The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Lifelong restriction of dietary branched-chain amino acids has sex-specific benefits for frailty and life span in mice
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Several studies have shown that restriction of protein or specific restriction of either methionine or one or more of the branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) reduces mTORC1 activity and extends lifespan in preclinical species 24,150–152.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [152]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Frailty in Older Adults: Evidence for a Phenotype
Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., Seeman, T., Tracy, R., Kop, W. J., Burke, G., et al. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.3.m146 · Cited by 24,907
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Accumulation of Deficits as a Proxy Measure of Aging
Mitnitski, A. B., Mogilner, A. J., & Rockwood, K. (2001) · The Scientific World JOURNAL · doi:10.1100/tsw.2001.58 · Cited by 2,893
Sestrin2 is a leucine sensor for the mTORC1 pathway
Wolfson, R. L., Chantranupong, L., Saxton, R. A., Shen, K., Scaria, S. M., Cantor, J. R., & Sabatini, D. M. (2016) · Science · doi:10.1126/science.aab2674 · Cited by 1,306
Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120
Influence of TOR kinase on lifespan in C. elegans
Vellai, T., Takacs-Vellai, K., Zhang, Y., Kovacs, A. L., Orosz, L., & Müller, F. (2003) · Nature · doi:10.1038/426620a · Cited by 1,057
Solon-Biet, S. M., McMahon, A. C., Ballard, J. W. O., Ruohonen, K., Wu, L. E., Cogger, V. C., Warren, A., Huang, X., Pichaud, N., Melvin, R. G., et al. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.009 · Cited by 904
The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway
Chantranupong, L., Scaria, S. M., Saxton, R. A., Gygi, M. P., Shen, K., Wyant, G. A., Wang, T., Harper, J. W., Gygi, S. P., & Sabatini, D. M. (2016) · Cell · doi:10.1016/j.cell.2016.02.035 · Cited by 843
FGF21 is an endocrine signal of protein restriction
Laeger, T., Henagan, T. M., Albarado, D. C., Redman, L. M., Bray, G. A., Noland, R. C., Münzberg, H., Hutson, S. M., Gettys, T. W., Schwartz, M. W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74915 · Cited by 593
D'Antona, G., Ragni, M., Cardile, A., Tedesco, L., Dossena, M., Bruttini, F., Caliaro, F., Corsetti, G., Bottinelli, R., Carruba, M. O., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.08.016 · Cited by 568
Flagged first, then by citations
Research works printed but not linked: 77
- Weindruch, R., Walford, R. L., Fligiel, S. & Guthrie, D. The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr. 116, 641–654 (1986). · DOI
- Cummings, N. E. & Lamming, D. W. Regulation of metabolic health and aging by nutrient-sensitive signaling pathways. Mol. Cell. Endocrinol. 455, 13–22 (2017). · DOI
- Solon-Biet, S. M. et al. Macronutrients and caloric intake in health and longevity. J. Endocrinol. 226, R17–R28 (2015). · DOI
- Green, C. L. & Lamming, D. W. Regulation of metabolic health by essential dietary amino acids. Mech. Ageing Dev. 177, 186–200 (2019). · DOI
- Gannon, M. C., Nuttall, F. Q., Saeed, A., Jordan, K. & Hoover, H. An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes. Am. J. Clin. Nutr. 78, 734–741 (2003). · DOI · Paper page
- Dong, J. Y., Zhang, Z. L., Wang, P. Y. & Qin, L. Q. Effects of high-protein diets on body weight, glycaemic control, blood lipids and blood pressure in type 2 diabetes: meta-analysis of randomised controlled trials. Br. J. Nutr. 110, 781–789 (2013). · DOI · Paper page
- Seino, Y., Seino, S., Ikeda, M., Matsukura, S. & Imura, H. Beneficial effects of high protein diet in treatment of mild diabetes. Hum. Nutr. Appl. Nutr. 37 A, 226–230 (1983).
- Coelho-Junior H. J., Rodrigues B., Uchida M., Marzetti E. Low protein intake is associated with frailty in older adults: a systematic review and meta-analysis of observational studies. Nutrients 10, 1334 (2018). · DOI
- Coelho-Júnior H. J., et al. Protein-related dietary parameters and frailty status in older community-dwellers across different frailty instruments. Nutrients 12, 508 (2020). · DOI
- Levine, M. E. et al. Low protein intake is associated with a major reduction in IGF-1, cancer and overall mortality in the 65 and younger but not older population. Cell Metab. 19, 407–417 (2014). · DOI · Paper page
- Lagiou, P. et al. Low carbohydrate–high protein diet and mortality in a cohort of Swedish women. J. Intern. Med. 261, 366–374 (2007). · DOI
- Vergnaud, A. C. et al. Macronutrient composition of the diet and prospective weight change in participants of the EPIC-PANACEA study. PLoS ONE 8, e57300 (2013). · DOI
- Fontana, L. et al. Decreased consumption of branched-chain amino acids improves metabolic health. Cell Rep. 16, 520–530 (2016). · DOI · Paper page
- Cummings, N. E. et al. Restoration of metabolic health by decreased consumption of branched-chain amino acids. J. Physiol. 596, 623–645 (2018). · DOI
- Lee, K. P. et al. Lifespan and reproduction in Drosophila: new insights from nutritional geometry. Proc. Natl Acad. Sci. USA 105, 2498–2503 (2008). · DOI · Paper page
- Mair, W., Piper, M. D. & Partridge, L. Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol. 3, e223 (2005). · DOI
- Ross, M. H. Length of life and nutrition in the rat. J. Nutr. 75, 197–210 (1961). · DOI
- Lee, B. C. et al. Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino-acid status. Nat. Commun. 5, 3592 (2014). · DOI
- Grandison, R. C., Piper, M. D. & Partridge, L. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462, 1061–1064 (2009). · DOI
- Juricic, P., Gronke, S. & Partridge, L. Branched-chain amino acids have equivalent effects to other essential amino acids on lifespan and aging-related traits in Drosophila. J. Gerontol. A Biol. Sci. Med. Sci. 75, 24–31 (2020). · DOI
- Yoshida, S. et al. Role of dietary amino acid balance in diet restriction-mediated lifespan extension, renoprotection and muscle weakness in aged mice. Aging Cell 17, e12796 (2018). · DOI
- Miller, R. A. et al. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4, 119–125 (2005). · DOI · Paper page
- Orentreich, N., Matias, J. R., DeFelice, A. & Zimmerman, J. A. Low methionine ingestion by rats extends life span. J. Nutr. 123, 269–274 (1993).
- Brown-Borg, H. M. et al. Growth hormone signaling is necessary for lifespan extension by dietary methionine. Aging Cell 13, 1019–1027 (2014). · DOI
- Ooka, H., Segall, P. E. & Timiras, P. S. Histology and survival in age-delayed low-tryptophan-fed rats. Mech. Ageing. Dev. 43, 79–98 (1988). · DOI
- De Marte, M. L. & Enesco, H. E. Influence of low tryptophan diet on survival and organ growth in mice. Mech. Ageing. Dev. 36, 161–171 (1986). · DOI
- Newgard, C. B. et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 9, 311–326 (2009). · DOI · Paper page
- Batch, B. C. et al. Branched chain amino acids are novel biomarkers for discrimination of metabolic wellness. Metabolism 62, 961–969 (2013). · DOI
- Le Couteur, D. G. et al. Branched chain amino acids, cardiometabolic risk factors and outcomes in older men: the Concord Health and Ageing in Men Project. J. Gerontol. A Biol. Sci. Med. Sci. 75, 1805–1810 (2019). · DOI
- Karusheva, Y. et al. Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial. Am. J. Clin. Nutr. 110, 1098–1107 (2019). · DOI
- White, P. J. et al. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export. Mol. Metab. 5, 538–551 (2016). · DOI
- Solon-Biet, S. M. et al. Branched-chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control. Nat. Metab. 1, 532–545 (2019). · DOI
- Kennedy, B. K. & Lamming, D. W. The Mechanistic Target Of Rapamycin: The Grand ConducTOR of Metabolism and Aging. Cell Metab. 23, 990–1003 (2016). · DOI · Paper page
- Wu, J. J. et al. Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep. 4, 913–920 (2013). · DOI · Paper page
- Kapahi, P. et al. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr. Biol. 14, 885–890 (2004). · DOI · Paper page
- Arriola Apelo, S. I. & Lamming, D. W. Rapamycin: an InhibiTOR of aging emerges from the soil of Easter Island. J. Gerontol. A Biol. Sci. Med. Sci. 71, 841–849 (2016). · DOI
- Wang, C., Li, Q., Redden, D. T., Weindruch, R. & Allison, D. B. Statistical methods for testing effects on “maximum lifespan”. Mech. Ageing Dev. 125, 629–632 (2004). · DOI · Paper page
- Zaghini, A. et al. Long-term breeding of the LmnaG609G progeric mouse: characterization of homozygous and heterozygous models. Exp. Gerontol. 130, 110784 (2020). · DOI
- Whitehead, J. C. et al. A clinical frailty index in aging mice: comparisons with frailty index data in humans. J. Gerontol. A Biol. Sci. Med. Sci. 69, 621–632 (2014). · DOI
- Kane, A. E. et al. Impact of longevity interventions on a validated mouse clinical frailty index. J. Gerontol. A Biol. Sci. Med. Sci. 71, 333–339 (2016). · DOI
- Yousefzadeh M. J., et al. Circulating levels of monocyte chemoattractant protein-1 as a potential measure of biological age in mice and frailty in humans. Aging Cell 17, e12706 (2018). · DOI
- Mitchell, S. E. et al. The effects of graded levels of calorie restriction: impact of short term calorie and protein restriction on circulating hormone levels, glucose homeostasis and oxidative stress in male C57BL/6 mice. Oncotarget 6, 23213–23237 (2015). · DOI
- Chaumontet, C. et al. Low-protein and methionine, high-starch diets increase energy intake and expenditure, increase FGF21, decrease IGF-1 and have little effect on adiposity in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 316, R486–R501 (2019). · DOI · Paper page
- Miller, R. A. et al. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell 13, 468–477 (2014). · DOI
- Mao, K. et al. Late-life targeting of the IGF-1 receptor improves healthspan and lifespan in female mice. Nat. Commun. 9, 2394 (2018). · DOI · Paper page
- Hahn, O. et al. A nutritional memory effect counteracts benefits of dietary restriction in old mice. Nat. Metab. 1, 1059–1073 (2019). · DOI
- Turturro, A. et al. Growth curves and survival characteristics of the animals used in the Biomarkers of Aging Program. J. Gerontol. A Biol. Sci. Med. Sci. 54, B492–B501 (1999). · DOI
- Hu, W. et al. Relationship between branched-chain amino acids, metabolic syndrome and cardiovascular risk profile in a Chinese population: a cross-sectional study. Int. J. Endocrinol. 2016, 8173905 (2016).
- Du, X. et al. Relationships between circulating branched chain amino acid concentrations and risk of adverse cardiovascular events in patients with STEMI treated with PCI. Sci. Rep. 8, 15809 (2018). · DOI
- Wang, W. et al. Defective branche-chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction. Am. J. Physiol. Heart Circ. Physiol. 311, H1160–H1169 (2016). · DOI
- Sun, H. et al. Catabolic defect of branched-chain amino acids promotes heart failure. Circulation 133, 2038–2049 (2016). · DOI
- Chantranupong, L. et al. The sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 9, 1–8 (2014). · DOI · Paper page
- Frock, R. L. et al. Lamin A/C and emerin are critical for skeletal muscle satellite cell differentiation. Genes Dev. 20, 486–500 (2006). · DOI
- Arriola Apelo, S. I. et al. Ovariectomy uncouples lifespan from metabolic health and reveals a sex-hormone-dependent role of hepatic mTORC2 in aging. eLife 9, e56177 (2020). · DOI · Paper page
- Chellappa, K. et al. Hypothalamic mTORC2 is essential for metabolic health and longevity. Aging Cell 18, e13014 (2019). · DOI · Paper page
- Yu, D. et al. Calorie-restriction-induced insulin sensitivity is mediated by adipose mTORC2 and not required for lifespan extension. Cell Rep. 29, 236–248 (2019). · DOI · Paper page
- Sharples, A. P. et al. Longevity and skeletal muscle mass: the role of IGF signalling, the sirtuins, dietary restriction and protein intake. Aging Cell 14, 511–523 (2015). · DOI
- Ericksen, R. E. et al. Loss of BCAA catabolism during carcinogenesis enhances mTORC1 activity and promotes tumor development and progression. Cell Metab. 29, 1151–1165 (2019). · DOI
- Ananieva, E. A. & Wilkinson, A. C. Branched-chain amino acid metabolism in cancer. Curr. Opin. Clin. Nutr. Metab. Care 21, 64–70 (2018). · DOI
- Jensen, K., McClure, C., Priest, N. K. & Hunt, J. Sex-specific effects of protein and carbohydrate intake on reproduction but not lifespan in Drosophila melanogaster. Aging Cell 14, 605–615 (2015). · DOI
- Larson, K. R. et al. Sex differences in the hormonal and metabolic response to dietary protein dilution. Endocrinology 158, 3477–3487 (2017). · DOI · Paper page
- Miller, D. S. & Payne, P. R. Longevity and protein intake. Exp. Gerontol. 3, 231–234 (1968). · DOI
- Barrington, W. T. et al. Improving metabolic health through precision dietetics in mice. Genetics 208, 399–417 (2018). · DOI
- Sittig, L. J. et al. Genetic background limits generalizability of genotype–phenotype relationships. Neuron 91, 1253–1259 (2016). · DOI
- Baar, E. L., Carbajal, K. A., Ong, I. M. & Lamming, D. W. Sex- and tissue-specific changes in mTOR signaling with age in C57BL/6J mice. Aging Cell 15, 155–166 (2016). · DOI · Paper page
- Joseph, G. A. et al. Partial inhibition of mTORC1 in aged rats counteracts the decline in muscle mass and reverses molecular signaling associated with sarcopenia. Mol. Cell. Biol. 39, e00141 (2019). · DOI · Paper page
- Zhou, M. et al. Targeting BCAA catabolism to treat obesity-associated insulin resistance. Diabetes 68, 1730–1746 (2019). · DOI
- Stephenson E. J., et al. Skeletal muscle mTORC1 activation increases energy expenditure and reduces longevity in mice. Preprint at bioRxiv https://doi.org/10.1101/720540720540 (2019). · DOI
- Dai, D. F. et al. Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart. Aging Cell 13, 529–539 (2014). · DOI
- Flynn, J. M. et al. Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell 12, 851–862 (2013). · DOI
- Sullivan, T. et al. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol. 147, 913–920 (1999). · DOI
- Harris, S. P. et al. Hypertrophic cardiomyopathy in cardiac myosin binding protein-C knockout mice. Circ. Res. 90, 594–601 (2002). · DOI
- Zerbino, D. R. et al. Ensembl 2018. Nucleic Acids Res. 46, D754–D761 (2018). · DOI · Paper page
- Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2009). · DOI · Paper page
- Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47 (2015). · DOI · Paper page
- Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Stat. Soc. Series B Stat. Methodol. 57, 289–300 (1995). · DOI · Paper page
- Liang, H. et al. Genetic mouse models of extended lifespan. Exp. Gerontol. 38, 1353–1364 (2003). · DOI
Cited by
Sorted by citations
Molecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714
Self-citationTargeting the biology of aging with mTOR inhibitors
Mannick, J. B., & Lamming, D. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00416-y · Cited by 372
Self-citationHill, C. M., Albarado, D. C., Coco, L. G., Spann, R. A., Khan, M. S., Qualls-Creekmore, E., Burk, D. H., Burke, S. J., Collier, J. J., Yu, S., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-29499-8 · Cited by 117
Host and microbiota metabolic signals in aging and longevity
Zhou, Y., Hu, G., & Wang, M. C. (2021) · Nature Chemical Biology · doi:10.1038/s41589-021-00837-z · Cited by 70
Resistance exercise protects mice from protein-induced fat accretion
Trautman, M. E., Braucher, L. N., Elliehausen, C., Zhu, W. G., Zelenovskiy, E., Green, M., Sonsalla, M. M., Yeh, C.-Y., Hornberger, T. A., Konopka, A. R., et al. (2023) · eLife · doi:10.7554/elife.91007 · Cited by 8
Self-citation
Metadata
- Authors
- Richardson, N. E., Konon, E. N., Schuster, H. S., Mitchell, A. T., Boyle, C., Rodgers, A. C., Finke, M., Haider, L. R., Yu, D., Flores, V., Pak, H. H., Ahmad, S., Ahmed, S., Radcliff, A., Wu, J., Williams, E. M., Abdi, L., Sherman, D. S., Hacker, T. A., & Lamming, D. W.
- Venue
- Nature Aging
- Published
- 2021-01-14
- Volume
- 1
- Issue
- 1
- Pages
- 73-86
- ISSN
- 2662-8465
- PMC
- PMC8009080
- Cited by
- 267
- References
- 23
- Language
- en
- Licence
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute on Aging (AG051974, AG056771-01A1S1, AG066311, AG041765, AG041765, AG050135, AG051974, AG056771, AG062328)
- American Heart Association (17PRE33410983)
- UW | School of Medicine and Public Health, University of Wisconsin-Madison
- Glenn Foundation for Medical Research
- American Federation for Aging Research
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review