Dietary caloric restriction provides the only known method to extend mean and maximal lifespan and to delay the onset of a variety of late-life diseases. The applicant recently used 21 percent moderate dietary caloric restriction regimes in the first successful attempt to delay senile-type cataract as modeled in the Emory mouse (22). Preliminary studies with 40 percent dietary caloric restriction show even more impressive retardation of cataract. Elucidation of the mechanisms by which caloric restriction results in delayed cataract would allow unique opportunities to delay human cataract without the extreme, and questionably pleasurable, changes in eating patterns. Such information should also help set directions for future cataract research. The Emory mouse is a useful model in which to study the mechanisms by which dietary restriction prolongs lens clarity because it develops cataracts which, like human cataracts, are of post-maturity onset and which originate primarily but not exclusively in the lens nucleus. These cataracts also show many biochemical and morphological similarities to human cataracts. (**Depleted: comparisons between C3B mice and Emory mice.) The applicant and his coworker's initial studies of lens proteins suggest that caloric restriction is associated with extended maintenance of protein integrity, perhaps involving prolonged antioxidant and/or proteolytic capabilities. It is also associated with diminished plasma glucose, glycohemoglobin and diminished lens protein-glycation (nonenzymatic glycosylation). Excessive bodily DNA damage is not suggested in our preliminary studies. Thus, they would study relationships between the delay of cataract and a) antioxidant and/or; b) proteolytic capabilities; c) protein glycation; and d) DNA damage as they are affected by aging and caloric restriction. Parts of studies c and d would be done with collaborators. Since diabetics are known: 1) to have higher circulating glucose; 2) to have four times the incidence of cataract at young ages; and 3) to have many of the same types of protein damage in their lenses as is seen in senile cataracts, it is probable that their conclusions would lead to ways to delay both senile and diabetic cataract.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY008566-01A1
Application #
3265937
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1991-02-01
Project End
1995-01-31
Budget Start
1991-02-01
Budget End
1992-01-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
Scrofano, M M; Shang, F; Nowell Jr, T R et al. (1998) Aging, calorie restriction and ubiquitin-dependent proteolysis in the livers of Emory mice. Mech Ageing Dev 101:277-96
Scrofano, M M; Jahngen-Hodge, J; Nowell Jr, T R et al. (1998) The effects of aging and calorie restriction on plasma nutrient levels in male and female Emory mice. Mech Ageing Dev 105:31-44
Scrofano, M M; Shang, F; Nowell Jr, T R et al. (1998) Calorie restriction, stress and the ubiquitin-dependent pathway in mouse livers. Mech Ageing Dev 105:273-90
Taylor, A; Nowell, T (1997) Oxidative stress and antioxidant function in relation to risk for cataract. Adv Pharmacol 38:515-36
Taylor, A; Jacques, P F; Nowell, T et al. (1997) Vitamin C in human and guinea pig aqueous, lens and plasma in relation to intake. Curr Eye Res 16:857-64
Gong, X; Shang, F; Obin, M et al. (1997) Antioxidant enzyme activities in lens, liver and kidney of calorie restricted Emory mice. Mech Ageing Dev 99:181-92
Shang, F; Gong, X; Palmer, H J et al. (1997) Age-related decline in ubiquitin conjugation in response to oxidative stress in the lens. Exp Eye Res 64:21-30
Shang, F; Taylor, A (1995) Oxidative stress and recovery from oxidative stress are associated with altered ubiquitin conjugating and proteolytic activities in bovine lens epithelial cells. Biochem J 307 ( Pt 1):297-303
Taylor, A; Jacques, P F; Epstein, E M (1995) Relations among aging, antioxidant status, and cataract. Am J Clin Nutr 62:1439S-1447S
Shang, F; Huang, L; Taylor, A (1994) Degradation of native and oxidized beta- and gamma-crystallin using bovine lens epithelial cell and rabbit reticulocyte extracts. Curr Eye Res 13:423-31

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