D. W. Walker et al., "Evolution of Lifespan in C. elegans," Nature 405, no. 6784 (May 18, 2000): 296–97, https://doi.org/10.1038/35012693.

253

Stephen O'Rahilly, разговор с автором 11 августа 2022 г.

254

H. R. Bridges et al., "Structural Basis of Mammalian Respiratory Complex I Inhibition by Medicinal Biguanides," Science 379, no. 6630 (January 26, 2023): 351–57, https://www.science.org/doi/10.1126/science.ade3332.

255

G. Rena, D. G. Hardie, and E. R. Pearson, "The Mechanisms of Action of Metformin," Diabetologia 60, no. 9 (September 2017): 1577–85, https://doi.org/10.1007/s00125–017–4342-z; T. E. LaMoia and G. I. Shulman, "Cellular and Molecular Mechanisms of Metformin Action," Endocrine Reviews 42, no. 1 (February 2021): 77–96, https://doi.org/10.1210/endrev/bnaa023.

256

L. C. Gormsen et al., "Metformin Increases Endogenous Glucose Production in Non-Diabetic Individuals and Individuals with Recent-Onset Type 2 Diabetes," Diabetologia 62, no. 7 (July 2019): 1251–56, https://doi.org/10.1007/s00125–019–4872–7.

257

H. Wu et al., "Metformin Alters the Gut Microbiome of Individuals with TreatmentNaive Type 2 Diabetes, Contributing to the Therapeutic Effects of the Drug," Nature Medicine 23, no. 7 (July 2017): 850–58, https://doi.org/10.1038/nm.4345.

258

A. P. Coll et al., "GDF15 Mediates the Effects of Metformin on Body Weight and Energy Balance," Nature 578, no. 7795 (February 2020): 444–48, https://doi.org/10.1038/s41586–019–1911-y.

259

A. Martin-Montalvo et al., "Metformin Improves Healthspan and Lifespan in Mice," Nature Communications 4 (2013): 2192, https://doi.org/10.1038/ncomms3192.

260

C. A. Bannister et al., "Can People with Type 2 Diabetes Live Longer Than Those Without? A Comparison of Mortality in People Initiated with Metformin or Sulphonylurea Monotherapy and Matched, Non-Diabetic Controls," Diabetes, Obesity and Metabolism 16, no. 11 (November 2014): 1165–73, https://doi.org/10.1111/dom.12354.

261

M. Claesen et al., "Mortality in Individuals Treated with Glucose-Lowering Agents: A Large, Controlled Cohort Study," Journal of Clinical Endocrinology & Metabolism 101, no. 2 (February 1, 2016): 461–69, https://doi.org/10.1210/jc.2015–3184.

262

L. Espada et al., "Loss of Metabolic Plasticity Underlies Metformin Toxicity in Aged Caenorhabditis Elegans," Nature Metabolism 2, no. 11 (November 2020): 1316–31, https://doi.org/10.1038/s42255–020–00307–1.

263

A. R. Konopka et al., "Metformin Inhibits Mitochondrial Adaptations to Aerobic Exercise Training in Older Adults," Aging Cell 18, no. 1 (February 2019): e12880, https://doi.org/10.1111/acel.12880.

264

Y. C. Kuan et al., "Effects of Metformin Exposure on Neurodegenerative Diseases in Elderly Patients with Type 2 Diabetes Mellitus," Progress in Neuropsychopharmacol and Biological Psychiatry 79, pt. B (October 3, 2017): 1777–83(2017), https://doi.org/10.1016/j.pnpbp.2017.06.002.

265

"The Tame Trial: Targeting the Biology of Aging: Ushering a New Era of Interventions," American Federation for Aging Research (AFAR) online, дата обращения 01.08.2023, https://www.afar.org/tame-trial.

266

Подробный рассказ о том, как Гваренте начал изучать этот предмет и о первых открытиях, сделанных его лабораторией, содержится в книге: Lenny Guarente, Ageless Quest: One Scientist's Search for Genes That Prolong Youth (Cold Spring Harbor, NY: Cold Spring Harbor Press, 2003).

267

M. Kaeberlein, M. McVey, and L. Guarente, "The SIR2/3/4 Complex and SIR2 Alone Promote Longevity in Saccharomyces cerevisiae by Two Different Mechanisms," Genes and Development 13, no. 19, October 1, 1994, 2570–80, https://doi.org/10.1101/gad.13.19.2570.

268

B. Rogina and S. L. Helfand, "Sir2 Mediates Longevity in the Fly Through a Pathway Related to Calorie Restriction," Proceedings of the National Academy of Sciences (PNAS) of the United States of America 101, no. 45 (November 2004): 15998–6003, https://doi.org/10.1073 /Pnas.040418410; H. A. Tissenbaum and L. Guarente, "Increased Dosage of a Sir–2 Gene Extends Lifespan in Caenorhabditis Elegans," Nature 410, no. 6825 (March 8, 2001): 227–30, https://doi.org/10.1038/35065638.

269

S. Imai et al., "Transcriptional Silencing and Longevity Protein Sir2 Is an NAD-Dependent Histone Deacetylase," Nature 403, no. 6771 (February 17, 2000): 795–800, https://doi.org/10.1038/35001622; W. Dang et al., "Histone H4 Lysine 16 Acetylation Regulates Cellular Lifespan," Nature 459, no. 7248 (June 11, 2009): 802–7, https://doi.org/10.1038/nature08085.

270

S. J. Lin, P. A. Defossez, and L. Guarente, "Requirement of NAD and SIR2 for Life-span Extension by Calorie Restriction in Saccharomyces cerevisiae," Science 289, no. 5487 (September 22, 2000): 2126–28, https://doi.org/10.1126/science.289.5487.2126; Rogina and Helfand, "Sir2 Mediates Longevity in the Fly," 15998–6003.

271

L. Guarente and C. Kenyon, "Genetic Pathways That Regulate Ageing in Model Organisms," Nature 408, no. 6809 (November 9, 2000): 255–62, https://doi.org/10.1038/35041700.

272

K. T. Howitz. et al., "Small Molecule Activators of Sirtuins Extend Saccharomyces cerevisiae Lifespan," Nature 425, no. 6809 (November 9, 2000): 191–96, https://doi.org/10.1038/nature01960.

273

J. A. Baur et al., "Resveratrol Improves Health and Survival of Mice on a High-Calorie Diet," Nature 444, no. 7117 (November 16, 2006): 337–42, https://doi.org/10.1038/nature05354; M. Lagouge et al., "Resveratrol Improves Mitochondrial Function and Protects Against Metabolic Disease by Activating SIRT1 and PGC–1alpha," Cell 127, no. 6 (December 15, 2006): 1109–22, https://doi.org/10.1016/j.cell.2006.11.013.

274

M. Kaeberlein et al., "Sir2–Independent Life Span Extension by Calorie Restriction in Yeast," PLoS Biology 2, no. 9 (September 2004): E296, https://doi.org/10.1371/journal.pbio.0020296.

275

M. Kaeberlein et al., "Substrate-Specific Activation of Sirtuins by Resveratrol," Journal of Biological Chemistry 280, no. 17 (April 2005): 17038–45, https://doi.org/10.1074/jbc.M500655200.

276

M. Pacholec et al., "SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1," Journal of Biological Chemistry 285, no. 11 (March 2010): 8340–51, https://doi.org/10.1074/jbc.M109.088682.

277

John La Mattina, "Getting the Benefits of Red Wine from a Pill? Not Likely," Forbes online, дата последнего изменения 19.03.2013, https://www.forbes.com/sites/johnlamattina/2013/03/19/getting-the-benefits-of-red-wine-from-a-pill-not-likely/.

278

B. P. Hubbard et al., "Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators," Science 339, no. 6124 (March 8, 2013): 1216–19, https://doi.org/10.1126/science.1231097; H. Yuan and R. Marmorstein, "Red Wine, Toast of the Town (Again)," Science 339, no. 6124 (March 8, 2013): 1156–57, https://doi.org/10.1126/science.1236463.

279

R. Strong et al., "Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice," Journals of Gerontology: Series A 68, no. 1 (January 2013): 6–16, https://doi.org/10.1093/gerona/gls070.

280

P. Fabrizio et al., "Sir2 Blocks Extreme Life-span Extension," Cell 123, no. 4 (November 18, 2005): 655–67, https://doi.org/10.1016/j.cell.2005.08.042; см. также комментарии Б. Кеннеди, Э. Смита и М. Кэберлейна: B. K. Kennedy, E. D. Smith, and M. Kaeberlein, "The Enigmatic Role of Sir2 in Aging," Cell 123, no. 4 (November 18, 2005): 548–50, https://doi.org/10.1016/j.cell.2005.11.002.

281

C. Burnett et al., "Absence of Effects of Sir2