Our studies are directed toward understanding the nature of the mesenchymal cell that develops
along the osteoblast lineage. These studies include the changes in gene expression under differing
culture conditions, the effect of oxidative challenge, and the development of osteopenia in a mouse
model lacking telomerase, as well as alterations in mitochondrial function with animal age and under
oxidative stress.
Studies of aging at the cellular level/age-related cataract are directed toward determining the
causes and mechanisms of aging at the cellular level. We are studying age-related alterations in
the in vitro proliferative capacity and in vivo replicative activity of cells of the following
lineages: lens epithelial cells, hepatocytes, pancreatic acinar cells, kidney tubular cells, dermal
fibroblasts, and marrow stromal osteoblasts. The conservation of proliferative capacity by longterm
caloric restriction has been determined for all of the above tissues. A number of new techniques
are being applied in these studies, which include measurements of DNA damage as determined by the
gel migration (comet) assay and also age-related changes in mitochondrial mass, mitochondrial
membrane potential, mitochondrial H202 production and mitochondrial oxidative metabolism. These
measurements are carried out with specific fluorescent dyes, using either laser-activated confocal
microscopy or by FLOW. In addition, a specific telomere sequence probe allows measurement of
telomere length on small cell samples by in situ hybridization. Alterations in cell cycle-related
gene expression in these cells, as correlatedwith age and reduction in replicative capacity, is a
projected future project.
Current collaborations include 1. a study comparing the time of development of cataracts in
genetically randomized mice, with the intent of determining the quantum trait loci connected to
cataract formation and of this relationship to life span; 2. a determination of cataract development
time and lens cell function in mice that are either transgenic for overexpression of specific
anti-oxidant genes or with such genes knocked out; 3. a study of cataract occurence and osteopenia
in telomerase knockout mice with age and successive generations of knockout; and 4. a projected
study of mitochondrial efficiency in long-lived mice with reduced GH, IGF-1, and body size.
Dr. Wolf has been Professor, Department of Pathology, and Adjunct Professor, Department of
Comparative Medicine, since 1990. He is currently scientific board member, Journal of American
Aging Association.
Selected Relevant Publications
Wang QR, Yan Y, Wang BH, Li WM, Wolf NS. Long-term culture of murine bone-marrow-derived
endothelial cells. In Vitro Cell Dev Biol-Animal 34:443-446, 1998.
Pendergrass WR, Lane MA, Bodkin NL, Hansen BC, Ingram DK, Roth GS, Yi L, Bin H, Wolf NS. Cellular
proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta).
J Cell Physiol 180:123-130, 1999.
Wolf NS, Pendergrass WR. The relationships of animal age and caloric intake to cellular replication
in vivo and in vitro: a review. J Gerontol 54A:B502-17, 1999.
Wolf NS, Yi L, Schmeider C, Pendergrass WR, Turturro A. Normal mouse and rat strains as models
for human cataract formation, protection by CR. Exp Eye Res 70: 683-692, 2000.
Wolf NS, Penn PE. The effect of high and very low fluorescent light exposure levels on age-related
cataract in a pigmented mouse strain. Exp Eye Res 73:37-43, 2001.
Pendergrass WR, Penn PE, Li J, Wolf NS. Age-related telomere shortening occurs in lens epithelium
from old rats and is slowed by caloric restriction. Exp Eye Res 73:221-8, 2001.
