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Low resting metabolic rate is associated with greater lifespan because of a confounding effect of body fatness.

Duarte LC, Speakman JR - Age (Dordr) (2014)

Bottom Line: Fat-free mass (FFM) and fat mass (FM) were both significantly positively related to RMR.After removing the effect of FFM on RMR, the association between RMR and lifespan remained significantly negative; however, after statistically removing the effect of FM on RMR, the significant association between RMR and lifespan disappeared.We conclude that the negative association between RMR and lifespan is primarily due to the effect of FM, with FM positively related to both RMR and mortality and hence RMR negatively to lifespan.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK, l.duarte@abdn.ac.uk.

ABSTRACT
A negative association between resting metabolic rate (RMR) and lifespan is the cornerstone of the rate of living and free-radical damage theories of aging. Empirical studies supporting a negative association of RMR to lifespan may arise from the correlation between RMR and both daily energy expenditure (DEE) and thermoregulatory activity energy expenditure (TAEE). We screened 540 female mice for higher and lower DEE and measured RMR in the resulting 324 (60 %). We then selected 92 mice in which there was no link between residual from the regression of RMR against body mass (BM) and residual of DEE against BM to separate the effects of these traits. Lifespan was not significantly related to body mass, DEE and TAEE, but significantly negatively related to RMR. Fat-free mass (FFM) and fat mass (FM) were both significantly positively related to RMR. After removing the effect of FFM on RMR, the association between RMR and lifespan remained significantly negative; however, after statistically removing the effect of FM on RMR, the significant association between RMR and lifespan disappeared. We conclude that the negative association between RMR and lifespan is primarily due to the effect of FM, with FM positively related to both RMR and mortality and hence RMR negatively to lifespan. In 40 additional screened mice, greater FM was also associated with greater oxidative damage to DNA.

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Survival curves. Cumulative survival curve (Kaplan–Meier survival plot) of female MF1 mice. The cumulative survival rate was plotted against age in days. Log-rank test was performed to compare high and low body mass (a), daily energy expenditure (b), thermoregulatory activity energy expenditure (c) and resting metabolic rate (d) (see text for statistics)
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Fig3: Survival curves. Cumulative survival curve (Kaplan–Meier survival plot) of female MF1 mice. The cumulative survival rate was plotted against age in days. Log-rank test was performed to compare high and low body mass (a), daily energy expenditure (b), thermoregulatory activity energy expenditure (c) and resting metabolic rate (d) (see text for statistics)

Mentions: In the selected sample of 92 individuals that were retained for lifespan analysis, there was no significant relationship between lifespan and body mass (least squares linear regression analysis (LSR): F1,90 = 0.02, P = 0.90; b = −0.4; Fig. 2a), lifespan and DEE (LSR: F1,90 = 0.33, P = 0.57; b = 1.1; Fig. 2b) or lifespan and TAEE (LSR: F1,90 = 2.11, P = 0.15; b = 2.9; Fig. 2c). However, there was a significant negative relationship between RMR and lifespan (LSR: F1,90 = 4.52, P = 0.036; b = −10.7; Fig. 2d). We sorted the data set for each variable from the lowest to the highest values of BM, DEE, TAEE and RMR and divided them into two groups for each trait: high and low. We then plotted mortality curves for the divided data and analysed the data in two ways: first comparing the mean lifespan of the two groups using t tests and then analysing the mortality rates using the Kaplan–Meier analysis. These results corroborate those obtained by regression analysis on the individual values. There was no significant difference in lifespan between animals with low and high body mass (mean SE lifespan, 635 ± 21 and 630 ± 22 days, respectively; t test, P = 0.87). Mortality rate comparisons performed using Kaplan–Meier analysis of survival revealed no difference between the two groups (log-rank Mantel–Cox χ2, P = 0.86; n = 92; Fig. 3a). There was no significant difference in lifespan between animals with low and high DEE (mean SE lifespan, 628 ± 22 and 637 ± 20 days, respectively; t test, P = 0.77) with no difference in mortality rate between the two groups of DEE (log-rank χ2, P = 0.96; Fig. 3b; n = 92). Also, we found no difference between mean lifespan for comparison between low and high TAEE animals (mean ± SE lifespan, 632 ± 23 and 633 ± 20 days, respectively; t test P = 0.97) and no difference in mortality rate between the two groups (χ2, P = 0.76; Fig. 3c; n = 92). The comparison between RMR longevity curves confirmed that animals with low RMR (mean ± SE lifespan, 662 ± 22 days) lived longer than mice with high RMR (603 ± 20 days; t test: P = 0.047) by about 10 %. Kaplan–Meier analysis of survival revealed a significant difference in mortality rate between the two groups (log-rank Mantel χ2 = 4.9, P = 0.027; Fig. 3d; n = 92).Fig. 2


Low resting metabolic rate is associated with greater lifespan because of a confounding effect of body fatness.

Duarte LC, Speakman JR - Age (Dordr) (2014)

Survival curves. Cumulative survival curve (Kaplan–Meier survival plot) of female MF1 mice. The cumulative survival rate was plotted against age in days. Log-rank test was performed to compare high and low body mass (a), daily energy expenditure (b), thermoregulatory activity energy expenditure (c) and resting metabolic rate (d) (see text for statistics)
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Related In: Results  -  Collection

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Fig3: Survival curves. Cumulative survival curve (Kaplan–Meier survival plot) of female MF1 mice. The cumulative survival rate was plotted against age in days. Log-rank test was performed to compare high and low body mass (a), daily energy expenditure (b), thermoregulatory activity energy expenditure (c) and resting metabolic rate (d) (see text for statistics)
Mentions: In the selected sample of 92 individuals that were retained for lifespan analysis, there was no significant relationship between lifespan and body mass (least squares linear regression analysis (LSR): F1,90 = 0.02, P = 0.90; b = −0.4; Fig. 2a), lifespan and DEE (LSR: F1,90 = 0.33, P = 0.57; b = 1.1; Fig. 2b) or lifespan and TAEE (LSR: F1,90 = 2.11, P = 0.15; b = 2.9; Fig. 2c). However, there was a significant negative relationship between RMR and lifespan (LSR: F1,90 = 4.52, P = 0.036; b = −10.7; Fig. 2d). We sorted the data set for each variable from the lowest to the highest values of BM, DEE, TAEE and RMR and divided them into two groups for each trait: high and low. We then plotted mortality curves for the divided data and analysed the data in two ways: first comparing the mean lifespan of the two groups using t tests and then analysing the mortality rates using the Kaplan–Meier analysis. These results corroborate those obtained by regression analysis on the individual values. There was no significant difference in lifespan between animals with low and high body mass (mean SE lifespan, 635 ± 21 and 630 ± 22 days, respectively; t test, P = 0.87). Mortality rate comparisons performed using Kaplan–Meier analysis of survival revealed no difference between the two groups (log-rank Mantel–Cox χ2, P = 0.86; n = 92; Fig. 3a). There was no significant difference in lifespan between animals with low and high DEE (mean SE lifespan, 628 ± 22 and 637 ± 20 days, respectively; t test, P = 0.77) with no difference in mortality rate between the two groups of DEE (log-rank χ2, P = 0.96; Fig. 3b; n = 92). Also, we found no difference between mean lifespan for comparison between low and high TAEE animals (mean ± SE lifespan, 632 ± 23 and 633 ± 20 days, respectively; t test P = 0.97) and no difference in mortality rate between the two groups (χ2, P = 0.76; Fig. 3c; n = 92). The comparison between RMR longevity curves confirmed that animals with low RMR (mean ± SE lifespan, 662 ± 22 days) lived longer than mice with high RMR (603 ± 20 days; t test: P = 0.047) by about 10 %. Kaplan–Meier analysis of survival revealed a significant difference in mortality rate between the two groups (log-rank Mantel χ2 = 4.9, P = 0.027; Fig. 3d; n = 92).Fig. 2

Bottom Line: Fat-free mass (FFM) and fat mass (FM) were both significantly positively related to RMR.After removing the effect of FFM on RMR, the association between RMR and lifespan remained significantly negative; however, after statistically removing the effect of FM on RMR, the significant association between RMR and lifespan disappeared.We conclude that the negative association between RMR and lifespan is primarily due to the effect of FM, with FM positively related to both RMR and mortality and hence RMR negatively to lifespan.

View Article: PubMed Central - PubMed

Affiliation: Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK, l.duarte@abdn.ac.uk.

ABSTRACT
A negative association between resting metabolic rate (RMR) and lifespan is the cornerstone of the rate of living and free-radical damage theories of aging. Empirical studies supporting a negative association of RMR to lifespan may arise from the correlation between RMR and both daily energy expenditure (DEE) and thermoregulatory activity energy expenditure (TAEE). We screened 540 female mice for higher and lower DEE and measured RMR in the resulting 324 (60 %). We then selected 92 mice in which there was no link between residual from the regression of RMR against body mass (BM) and residual of DEE against BM to separate the effects of these traits. Lifespan was not significantly related to body mass, DEE and TAEE, but significantly negatively related to RMR. Fat-free mass (FFM) and fat mass (FM) were both significantly positively related to RMR. After removing the effect of FFM on RMR, the association between RMR and lifespan remained significantly negative; however, after statistically removing the effect of FM on RMR, the significant association between RMR and lifespan disappeared. We conclude that the negative association between RMR and lifespan is primarily due to the effect of FM, with FM positively related to both RMR and mortality and hence RMR negatively to lifespan. In 40 additional screened mice, greater FM was also associated with greater oxidative damage to DNA.

Show MeSH
Related in: MedlinePlus