β-hydroxy-β-methylbutyrate Attenuates Age-Dependent Loss of Flight Ability and Extends Lifespan in Drosophila
Abstract
1. Introduction
2. Results
2.1. HMB Supplementation Attenuates Aging-Associated Loss of Flight Ability
2.2. HMB Supplementation Extends Lifespan in D. melanogaster
2.3. HMB Supplementation Does Not Alter Feeding Behavior
2.4. HMB Supplementation Confers No Resistance to Oxidative Stress
2.4.1. Resistance to Paraquat Stress
2.4.2. Resistance to Hydrogen Peroxide
2.5. HMB Supplementation Improves Mitochondrial Morphology in Aging Flies
2.6. HMB Supplementation Does Not Improve Citrate Synthase Activity in Aging Flies
3. Discussion
4. Materials and Methods
4.1. D. melanogaster Rearing and Lifespan Assay
4.2. Flight Performance
4.3. Body Weight Measurements
4.4. CAFE Assay
4.5. Stress-Resistance Assay
4.6. Electron Microscopy
4.7. Image Analysis
4.8. Citrate Synthase Assay
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
BCAA | branched-chain amino acid |
CI | confidence interval |
CSY medium | cornmeal, sugar, and yeast medium |
HMB | -hydroxy- -methylbutyrate |
IFM | indirect flight muscle |
TOR | target of rapamycin |
Appendix A
Diet | Flight Score (±SE) | Age |
---|---|---|
Normal | 5.52 (±0.388) | 1 week |
HMB | 5.84 (±0.098) | 1 week |
Normal | 5.12 (±0.15) | 2 week |
HMB | 5.68 (±0.08) | 2 week |
Normal | 3.84 (±0.776) | 3 week |
HMB | 5.52 (±0.196) | 3 week |
Normal | 2.24 (±0.917) | 4 week |
HMB | 5.28 (±0.32) | 4 week |
Normal | 1.84 (±0.854) | 5 week |
HMB | 5.28 (±0.15) | 5 week |
Normal | 1.92 (±0.496) | 6 week |
HMB | 4.48 (±0.637) | 6 week |
Normal | 0.64 (±0.299) | 7 week |
HMB | 3.04 (±0.765) | 7 week |
Normal | 0.2 (±0.2) | 8 week |
HMB | 1.3 (±0.889) | 8 week |
Normal | 0 (±0) | 9 week |
HMB | 0 (±0) | 9 week |
Diet | Flight Score (±SE) | Age |
---|---|---|
Normal | 5.76 (±0.16) | 1 Week |
HMB | 5.76 (±0.098) | 1 Week |
Normal | 4.5 (±0.576) | 2 Week |
HMB | 5.6 (±0.126) | 2 Week |
Normal | 4.08 (±0.774) | 3 Week |
HMB | 5.44 (±0.299) | 3 Week |
Normal | 2.72 (±0.388) | 4 Week |
HMB | 5.28 (±0.528) | 4 Week |
Normal | 1.12 (±0.637) | 5 Week |
HMB | 4.4 (±0.716) | 5 Week |
Normal | 0 (±0) | 6 Week |
HMB | 3.28 (±0.916) | 6 Week |
Normal | 0 (±0) | 7 Week |
HMB | 0.88 (±0.388) | 7 Week |
Normal | 0 (±0) | 8 Week |
HMB | 0 (±0) | 8 Week |
Normal | 0 (±0) | 9 Week |
HMB | 0 (±0) | 9 Week |
Term | Contrast | Adj p Value |
---|---|---|
Adult Diet | Normal-HMB | 7.59 × 10−1 |
Age | 4 Week old-1 Week old | 8.89 × 10−6 |
Adult Diet:Age | Normal:1 Week old-HMB:1 Week old | 8.88 × 10−1 |
Adult Diet:Age | HMB:4 Week old-HMB:1 Week old | 7.82 × 10−4 |
Adult Diet:Age | Normal:4 Week old-HMB:1 Week old | 2.66 × 10−3 |
Adult Diet:Age | HMB:4 Week old-Normal:1 Week old | 1.17 × 10−3 |
Adult Diet:Age | Normal:4 Week old-Normal:1 Week old | 2.54 × 10−3 |
Adult Diet:Age | Normal:4 Week old-HMB:4 Week old | 9.92 × 10−1 |
Term | Contrast | Adj p Value |
---|---|---|
Adult Diet:Age | Normal:1 Week old-HMB:1 Week old | 9.448580 × 10−1 |
Adult Diet:Age | HMB:4 Week old-HMB:1 Week old | 3.093000 × 10−4 |
Adult Diet:Age | Normal:4 Week old-HMB:1 Week old | 2.264880 × 10−2 |
Adult Diet:Age | HMB:4 Week old-Normal:1 Week old | 5.646400 × 10−3 |
Adult Diet:Age | Normal:4 Week old-Normal:1 Week old | 1.209837 × 10−1 |
Adult Diet:Age | Normal:4 Week old-HMB:4 Week old | 5.878281 × 10−1 |
Term | Contrast | Adj p Value |
---|---|---|
Adult Diet | Normal-HMB | 5.82 × 10−1 |
Age | 4 Week old-1 Week old | 5.25 × 10−8 |
Adult Diet:Age | Normal:1 Week old-HMB:1 Week old | 1.77 × 10−1 |
Adult Diet:Age | HMB:4 Week old-HMB:1 Week old | 2.84 × 10−5 |
Adult Diet:Age | Normal:4 Week old-HMB:1 Week old | 2.51 × 10−5 |
Adult Diet:Age | HMB:4 Week old-Normal:1 Week old | 7.6 × 10−6 |
Adult Diet:Age | Normal:4 Week old-Normal:1 Week old | 6.3 × 10−6 |
Adult Diet:Age | Normal:4 Week old-HMB:4 Week old | 5.29 × 10−1 |
Term | Contrast | Adj p Value |
---|---|---|
Adult Diet | Normal-HMB | 2.14 × 10−1 |
Age | 4 Week old-1 Week old | 4.00 × 10−3 |
Adult Diet:Age | Normal:1 Week old-HMB:1 Week old | 9.63 × 10−1 |
Adult Diet:Age | HMB:4 Week old-HMB:1 Week old | 3.30 × 10−2 |
Adult Diet:Age | Normal:4 Week old-HMB:1 Week old | 6.40 × 10−1 |
Adult Diet:Age | HMB:4 Week old-Normal:1 Week old | 3.90 × 10−2 |
Adult Diet:Age | Normal:4 Week old-Normal:1 Week old | 4.93 × 10−1 |
Adult Diet:Age | Normal:4 Week old-HMB:4 Week old | 5.40 × 10−1 |
Term | DF | SUMSQ | MEANSQ | Statistic | p Value |
---|---|---|---|---|---|
Adult Diet | 1 | 0.02 | 0.02 | 0.10 | 7.59 × 10−1 |
Age | 1 | 11.47 | 11.47 | 45.95 | 8.89 × 10−6 |
Adult Diet:Age | 1 | 0.12 | 0.12 | 0.49 | 4.94 × 10−1 |
Residuals | 14 | 3.49 | 0.25 | NA | NA |
Term | DF | SUMSQ | MEANSQ | Statistic | p Value |
---|---|---|---|---|---|
Adult Diet | 1 | 0.09 | 0.09 | 0.27 | 6.13 × 10−1 |
Age | 1 | 12.43 | 12.43 | 36.06 | 3.23 × 10−5 |
Adult Diet:Age | 1 | 0.58 | 0.58 | 1.68 | 2.16 × 10−1 |
Residuals | 14 | 4.82 | 0.34 | NA | NA |
Term | DF | SUMSQ | MEANSQ | Statistic | p Value |
---|---|---|---|---|---|
Adult Diet | 1 | 0.03 | 0.03 | 0.32 | 5.82 × 10−1 |
Age | 1 | 9.08 | 9.08 | 109.69 | 5.25 × 10−8 |
Adult Diet:Age | 1 | 0.52 | 0.52 | 6.34 | 2.46 × 10−2 |
Residuals | 14 | 1.16 | 0.08 | NA | NA |
Term | DF | SUMSQ | MEANSQ | Statistic | p Value |
---|---|---|---|---|---|
Adult Diet | 1 | 0.22 | 0.22 | 1.69 | 0.21418 |
Age | 1 | 1.49 | 1.49 | 11.52 | 0.00436 |
Adult Diet:Age | 1 | 0.05 | 0.05 | 0.39 | 0.53997 |
Residuals | 14 | 1.82 | 0.13 | NA | NA |
Term | DF | SUMSQ | MEANSQ | Statistic | p Value |
---|---|---|---|---|---|
Age | 1 | 0.02 | 0.02 | 14.57 | 0.00411 |
Adult Diet | 1 | 0.00 | 0.00 | 1.62 | 0.23514 |
Residuals | 9 | 0.01 | 0.00 | NA | NA |
Term | DF | SUMSQ | MEANSQ | Statistic | p Value |
---|---|---|---|---|---|
Age | 1 | 0.10 | 0.1 | 99.74 | 3.62 × 10−6 |
Adult Diet | 1 | 0.00 | 0.0 | 3.13 | 1.11 × 10−1 |
Residuals | 9 | 0.01 | 0.0 | NA | NA |
Term | DF | SUMSQ | MEANSQ | Statistic | p Value |
---|---|---|---|---|---|
Age | 1 | 0.10 | 0.1 | 33.94 | 0.000251 |
Adult Diet | 1 | 0.00 | 0.0 | 0.03 | 0.873853 |
Residuals | 9 | 0.03 | 0.0 | NA | NA |
Term | DF | SUMSQ | MEANSQ | Statistic | p Value |
---|---|---|---|---|---|
Age | 1 | 0.01 | 0.01 | 0.44 | 0.522 |
Adult Diet | 1 | 0.00 | 0.00 | 0.06 | 0.816 |
Residuals | 9 | 0.18 | 0.02 | NA | NA |
Term | Contrast | Null.Value | Estimate | Conf.Low | Conf.High | Adj p Value |
---|---|---|---|---|---|---|
Diet | Normal-HMB | 0 | 0.66 | 0.43 | 0.89 | 2.07 × 10−8 |
Age | 6 week-1 week | 0 | 0.21 | −0.02 | 0.44 | 0.06905 |
Diet:Age | Normal:1 week-HMB:1 week | 0 | 0.09 | −0.37 | 0.54 | 0.961 |
Diet:Age | HMB:6 week-HMB:1 week | 0 | −0.26 | −0.74 | 0.22 | 0.501 |
Diet:Age | Normal:6 week-HMB:1 week | 0 | 0.82 | 0.46 | 1.18 | 3.1 × 10−8 |
Diet:Age | HMB:6 week-Normal:1 week | 0 | −0.35 | −0.91 | 0.21 | 0.38 |
Diet:Age | Normal:6 week-Normal:1 week | 0 | 0.73 | 0.27 | 1.19 | 2.49 × 10−4 |
Diet:Age | Normal:6 week-HMB:6 week | 0 | 1.08 | 0.60 | 1.56 | 6.5 × 10−8 |
Term | Contrast | Null.Value | Estimate | Conf.Low | Conf.High | Adj p Value |
---|---|---|---|---|---|---|
Diet | Normal-HMB | 0 | 0.89 | 0.64 | 1.14 | 7.19 × 10−11 |
Age | 6 week-1 week | 0 | 0.46 | 0.23 | 0.69 | 8.91 × 10−5 |
Diet:Age | Normal:1 week-HMB:1 week | 0 | 0.15 | −0.40 | 0.70 | 0.9033 |
Diet:Age | HMB:6 week-HMB:1 week | 0 | −0.45 | −1.04 | 0.15 | 0.2089 |
Diet:Age | Normal:6 week-HMB:1 week | 0 | 0.93 | 0.40 | 1.46 | 4.657 × 10−5 |
Diet:Age | HMB:6 week-Normal:1 week | 0 | −0.60 | −1.03 | -0.16 | 2.675 × 10−3 |
Diet:Age | Normal:6 week-Normal:1 week | 0 | 0.78 | 0.43 | 1.14 | 6.9026 × 10−8 |
Diet:Age | Normal:6 week-HMB:6 week | 0 | 1.38 | 0.96 | 1.80 | 6.43 × 10−11 |
Age | Diet | Variable | n | Mean | Median | S.E |
---|---|---|---|---|---|---|
1 week | HMB | Area | 201.00 | 2.51 | 2.25 | 0.10 |
1 week | Normal | Area | 661.00 | 2.66 | 2.30 | 0.07 |
6 week | HMB | Area | 384.00 | 2.06 | 1.72 | 0.07 |
6 week | Normal | Area | 874.00 | 3.44 | 2.34 | 0.12 |
Age | Diet | Variable | n | Mean | Median | S.E |
---|---|---|---|---|---|---|
1 week | HMB | Area | 497.00 | 2.62 | 2.31 | 0.07 |
1 week | Normal | Area | 215.00 | 2.71 | 1.89 | 0.16 |
6 week | HMB | Area | 186.00 | 2.36 | 1.98 | 0.12 |
6 week | Normal | Area | 471.00 | 3.44 | 2.75 | 0.12 |
Age | Axes | Group1 | Group2 | n1 | n2 | Statistic | df | p | p.adj |
---|---|---|---|---|---|---|---|---|---|
1 week | Major | HMB | Normal | 111 | 69 | −7.30 | 110.55 | 0.00 | 0.00 |
6 weeks | Major | HMB | Normal | 102 | 104 | −6.77 | 147.41 | 0.00 | 0.00 |
1 week | Minor | HMB | Normal | 111 | 69 | −0.33 | 132.19 | 0.74 | 0.74 |
6 weeks | Minor | HMB | Normal | 102 | 104 | −2.80 | 153.80 | 0.01 | 0.01 |
Age | Axes | Group1 | Group2 | n1 | n2 | Statistic | df | p | p.adj |
---|---|---|---|---|---|---|---|---|---|
1 week | Major | HMB | Normal | 111 | 69 | −7.30 | 110.55 | 0.00 | 0.00 |
6 weeks | Major | HMB | Normal | 102 | 104 | −6.77 | 147.41 | 0.00 | 0.00 |
1 week | Minor | HMB | Normal | 111 | 69 | −0.33 | 132.19 | 0.74 | 0.74 |
6 weeks | Minor | HMB | Normal | 102 | 104 | −2.80 | 153.80 | 0.01 | 0.01 |
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Nagori, R.; Vigoreaux, J.O. β-hydroxy-β-methylbutyrate Attenuates Age-Dependent Loss of Flight Ability and Extends Lifespan in Drosophila. Int. J. Mol. Sci. 2025, 26, 2664. https://doi.org/10.3390/ijms26062664
Nagori R, Vigoreaux JO. β-hydroxy-β-methylbutyrate Attenuates Age-Dependent Loss of Flight Ability and Extends Lifespan in Drosophila. International Journal of Molecular Sciences. 2025; 26(6):2664. https://doi.org/10.3390/ijms26062664
Chicago/Turabian StyleNagori, Ravi, and Jim O. Vigoreaux. 2025. "β-hydroxy-β-methylbutyrate Attenuates Age-Dependent Loss of Flight Ability and Extends Lifespan in Drosophila" International Journal of Molecular Sciences 26, no. 6: 2664. https://doi.org/10.3390/ijms26062664
APA StyleNagori, R., & Vigoreaux, J. O. (2025). β-hydroxy-β-methylbutyrate Attenuates Age-Dependent Loss of Flight Ability and Extends Lifespan in Drosophila. International Journal of Molecular Sciences, 26(6), 2664. https://doi.org/10.3390/ijms26062664