Smith, D E; Blumberg, J B et al. (1998) Effects of caloric restriction or augmentation in adult rats: longevity and lesion biomarkers of aging. Aging (Milano) 10:463-70
Lipman, R D; Bronson, R T; Wu, D et al. (1998) Disease incidence and longevity are unaltered by dietary antioxidant supplementation initiated during middle age in C57BL/6 mice. Mech Ageing Dev 103:269-84
Lipman, R D (1997) Pathobiology of aging rodents: inbred and hybrid models. Exp Gerontol 32:215-28
Lipman, R D; Smith, D E; Bronson, R T et al. (1995) Is late-life caloric restriction beneficial? Aging (Milano) 7:136-9
Bronson, R T; Lipman, R D; Harrison, D E (1993) Age-related gliosis in the white matter of mice. Brain Res 609:124-8
Bronson, R T; Lipman, R D (1993) FRAR course on laboratory approaches to aging. The role of pathology in rodent experimental gerontology. Aging (Milano) 5:253-7

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