Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are several hypothalamic theories of aging, none of which has been validated. An approach to validation is to search for consequences of anatomic ablations of hypothalamic regions that are functional hallmarks of aging, or consequences of ablation that postpone the appearance of hallmarks of aging or extend longevity. Ablation of the hypothalamic ventromedial nucleus (VMN) in the weanling rat is associated with subsequent increased body fat, glucose intolerance, hyperlipidemia, and decreased renal function. Each of these consequences is characteristic of aging in humans and in several animal models of aging. Ablation of the hypothalamic dorsomedial nucleus (DMN) in the weanling rat leads to a symmetrically smaller animal with normal glucose and lipid metabolism, decreased body fat for size, and reduced risk of decreased renal function and circulating IGF-I levels. These are findings consistent with calorie restriction models in rodents that significantly extend life span. This review compares outcomes of lesions in the VMN, DMN, and lateral hypothalamic area (LHA) for relevance to aging. To establish a relationship between these anatomic areas of the hypothalamus and aging, it is concluded that the VMN, DMN, and LHA lesions should be examined for impact on longevity and compared with data obtained from simultaneously studied intact ad-lib-fed and 40% calorie-restricted animals. Lesioned animals also should be rigorously studied for neurotransmitters (e.g., neuropeptide Y, beta-endorphin, serotonin, corticotropin-releasing factor, and galanin), and for behavioral changes consistent with aging, for accumulation of specific tissue lipofuscin and amyloid that are associated with normal aging and for other age-dependent findings, such as incidence of tumors and cataract.
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PMID:Aging and the hypothalamus: research perspectives. 870 Sep 56

Explanted newborn rat lens epithelial cells were cultured with various concentrations of FGF-2 and/or insulin or IGF-I for 8-20 days. The accumulation of alphaA-, alphaB-, betaA3/1-, betaB2- and gammaA-F-crystallin was measured. During culture with insulin only, i.e. in the absence of fibre cell differentiation, alphaA- and alphaB-crystallin accumulated to the same level as found in differentiating cells. Culture of epithelial cells with IGF-I led to an increase in alphaB-crystallin, but not in alphaA-crystallin. The addition of insulin under differentiation conditions (in the presence of 25 ng ml(-1)FGF-2) augmented the accumulation of alphaA-crystallin 1.5-fold, the accumulation of betaB2-crystallin two-fold and the accumulation of gammaA-F-crystallin five-fold over that found with FGF-2 only. The accumulation of alphaB- and betaA3/1-crystallin was not affected by insulin in the presence of FGF-2. Adding IGF-I to fibre cells differentiating in the presence of 25 ng ml(-1)FGF-2 resulted in a 1.5-fold increase (of questionable statistical significance) in both alphaA- and alphaB-crystallin and a two to three-fold increase in gammaA-F-crystallin compared to cells cultured with FGF-2 only, no significant effect of IGF-I on the accumulation of betaA3/1- or betaB2-crystallin was found. Comparison of the levels of mRNA and protein suggests that insulin acts to increase the level of transcription. Our results show that the response of fibre cells to insulin or IGF-I differs. Hence, even though half the maximum dosage required for the insulin effect was rather high (between 0.1 and >5 micro g), the effect of insulin cannot be merely transmitted by the IGF-I receptor. Our data further predict that insulin or IGF-I increases the overall ratio of beta- and gamma-crystallin to alpha-crystallin in the fibre cell, which could predispose the lens to cataract.
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PMID:Insulin and IGF-I affect the protein composition of the lens fibre cell with possible consequences for cataract. 1084 83