Enhanced cell proliferation and biosynthesis mediate improved wound repair in refed, caloric-restricted mice

Reed, May J.; Penn, Philip; Li, Y.; Birnbaum, Roger S.; Vernon, Robert B.; Johnson, Timothy S.; Pendergrass, William R.; Sage, E. Helene; Abrass, Itamar B.; Wolf, Norman S.

doi:10.1016/0047-6374(96)01737-x

Cited by 91 publications

(76 citation statements)

References 46 publications

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“…Similar to data from a previous study in aged mice (Reed et al 1996), we observed that refeeding young calorie-restricted rats for a 48-h period prior to wounding resulted in wound healing resembling that observed in AL rats and that was superior to that observed in CR rats, the group that had the poorest wound healing. We cannot determine possible mechanisms that may be involved in this rapid recovery in the young refed CR rat since we did not evaluate the wounds histologically or perform any in vitro experiments.…”

Section: Discussionsupporting

confidence: 88%

“…Rats were assigned to one of three diet groups that received three skin punch wounds along the dorsal interscapular region (12-mm diameter near the front limbs) of the back as follows: (1) CR (n=8) were wounded and maintained on CR until they healed, (2) AL (n=5) were wounded and maintained on AL until wound closure was completed, and (3) CR rats were refed (RF, n=9) AL for 48 h prior to wounding and maintained on AL until they healed. We observed that young rats on CR healed more slowly while CR rats refed for 48 h prior to wounding healed as fast as AL fed rats, similar to a study reported in aged CR and RF mice (Reed et al 1996). Our data suggest that CR subjects, regardless of age, fail to heal well and that provision of increased nutrition to CR subjects prior to wounding enhances the healing process.…”

supporting

confidence: 88%

“…The groupings were (1) CR rats consuming 40% less than AL fed rats prior to and throughout the wound healing study, (2) AL fed rats that were fed AL prior to and throughout the wound healing study, and (3) CR rats that consumed 40% less than AL until 48 h prior to wounding when they were refed AL and maintained on AL feeding throughout the study. Our hypothesis was that refeeding prior to wound healing in young rats on CR until 48 h prior to wounding would enhance recovery and closure of wounds in the RF group, similar to the results observed in the middle-aged and aged mice in the Reed et al (1996) study.…”

Section: Introductionsupporting

confidence: 72%

“…However, its effects on wound healing have not appeared to be as beneficial (Reiser et al 1995;Roth et al 1997). Reed et al (1996) performed an extensive study comparing the wound healing of AL fed young and middle-aged mice to aged mice that had been fed AL, CR ,and CR that were refed AL for 1 month prior to wounding. Aged refed mice in that study healed at rates similar to the young AL fed mice.…”

Section: Introductionmentioning

confidence: 99%

“…Similar to the study performed by Reed et al (1996) in aged mice, we evaluated wound healing in three different diet groups. The groupings were (1) CR rats consuming 40% less than AL fed rats prior to and throughout the wound healing study, (2) AL fed rats that were fed AL prior to and throughout the wound healing study, and (3) CR rats that consumed 40% less than AL until 48 h prior to wounding when they were refed AL and maintained on AL feeding throughout the study.…”

Section: Introductionmentioning

confidence: 99%

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Effect of calorie restriction and refeeding on skin wound healing in the rat

Hunt

Zhu

et al. 2011

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Calorie restriction (CR) is a reliable antiaging intervention that attenuates the onset of a number of age-related diseases, reduces oxidative damage, and maintains function during aging. In the current study, we assessed the effects of CR and other feeding regimens on wound healing in 7-month-old Fischer-344 rats from a larger cohort of rats that had been fed either ad libitum (AL) or 40% calorie restricted based on AL consumption. Rats were assigned to one of three diet groups that received three skin punch wounds along the dorsal interscapular region (12-mm diameter near the front limbs) of the back as follows: (1) CR (n=8) were wounded and maintained on CR until they healed, (2) AL (n=5) were wounded and maintained on AL until wound closure was completed, and (3) CR rats were refed (RF, n=9) AL for 48 h prior to wounding and maintained on AL until they healed. We observed that young rats on CR healed more slowly while CR rats refed for 48 h prior to wounding healed as fast as AL fed rats, similar to a study reported in aged CR and RF mice (Reed et al. 1996). Our data suggest that CR subjects, regardless of age, fail to heal well and that provision of increased nutrition to CR subjects prior to wounding enhances the healing process.

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Section: Discussionsupporting

confidence: 88%

supporting

confidence: 88%

Section: Introductionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Effect of calorie restriction and refeeding on skin wound healing in the rat

Hunt

Zhu

et al. 2011

AGE

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A deficit in collagenase activity contributes to impaired migration of aged microvascular endothelial cells

et al. 2000

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Angiogenesis is impaired in aging. Delayed neovascularization is due, in part, to slowed endothelial cell migration. Migration requires an optimal level of adhesion to matrix proteins, a process mediated by matrix-degrading metalloproteases (MMPs) such as MMP1. To determine whether impaired angiogenesis in aging is associated with altered synthesis and activity of MMP1, we examined the expression of collagenase and tissue inhibitor of metalloprotease 1 (TIMP1) by immunostain of angiogenic sponge implants from young and aged mice. To characterize the relevance of MMP activity during the movement of aged endothelial cells, the secretion of MMP1 and TIMP1 by late-passage human microvascular endothelial cells (hmEC aged in vitro) and their non-aged (young) counterparts was quantified. The migration of aged human microvascular endothelial cells and the effect of inhibition of TIMP1 on the migration of aged hmEC or collagen I was also measured. Relative to young mice, granulation tissue from aged mice showed less expression of collagenase and increased expression of TIMP1. In vitro, aged hmEC were deficient in MMP1 secretion (55 +/- 13% relative to young cells) and activity but showed increased expression of TIMP1 (280 +/- 109% relative to young cells). Aged hmEC migrated significantly less distance than did young hmEC over a 5-day period (59 +/- 8% relative to young cells). In the presence of a blocking antibody to TIMP1, aged hmEC showed a significant increase in the distance migrated on collagen I over a 5 day period (142 +/- 11% relative to untreated aged hmEC). We propose that deficient MMP1 activity contributes to impaired cellular movement in aged microvascular endothelial cells and that perturbations that enhance collagenase activity increase their migratory ability and angiogenic potential.

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Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta)

et al. 1999

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Caloric restriction (CR) is the most successful method of extending both median and maximal lifespans in rodents and other short-lived species. It is not yet clear whether this method of life extension will be successful in longer-lived species, possibly including humans; however, trials in rhesus monkeys are underway. We have examined the cellular proliferative potential of cells from CR and AL (ad libitum fed) monkey skin cells using two different bioassays: colony size analysis (CSA) of dermal fibroblasts isolated and cloned directly from the skin and beta-galactosidase staining at pH 6.0 (BG-6.0) of epidermal cells in frozen sections of skin. Decreases in both proliferative markers occurred with age, but no differences were observed between CR and AL animals. Skin biopsies were obtained from AL and CR rhesus monkeys from two different aging colonies, one at the National Institute on Aging (NIA) and one at the University of Maryland-Baltimore (UMB). These biopsies were used as a source of tissue sections and cells for two biomarkers of aging assays. The CR monkeys had been maintained for 9-12 years on approximately 70% of the caloric intake of control AL animals. In the CSA studies, the fraction of small clones increased significantly and the fraction of large clones decreased significantly with increasing age in AL monkeys. The frequency of epidermal BG-6.0 staining cells increased with age in older (>22 years) AL monkeys, but most predominately in those of the UMB colony, which were somewhat heavier than the NIH AL controls. Old monkeys on CR tended to have fewer BG-6.0-positive cells relative to old AL-derived epidermis, but this effect was not significant. These results indicate that cellular proliferative potential declined with age in Macaca mulatta, but was not significantly altered by CR under these conditions. Although these experiments are consistent with an absence of effect of CR on monkey skin cell proliferative potential, we have found in previous experiments with mice that a longer duration of CR (as a fraction of total lifespan) was needed to demonstrate CR-related improvement in clone size in mice. Further studies on the now mid-aged monkeys will be needed as their age exceeds 20 years to conclusively rule out an effect of CR on proliferative potential of skin cells from these primates.

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Enhanced cell proliferation and biosynthesis mediate improved wound repair in refed, caloric-restricted mice

Cited by 91 publications

References 46 publications

Effect of calorie restriction and refeeding on skin wound healing in the rat

Effect of calorie restriction and refeeding on skin wound healing in the rat

A deficit in collagenase activity contributes to impaired migration of aged microvascular endothelial cells

Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta)

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