Life Span, Morphology, and Pathology of Diet-Restricted Germ-Free and Conventional Lobund-Wistar Rats

Snyder, David; Pollard, Morris; Wostmann, Bernard S.; Luckert, Phyllis H.

doi:10.1093/geronj/45.2.b52

Cited by 72 publications

(50 citation statements)

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“…Body weights of both food-restricted groups of mice were lower than those of their full-fed counterparts. The lower body weight and longer life span observed in relation to food restriction from weaning agree with the results of previous investigator [8,[16][17][18]23]. The importance of low body weight in longevity is indicated by the long mean life span of the foodrestricted mice.…”

Section: Disussionsupporting

confidence: 90%

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Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

Tazume

Umehara

Matsuzawa

et al. 1991

Experimental Animals

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An investigation was undertaken to study the effects of germfree (GF) status and mild food restriction on life span in GF and specific pathogen-free (SPF) male ICR mice either full-fed (ad libitum) or on a restricted diet of 4.5 grams per day (equivalent to approximately 80% of full-fed intake) from five-week-old. The mean life span of the full-fed SPF and GF mice was 75.9 and 88.9 weeks respectively, whie the mean life span of the food-restricted SPF and GF mice was 117.5 and 109.6 weeks, respectively. Mice in both GF and SPF food-restricted groups were characterized by lower body weight and increased survival. These findings suggest that the cessation of growth may be importantly and perhaps causally related to longevity. The GF mice survived longer than the SPF mice, but the combination of GF status with food restriction did not seem to extend life span more than food restriction alone.

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Section: Disussionsupporting

confidence: 90%

“…However, Little is known about aging processes in GF animals subjected to food restriction from weaning through their usual or extended life spans [12,17,18] . Hence, the present investigation was designed to examine both the effects of GF status and food restriction on the longevity and growth of mice.…”

mentioning

confidence: 99%

Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

Tazume

Umehara

Matsuzawa

et al. 1991

Experimental Animals

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“…In both GF and SPF mice, food-restricted mice (to 80% of fullfed controls) survived longer than full-fed mice. This results was in agreement with Snyder et al [19,20] reporting longer survival for food-restricted GF and CV rats than their full-fed counterparts.…”

Section: Discussionsupporting

confidence: 93%

Immunological Function of Food-restricted Germfree and Specific Pathogen-free Mice

Tazume

Umehara

Matsuzawa

et al. 1991

Experimental Animals

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The effects of food restriction on immune function was investigated in germfree (GF) and specific pathogen-free (SPF) mice. They were maintained from five weeks of age under either full-fed or food-restricted conditions to 4.5 grams per day (equivalent to approximately 80% of full-fed intake) of a commercial diet. Longest survival rate was attained in food-restricted SPF mice followed by food-restricted GF, full-fed GF, and full-fed SPF animals. Food-restricted GF mice showed shorter survival rate than their SPF counterparts. This result suggests that food restriction may be just as effective as GF status for extending life span. Immune function declined significantly with age in full-fed groups of GF and SPF mice. In both foodrestricted GF and SPF mice, mitogenic response to concanavalin A or lipopolysaccharide and antibody response to sheep red blood cells were lower early in life and became higher later in life as compared with full-fed mice. Hence, the maintenance of effective immunological function until old age may be the reason for food-restricted groups to live slightly longer than full-fed groups.

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“…We used 12-and 26-monthold Lobund-Wistar rats to investigate the molecular basis for the up-regulation of L-type channel activity in aging rats. The mean lifespan of this rat strain is Ϸ30 months (38). Age-related primary changes should appear earlier than secondary effects.…”

Section: Resultsmentioning

confidence: 93%

Increased phosphorylation of the neuronal L-type Ca ²⁺ channel Ca _v 1.2 during aging

Davare

Hell

2003

Proc. Natl. Acad. Sci. U.S.A.

110

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An increase in Ca 2؉ influx through L-type Ca 2؉ channels is thought to contribute to neuronal dysfunctions that underlie senile symptoms and Alzheimer's disease. The molecular basis of the agedependent up-regulation in neuronal L-type Ca 2؉ channel activity is largely unknown. We show that phosphorylation of the L-type channel Ca v1.2 by cAMP-dependent protein kinase is increased >2-fold in the hippocampus of aged rats. The hippocampus is critical for learning and is one of the first brain regions to be affected in Alzheimer's disease. Phosphorylation of Ca v1.2 by cAMP-dependent protein kinase strongly enhances its activity. Therefore, increased Ca v1.2 phosphorylation may account for a substantial portion of the age-related rise in neuronal Ca 2؉ influx and its neuropathological consequences. C a 2ϩ regulates a variety of signaling pathways (1-3). Acute uncontrolled Ca 2ϩ influx can cause neuronal death by overstimulation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor (4, 5). Chronic elevation of Ca 2ϩ influx has been implicated in age-associated neuronal loss and Alzheimer's disease (6, 7). The age-related learning impairment in rabbits is reversed by the specific L-type Ca 2ϩ channel blocker nimodipine (8). These observations indicate that elevation of L-type channel activity causes neuronal dysfunction during aging. Ca 2ϩ influx through L-type channels is up-regulated Ͼ2-fold in hippocampal neurons of old versus adult rats (9). The hippocampus is crucial for learning and memory; however, the molecular basis for the increase in L-type channel activity during aging is not well defined, except for an Ϸ20% increase in Ca v 1.3 protein (10, 11). We now show that cAMP-dependent protein kinase (PKA)-mediated phosphorylation of the L-type channel Ca v 1.2 increases Ͼ2-fold during aging and that it may underlie a substantial portion of the age-related increase in L-type channel activity.PKA increases L-type channel activity in neurons (13-16) and in the heart, where PKA-dependent stimulation of the cardiac L-type channel is crucial for the up-regulation of the heartbeat after adrenergic stimulation (17, 18 (19), and the auxiliary subunits ␣ 2 -␦, -␤, and -␥ (22). Only ␣ 1 1.2, and none of the auxiliary subunits, is required for the PKA-mediated increase in channel activity (23). ␣ 1 1.2 is phosphorylated in intact hippocampal neurons by PKA (24). The main phosphorylation site on ␣ 1 1.2 is serine 1928 (25, 26), which is important for the up-regulation of the channel activity by PKA (27). This site is close to the C terminus of ␣ 1 1.2, is present only in the full-length form of ␣ 1 1.2 (21), and is removed by the Ca 2ϩ -activated protease calpain after Ca 2ϩ influx through NMDA receptors (28). Calpain cleaves ␣ 1 1.2 Ϸ300 residues upstream of the C terminus in vitro (28). Deletion of the last 300-400 residues of ␣ 1 1.2 increases channel activity when expressed in Xenopus oocytes (29); therefore, calpain-mediated cleavage may permanently elevate Ca v 1.2 activity in vivo. Because calpain has been impli...

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Life Span, Morphology, and Pathology of Diet-Restricted Germ-Free and Conventional Lobund-Wistar Rats

Cited by 72 publications

References 0 publications

Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

Immunological Function of Food-restricted Germfree and Specific Pathogen-free Mice

Increased phosphorylation of the neuronal L-type Ca ²⁺ channel Ca _v 1.2 during aging

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Life Span, Morphology, and Pathology of Diet-Restricted Germ-Free and Conventional Lobund-Wistar Rats

Cited by 72 publications

References 0 publications

Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

Immunological Function of Food-restricted Germfree and Specific Pathogen-free Mice

Increased phosphorylation of the neuronal L-type Ca 2+ channel Ca v 1.2 during aging

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Increased phosphorylation of the neuronal L-type Ca ²⁺ channel Ca _v 1.2 during aging