SIRT1/3/6 Landscape of Human Longevity: A Sex- and Health-Stratified Pilot Study
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Sample Collection
2.3. Immunofluorescent Staining
2.4. Image Quantification
2.5. Morphometric Analysis
2.6. RNA Extraction and Quantitative Real-Time PCR
2.7. Statistical Analysis
3. Results
3.1. Age-Dependent Dynamics of Expression and Translational Efficiency of SIRT1, SIRT3, and SIRT6
3.2. Sex-Dependent Dynamics of Expression and Translational Efficiency of SIRT1, SIRT3, and SIRT6
3.3. Health Status Correlation
4. Discussion
5. Conclusions
6. Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- United Nations, Department of Economic and Social Affairs, Population Division. World Population Ageing 2019: Highlights (ST/ESA/SER.A/430); United Nations: New York, NY, USA, 2019. [Google Scholar]
- Gilleard, C.; Higgs, P. The Third Age and the Baby Boomers: Two Approaches to the Social Structuring of Later Life. Int. J. Ageing Later Life 2007, 2, 5–25. [Google Scholar] [CrossRef]
- North, R.M.; Winters, M.; Clarke, P.J. Cohort effects on self-rated health in the Lausanne Cohort 65+ Study. Age Ageing 2018, 47, 564–571. [Google Scholar]
- World Health Organization. Decade of Healthy Ageing 2021–2030; World Health Organization: Geneva, Switzerland, 2020; Available online: https://www.who.int/initiatives/decade-of-healthy-ageing (accessed on 6 August 2025).
- Kennedy, B.K.; Berger, S.L.; Brunet, A.; Campisi, J.; Cuervo, A.M.; Epel, E.S.; Franceschi, C.; Lithgow, G.J.; Morimoto, R.I.; Pessin, J.E.; et al. Geroscience: Linking Aging to Chronic Diease. Cell 2014, 159, 709–713. [Google Scholar] [CrossRef]
- Ramirez, C.; Smith, P. Climbing the longevity pyramid: Overview of evidence-driven healthcare prevention strategies for human longevity. Front. Aging 2024, 5, 1495029. [Google Scholar] [CrossRef] [PubMed]
- Kuznetsova, S.M.; Kamilova, N.M.; Aliev, R.; Hashimova, U.F. Mechanisms of Longevity Phenomenon in Azerbaijan. J. Gerontol. Geriatr. Med. 2016, 2, 011. [Google Scholar] [CrossRef]
- State Statistical Committee of the Republic of Azerbaijan. Population by Age Group, 2020 and 2024; State Statistical Committee of the Republic of Azerbaijan: Baku, Azerbaijan, 2025. Available online: https://www.stat.gov.az/source/demoqraphy/ap/ (accessed on 6 August 2025).
- Rashidova, A.M.; Hashimova, U.F.; Gadimova, Z.M. Study of Energy-Metabolism Enzymes and the State of the Cardiovascular System in Elderly and Senile-Aged Patients. Adv. Gerontol. 2020, 10, 86–93. [Google Scholar] [CrossRef]
- Guo, J.; Huang, X.; Dou, L.; Yan, M.; Shen, T.; Tang, W.; Li, J. Aging and aging-related diseases: From molecular mechanisms to interventions and treatments. Signal Transduct. Target. Ther. 2022, 7, 391. [Google Scholar] [CrossRef]
- Li, Y.; Tian, X.; Luo, J.; Bao, T.; Wang, S.; Wu, X. Molecular mechanisms of aging and anti-aging strategies. Cell Commun. Signal. 2024, 22, 285. [Google Scholar] [CrossRef]
- Frankowska, N.; Bryl, E.; Fulop, T.; Witkowski, J.M. Longevity, Centenarians and Modified Cellular Proteodynamics. Int. J. Mol. Sci. 2023, 24, 2888. [Google Scholar] [CrossRef]
- Medawar, P.B. An Unsolved Problem of Biology; H. K. Lewis: London, UK, 1952; Available online: https://archive.org/details/medawar-1952-unsolved-problem (accessed on 6 August 2025).
- Harman, D. Aging: A theory based on free radical and radiation chemistry. J. Gerontol. 1956, 11, 298–300. [Google Scholar] [CrossRef]
- Harman, D. The biologic clock: The mitochondria? J. Am. Geriatr. Soc. 1972, 20, 145–147. [Google Scholar] [CrossRef]
- Williams, G.C. Pleiotropy, natural selection, and the evolution of senescence. Evolution 1957, 11, 398–411. [Google Scholar] [CrossRef]
- Kirkwood, T.B.L. Evolution of ageing. Nature 1977, 270, 301–304. [Google Scholar] [CrossRef]
- Morimoto, R.I.; Cuervo, A.M. Proteostasis and the aging proteome in health and disease. J. Gerontol. A Biol. Sci. Med. Sci. 2014, 69, S33–S38. [Google Scholar] [CrossRef]
- Blagosklonny, M.V. Aging and immortality: Quasi-programmed senescence and its pharmacologic inhibition. Cell Cycle 2006, 5, 2087–2102. [Google Scholar] [CrossRef]
- Wang, J.; Michelitsch, T. Aging as a process of accumulation of Misrepairs. arXiv 2015, arXiv:1503.07163. Available online: https://arxiv.org/abs/1503.07163 (accessed on 6 August 2025).
- Sinclair, D.A.; LaPlante, M.D. Lifespan: Why We Age—And Why We Don’t Have to; Atria Books: New York, NY, USA, 2019. [Google Scholar]
- Yang, J.-H.; Petty, C.A.; Dixon-McDougall, T.; Lopez, M.V.; Tyshkovskiy, A.; Maybury-Lewis, S.; Tian, X.; Ibrahim, N.; Chen, Z.; Griffin, P.T.; et al. Chemically induced reprogramming to reverse cellular aging. Aging 2023, 15, 5209–5227. [Google Scholar] [CrossRef] [PubMed]
- López-Otín, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. Hallmarks of aging: An expanding universe. Cell 2023, 186, 243–278. [Google Scholar] [CrossRef] [PubMed]
- Rajendran, R.; Garva, R.; Krstic-Demonacos, M.; Demonacos, C. Sirtuins: Molecular traffic lights in the crossroad of oxidative stress, chromatin remodeling, and transcription. J. Biomed. Biotechnol. 2011, 2011, 368276. [Google Scholar] [CrossRef] [PubMed]
- Hall, J.A.; Dominy, J.E.; Lee, Y.; Puigserver, P. The sirtuin family’s role in aging and age-associated pathologies. J. Clin. Invest. 2013, 123, 973–979. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Bonkowski, M.S.; Sinclair, D.A. Slowing ageing by design: The rise of NAD+ and sirtuin-activating compounds. Nat. Rev. Mol. Cell Biol. 2016, 17, 679–690. [Google Scholar] [CrossRef] [PubMed]
- Wu, Q.-J.; Zhang, T.-N.; Chen, H.-H.; Yu, X.-F.; Lv, J.-L.; Liu, Y.-Y.; Liu, Y.-S.; Zheng, G.; Zhao, J.-Q.; Wei, Y.-F.; et al. The sirtuin family in health and disease. Sig. Transduct. Target. Ther. 2022, 7, 402. [Google Scholar] [CrossRef] [PubMed]
- Zhao, L.; Cao, J.; Hu, K.; He, X.; Yun, D.; Tong, T.; Han, L. Sirtuins and their Biological Relevance in Aging and Age-Related Diseases. Aging Dis. 2020, 11, 927–945. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Kosciuk, T.; Wang, M.; Hong, J.Y.; Lin, H. Updates on the epigenetic roles of sirtuins. Curr. Opin. Chem. Biol. 2019, 51, 18–29. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Mostoslavsky, R.; Chua, K.F.; Lombard, D.B.; Pang, W.W.; Fischer, M.R.; Gellon, L.; Liu, P.; Mostoslavsky, G.; Franco, S.; Murphy, M.M.; et al. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell 2006, 124, 315–329. [Google Scholar] [CrossRef]
- Kane, A.E.; Sinclair, D.A. Sirtuins and NAD+ in the development and treatment of metabolic and cardiovascular diseases. Circ. Res. 2018, 123, 868–885. [Google Scholar] [CrossRef]
- TenNapel, M.J.; Lynch, C.F.; Burns, T.L.; Wallace, R.; Smith, B.J.; Button, A.; Domann, F.E. SIRT6 Minor Allele Genotype Is Associated with >5-Year Decrease in Lifespan in an Aged Cohort. PLoS ONE 2014, 9, e115616. [Google Scholar] [CrossRef]
- Simon, M.; Yang, J.; Gigas, J.; Earley, E.J.; Hillpot, E.; Zhang, L.; Zagorulya, M.; Tombline, G.; Gilbert, M.; Yuen, S.L.; et al. A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A. EMBO J. 2022, 41, e110393. [Google Scholar] [CrossRef]
- Kilic, U.; Gok, O.; Erenberk, U.; Dundaroz, M.R.; Kucukardali, Y.; Elmas, C.; Tufan, E.; Uysal, O. SIRT1 gene variants and longevity in human: A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly. PLoS ONE 2015, 10, e0117954. [Google Scholar] [CrossRef]
- Sah, P.; Rai, A.K.; Syiem, D. Sirtuin activators as an anti-aging intervention for longevity. Explor. Drug Sci. 2025, 3, 100881. [Google Scholar] [CrossRef]
- Grabowska, W.; Sikora, E.; Bielak-Zmijewska, A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology 2017, 18, 447–476. [Google Scholar] [CrossRef]
- Carbone, A.; Linkova, N.; Polyakova, V.; Mironova, E.; Hashimova, U.; Gadzhiev, A.; Safikhanova, K.; Krylova, T.K.J.; Tarquini, R.; Mazzoccoli, G.; et al. Melatonin and Sirtuins in Buccal Epithelium: Potential Biomarkers of Aging and Age-Related Pathologies. Int. J. Mol. Sci. 2020, 21, 8134. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Siddiqui, M.S.; Francois, M.; Rainey-Smith, S.; Martins, R.; Masters, C.L.; Ames, D.; Rowe, C.C.; Macaulay, L.S.; Fenech, M.F.; Leifert, W.R. Evaluation of GammaH2AX in Buccal Cells as a Molecular Biomarker of DNA Damage in Alzheimer’s Disease in the AIBL Study of Ageing. Life 2020, 10, 141. [Google Scholar] [CrossRef] [PubMed]
- Eshkoor, S.A.; Fanijavadi, S. The Environmental Impact on Aging: Insights from Buccal Mucosa and Molecular Biomarkers. Gene Protein Dis. 2024, 3, 4418. [Google Scholar] [CrossRef]
- Argentieri, M.A.; Amin, N.; Nevado-Holgado, A.J.; Sproviero, W.; Collister, J.A.; Keestra, S.M.; Kuliman, M.M.; Ginos, B.N.R.; Ghanbari, M.; Doherty, A.; et al. Integrating the environmental and genetic architectures of aging and mortality. Nat. Med. 2025, 31, 1016–1025. [Google Scholar] [CrossRef]
- Willcox, D.C.; Willcox, B.J.; Hsueh, W.C.; Suzuki, M. Genetic determinants of exceptional human longevity: Insights from the Okinawa Centenarian Study. Age 2006, 28, 313–332. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- You, Y.; Liang, W. SIRT1 and SIRT6: The role in aging-related diseases. Biochim. Biophys. Acta Mol. Basis Dis. 2023, 1869, 166815. [Google Scholar] [CrossRef]
- Brown, K.; Xie, S.; Qiu, X.; Mohrin, M.; Shin, J.; Liu, Y.; Zhang, D.; Scadden, D.T.; Chen, D. SIRT3 reverses aging-associated degeneration. Cell Rep. 2013, 3, 319–327. [Google Scholar] [CrossRef]
- Rogina, B.; Tissenbaum, H.A. SIRT1, resveratrol and aging. Front. Genet. 2024, 15, 1393181. [Google Scholar] [CrossRef]
- Indo, H.P.; Chatatikun, M.; Nakanishi, I.; Matsumoto, K.-i.; Imai, M.; Kawakami, F.; Kubo, M.; Abe, H.; Ichikawa, H.; Yonei, Y.; et al. The Roles of Mitochondria in Human Being’s Life and Aging. Biomolecules 2024, 14, 1317. [Google Scholar] [CrossRef]
- Jia, G.; Su, L.; Singhal, S.; Liu, X. Emerging roles of SIRT6 on telomere maintenance, DNA repair, metabolism and mammalian aging. Mol. Cell Biochem. 2012, 364, 345–350. [Google Scholar] [CrossRef] [PubMed]
- Matsuzaki, T.; Weistuch, C.; de Graff, A.; Dill, K.A.; Balázsi, G. Transcriptional Drift in Aging Cells: A Global De-controller. bioRxiv 2023. bioRxiv: 2023.11.21.568122 Erratum in Proc. Natl. Acad. Sci. USA 2024, 121, e2401830121. [Google Scholar] [CrossRef]
- Llewellyn, J.; Hubbard, S.J.; Swift, J. Translation is an emerging constraint on protein homeostasis in ageing. Trends Cell Biol. 2024, 34, 646–656. [Google Scholar] [CrossRef] [PubMed]
- Ding, Y.; Zuo, Y.; Zhang, B.; Fan, Y.; Xu, G.; Cheng, Z.; Ma, S.; Fang, S.; Tian, A.; Gao, D.; et al. Comprehensive Human Proteome Profiles across a 50-year Lifespan Reveal Aging Trajectories and Signatures. Cell 2025. [Google Scholar] [CrossRef]
- Wei, Y.N.; Hu, H.Y.; Xie, G.C.; Fu, N.; Ning, Z.-B.; Zeng, R.; Khaitovich, P. Transcript and Protein Expression Decoupling Reveals RNA Binding Proteins and miRNAs as Potential Modulators of Human Aging. Genome Biol. 2015, 16, 41. [Google Scholar] [CrossRef] [PubMed]
- Böttger, E.C.; Santhosh Kumar, H.; Steiner, A.; Sotirakis, E.; Thiam, K.; Petit, P.I.; Seebeck, P.; Wolfer, D.P.; Scherbakov, D.; Akbergenov, R. Translational Error in Mice Increases with Ageing in an Organ-Dependent Manner. Nat. Commun. 2025, 16, 2069. [Google Scholar] [CrossRef]
- Zhu, D.; Arnold, M.; Samuelson, B.A.; Wu, J.Z.; Mueller, A.; Sinclair, D.A.; Kane, A.E. Sex Dimorphism and Tissue Specificity of Gene Expression Changes in Aging Mice. Biol. Sex Differ. 2024, 15, 89. [Google Scholar] [CrossRef] [PubMed]
- Schaum, N.; Lehallier, B.; Hahn, O.; Pálovics, R.; Hosseinzadeh, S.; Lee, S.E.; Sit, R.; Lee, D.P.; Losada, P.M.; Zardeneta, M.E.; et al. Ageing Hallmarks Exhibit Organ-Specific Temporal Signatures. Nature 2020, 583, 596–602. [Google Scholar] [CrossRef] [PubMed]
- Rao, S.; Le, A.Y.; Persyn, L.; Cenik, C. Translational Buffering Tunes Gene Expression in Mouse and Human. bioRxiv 2025. bioRxiv:2025.05.16.654561. [Google Scholar] [CrossRef]
- Kusnadi, E.P.; Timpone, C.; Topisirovic, I.; Larsson, O.; Furic, L. Regulation of gene expression via translational buffering. Biochim. Biophys. Acta Mol. Cell Res. 2022, 1869, 119140. [Google Scholar] [CrossRef]
- Khan, M.; Ullah, R.; Rehman, S.U.; Shah, S.A.; Saeed, K.; Muhammad, T.; Park, H.Y.; Jo, M.H.; Choe, K.; Rutten, B.P.F.; et al. 17β-Estradiol Modulates SIRT1 and Halts Oxidative Stress-Mediated Cognitive Impairment in a Male Aging Mouse Model. Cells 2019, 8, 928. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Klinge, C.M. Estrogenic control of mitochondrial function and biogenesis. J. Cell. Biochem. 2008, 105, 1342–1351. [Google Scholar] [CrossRef]
- Germain, D. Sirtuins and the Estrogen Receptor as Regulators of the Mammalian Mitochondrial UPR in Cancer and Aging. In Advances in Cancer Research; Tew, K.D., Fisher, P.B., Eds.; Academic Press: London, UK, 2016; Volume 130, pp. 211–256. [Google Scholar] [CrossRef]
- Moore, R.L.; Dai, Y.; Faller, D.V. Sirtuin 1 (SIRT1) and steroid hormone receptor activity in cancer. J. Endocrinol. 2012, 213, 37–48. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Dai, Y.; Ngo, D.; Forman, L.W.; Qin, D.C.; Jacob, J.; Faller, D.V. Sirtuin 1 is required for antagonist-induced transcriptional repression of androgen-responsive genes by the androgen receptor. Mol. Endocrinol. 2007, 21, 1807–1821. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Miao, J.; Huang, J.; Liang, Y.; Zhang, Y.; Li, J.; Meng, P.; Shen, W.; Li, X.; Wu, Q.; Wang, X.; et al. Sirtuin 6 is a key contributor to sex differences in acute kidney injury. Cell Death Discov. 2023, 9, 134. [Google Scholar] [CrossRef]
- Kananen, L.; Marttila, S. Ageing-Associated Changes in DNA Methylation in X and Y Chromosomes. Epigenetics Chromatin 2021, 14, 33. [Google Scholar] [CrossRef]
- Ma, W.; Fang, H.; Pease, N.; Filippova, G.N.; Disteche, C.M.; Berletch, J.B. Sex-Biased and Parental Allele-Specific Gene Regulation by KDM6A. Biol. Sex Differ. 2022, 13, 40. [Google Scholar] [CrossRef]
- Dimas, A.S.; Nica, A.C.; Montgomery, S.B.; Stranger, B.E.; Raj, T.; Buil, A.; Giger, T.; Lappalainen, T.; Gutierrez-Arcelus, M.; MuTHER Consortium; et al. Sex-Biased Genetic Effects on Gene Regulation in Humans. Genome Res. 2012, 22, 2368–2375. [Google Scholar] [CrossRef]
- Willcox, B.J.; Donlon, T.A.; He, Q.; Chen, R.; Grove, J.S.; Yano, K.; Masaki, K.H.; Willcox, D.C.; Rodriguez, B.; Curb, J.D. FOXO3A Genotype Is Strongly Associated with Human Longevity. Proc. Natl. Acad. Sci. USA 2008, 105, 13987–13992. [Google Scholar] [CrossRef] [PubMed]
- Brunet, A.; Sweeney, L.B.; Sturgill, J.F.; Chua, K.F.; Greer, P.L.; Lin, Y.; Tran, H.; Ross, S.E.; Mostoslavsky, R.; Cohen, H.Y.; et al. Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase. Science 2004, 303, 2011–2015. [Google Scholar] [CrossRef] [PubMed]
- Ji, J.S.; Liu, L.; Shu, C.; Yan, L.L.; Zeng, Y. Sex Difference and Interaction of SIRT1 and FOXO3 Candidate Longevity Genes on Life Expectancy: A 10-Year Prospective Longitudinal Cohort Study. J. Gerontol. A Biol. Sci. Med. Sci. 2022, 77, 1557–1563. [Google Scholar] [CrossRef] [PubMed]
- Anselmi, C.V.; Malovini, A.; Roncarati, R.; Novelli, V.; Villa, F.; Condorelli, G.; Puca, A.A. Association of the FOXO3A Locus with Extreme Longevity in a Southern Italian Centenarian Study. Rejuvenation Res. 2009, 12, 95–104. [Google Scholar] [CrossRef]
- Sampathkumar, N.K.; Bravo, J.I.; Chen, Y.; Danthi, P.S.; Donahue, E.K.; Lai, R.W.; Lu, R.; Randall, L.T.; Vinson, N.; Benayoun, B.A. Widespread sex dimorphism in aging and age-related diseases. Hum. Genet. 2020, 139, 333–356. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Keremidarska-Markova, M.; Sazdova, I.; Mladenov, M.; Pilicheva, B.; Zagorchev, P.; Gagov, H. Sirtuin 1 and Hormonal Regulations in Aging. Appl. Sci. 2024, 14, 12051. [Google Scholar] [CrossRef]
- Barcena de Arellano, M.L.; Pozdniakova, S.; Kühl, A.A.; Baczko, I.; Ladilov, Y.; Regitz-Zagrosek, V. Sex differences in the aging human heart: Decreased sirtuins, pro-inflammatory shift and reduced anti-oxidative defense. Aging 2019, 11, 1918–1933. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Breitenstein, A.; Wyss, C.A.; Spescha, R.D.; Franzeck, F.C.; Hof, D.; Riwanto, M.; Hasun, M.; Akhmedov, A.; von Eckardstein, A.; Maier, W.; et al. Peripheral Blood Monocyte Sirt1 Expression Is Reduced in Patients with Coronary Artery Disease. PLoS ONE 2013, 8, e53106. [Google Scholar] [CrossRef] [PubMed]
- Kong, B.; Zheng, X.; Hu, Y.; Zhao, Y.; Hai, J.; Ti, Y.; Bu, P. Sirtuin3 attenuates pressure overload-induced pathological myocardial remodeling by inhibiting cardiomyocyte cuproptosis. Pharmacol. Res. 2025, 216, 107739. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.P.; Wen, R.; Liu, C.F.; Zhang, T.N.; Yang, N. Cellular and molecular biology of sirtuins in cardiovascular disease. Biomed. Pharmacother. 2023, 164, 114931. [Google Scholar] [CrossRef] [PubMed]
- Kanfi, Y.; Naiman, S.; Amir, G.; Peshti, V.; Zinman, G.; Nahum, L.; Bar-Joseph, Z.; Cohen, H.Y. The sirtuin SIRT6 regulates lifespan in male mice. Nature 2012, 483, 218–221. [Google Scholar] [CrossRef] [PubMed]
- Rose, G.; Dato, S.; Altomare, K.; Bellizzi, D.; Garasto, S.; Greco, V.; Passarino, G.; Feraco, E.; Mari, V.; Barbi, C.; et al. Variability of the SIRT3 gene, human silent information regulator Sir2 homologue, and survivorship in the elderly. Exp. Gerontol. 2003, 38, 1065–1070. [Google Scholar] [CrossRef] [PubMed]
Marker | YA | MA | VO |
---|---|---|---|
Protein levels (S-) | |||
S-SIRT1 | 2.23 [2.21; 2.31] | 1.41 [0.80; 2.02] | 0.98 [0.41; 1.58] |
S-SIRT3 | 2.90 [2.88; 2.97] | 1.79 [1.34; 2.11] | 1.24 [0.54; 2.00] |
S-SIRT6 | 3.70 [3.65; 3.75] | 2.52 [2.00; 2.69] | 1.34 [0.61; 2.11] |
mRNA levels | |||
mRNA–SIRT1 | 1.21 [1.13; 1.26] | 0.93 [0.88; 1.07] | 0.70 [0.51; 0.83] |
mRNA–SIRT3 | 1.59 [1.57; 1.60] | 0.90 [0.78; 1.35] | 0.72 [0.59; 0.81] |
mRNA–SIRT6 | 2.07 [2.04; 2.09] | 0.99 [0.92; 1.07] | 0.63 [0.30; 0.96] |
Protein-to-mRNA ratio (PTR) | |||
SIRT1/mRNA | 1.98 [1.84; 2.09] | 1.36 [0.91; 1.73] | 1.33 [0.81; 1.90] |
SIRT3/mRNA | 1.85 [1.83; 1.88] | 1.79 [1.06; 2.18] | 1.70 [0.90; 2.47] |
SIRT6/mRNA | 1.76 [1.76; 1.80] | 2.57 [2.36; 2.64] | 2.08 [1.94; 2.22] |
Marker | MA vs. YA (%) | VO vs. MA (%) | VO Remaining vs. YA (%) |
---|---|---|---|
Protein levels (S-) | |||
S-SIRT1 | −36.8 | −30.5 | 43.9% |
S-SIRT3 | −38.3 | −30.8 | 42.8% |
S-SIRT6 | −31.9 | −46.8 | 36.2% |
mRNA levels | |||
mRNA–SIRT1 | −23.2 | −24.7 | 57.9% |
mRNA–SIRT3 | −43.4 | −20.0 | 45.3% |
mRNA–SIRT6 | −51.2 | −36.4 | 30.4% |
Protein-to-mRNA ratio (PTR) | |||
SIRT1/mRNA | −31.3 | −2.2 | 67.2% |
SIRT3/mRNA | −3.2 | −5.0 | 91.9% |
SIRT6/mRNA | +46.0 | −19.1 | 118.2% |
Marker | YA (♂ + ♀) | MA ♂ | MA ♀ | VO ♂ | VO ♀ |
---|---|---|---|---|---|
Protein levels (S-) | |||||
S-SIRT1 | 2.23 [2.21; 2.31] | 0.81 [0.77; 2.02] | 1.99 [0.83; 2.10] | 0.41 [0.41; 0.45] | 1.60 [1.52; 1.67] |
S-SIRT3 | 2.90 [2.88; 2.97] | 1.34 [1.34; 2.04] | 2.00 [1.57; 2.13] | 0.58 [0.50; 0.60] | 2.01 [1.67; 2.10] |
S-SIRT6 | 3.70 [3.65; 3.75] | 2.55 [2.34; 2.69] | 2.50 [1.89; 2.67] | 0.65 [0.59; 0.67] | 2.11 [2.10; 2.14] |
mRNA levels | |||||
mRNA–SIRT1 | 1.21 [1.13; 1.26] | 0.97 [0.90; 1.10] | 0.91 [0.87; 0.94] | 0.51 [0.49; 0.59] | 0.83 [0.80; 0.83] |
mRNA–SIRT3 | 1.59 [1.57; 1.60] | 1.22 [0.88; 1.40] | 0.83 [0.75; 0.92] | 0.60 [0.56; 0.65] | 0.82 [0.79; 0.83] |
mRNA–SIRT6 | 2.07 [2.04; 2.09] | 0.99 [0.99; 1.00] | 1.01 [0.80; 1.07] | 0.33 [0.29; 0.34] | 0.96 [0.92; 0.96] |
Protein-to-mRNA ratio (PTR) | |||||
SIRT1/mRNA | 1.88 [1.81; 1.98] | 0.99 [0.90; 1.81] | 1.73 [0.95; 2.23] | 0.82 [0.80; 0.92] | 1.90 [1.88; 2.01] |
SIRT3/mRNA | 1.87 [1.85; 1.88] | 1.10 [0.96; 1.81] | 2.09 [1.76; 2.17] | 0.92 [0.85; 1.04] | 2.45 [2.37; 2.47] |
SIRT6/mRNA | 1.78 [1.77; 1.80] | 2.58 [2.56; 2.69] | 2.43 [2.36; 2.64] | 2.03 [1.91; 2.03] | 2.20 [2.16; 2.23] |
Marker | Δ MA vs. YA % in ♂ | Δ VO vs. MA % in ♂ | Δ MA vs. YA % in ♀ | ΔVO vs. MA % in ♀ |
---|---|---|---|---|
Protein levels (S-) | ||||
sSIRT1 | −63.7 | −49.4 | −10.7 | −19.6 |
sSIRT3 | −53.8 | −56.7 | −31.0 | +0.5 |
sSIRT6 | −31.1 | −74.5 | −32.4 | −15.6 |
mRNA levels | ||||
mRNA-SIRT1 | −19.8 | −48.5 | −24.8 | −8.8 |
mRNA-SIRT3 | −23.3 | −50.8 | −47.8 | −1.2 |
mRNA-SIRT6 | −52.2 | −66.7 | −51.2 | −5.0 |
Protein-to-mRNA ratio (PTR) | ||||
SIRT1/mRNA | −47.3 | −8.9 | −7.9 | +9.8 |
SIRT3/mRNA | −41.2 | −16.4 | +11.8 | +13.4 |
SIRT6/mRNA | +44.9 | −21.3 | +36.0 | −9.5 |
Marker | CVD (–) Median [Q1; Q3] | CVD (+) Median [Q1; Q3] | Δ CVD (+) vs. CVD (−) (%) | p (M-W) | Effect Size r |
---|---|---|---|---|---|
Protein levels (S-) | |||||
S-SIRT1 | 2.01 [1.67; 2.12] | 0.44 [0.41; 0.78] | 78% | 6.3 × 10−5 | 0.84 |
S-SIRT3 | 2.12 [2.01; 2.86] | 0.62 [0.54; 1.18] | 71% | 6.3 × 10−5 | 0.84 |
S-SIRT6 | 2.55 [2.14; 3.49] | 0.70 [0.60; 1.65] | 73% | 1.7 × 10−3 | 0.69 |
mRNA levels | |||||
mRNA–SIRT1 | 0.94 [0.85; 1.12] | 0.55 [0.49; 0.84] | 42% | 2.9 × 10−3 | 0.63 |
mRNA–SIRT3 | 0.88 [0.83; 1.59] | 0.64 [0.59; 0.76] | 27% | 2.6 × 10−3 | 0.63 |
mRNA–SIRT6 | 1.01 [0.96; 1.12] | 0.34 [0.29; 0.85] | 66% | 1.0 × 10−3 | 0.69 |
Protein-to-mRNA ratio (PTR) | |||||
SIRT1/mRNA | 1.90 [1.81; 2.09] | 0.86 [0.81; 0.91] | 55% | 6.3 × 10−5 | 0.84 |
SIRT3/mRNA | 2.32 [1.85; 2.47] | 0.95 [0.90; 1.05] | 59% | 2.2 × 10−4 | 0.77 |
SIRT6/mRNA | 2.23 [2.12; 2.56] | 2.03 [1.87; 2.42] | 9% | 5.6 × 10−1 | 0.11 |
Marker | VO vs. YA, CVD-Free (%) | VO vs. YA, All 23 (%) | p (CVD-Free) |
---|---|---|---|
Protein levels (S-) | |||
S-SIRT1 | 71.7 | 43.9 | 0.036 |
S-SIRT3 | 69.3 | 42.8 | 0.036 |
S-SIRT6 | 57.0 | 36.2 | 0.036 |
mRNA levels | |||
mRNA–SIRT1 | 68.6 | 57.9 | 0.036 |
mRNA–SIRT3 | 51.6 | 45.3 | 0.036 |
mRNA–SIRT6 | 46.4 | 30.4 | 0.036 |
Protein-to-mRNA ratio (PTR) | |||
SIRT1/mRNA | 95.8 | 67.2 | 0.053 |
SIRT3/mRNA | 133.6 | 91.9 | 0.036 |
SIRT6/mRNA | 124.5 | 118.2 | 0.036 |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Hashimova, U.; Kvetnoy, I.; Gaisina, A.; Safikhanova, K.; Mironova, E.; Galandarli, I.; Hasanli, L. SIRT1/3/6 Landscape of Human Longevity: A Sex- and Health-Stratified Pilot Study. Biology 2025, 14, 1353. https://doi.org/10.3390/biology14101353
Hashimova U, Kvetnoy I, Gaisina A, Safikhanova K, Mironova E, Galandarli I, Hasanli L. SIRT1/3/6 Landscape of Human Longevity: A Sex- and Health-Stratified Pilot Study. Biology. 2025; 14(10):1353. https://doi.org/10.3390/biology14101353
Chicago/Turabian StyleHashimova, Ulduz, Igor Kvetnoy, Aliya Gaisina, Khatira Safikhanova, Ekaterina Mironova, Irana Galandarli, and Lala Hasanli. 2025. "SIRT1/3/6 Landscape of Human Longevity: A Sex- and Health-Stratified Pilot Study" Biology 14, no. 10: 1353. https://doi.org/10.3390/biology14101353
APA StyleHashimova, U., Kvetnoy, I., Gaisina, A., Safikhanova, K., Mironova, E., Galandarli, I., & Hasanli, L. (2025). SIRT1/3/6 Landscape of Human Longevity: A Sex- and Health-Stratified Pilot Study. Biology, 14(10), 1353. https://doi.org/10.3390/biology14101353