From: Doug Skrecky (oberon@vcn.bc.ca)
Date: Sat Aug 29 1998 - 05:45:36 MDT
Authors
Bernardis LL. Davis PJ.
Institution
Neurovisceral-Neuroendocrine Laboratory, Veterans Affairs Medical Center,
Buffalo, NY 14215, USA.
Title
Aging and the hypothalamus: research perspectives. [Review]
[220 refs]
Source
Physiology & Behavior. 59(3):523-36, 1996 Mar.
Abstract
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. [References: 220]
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