Targeting aging mechanisms: pharmacological perspectives

Moskalev, 2020, Is anti-ageing drug discovery becoming a reality?, Expert Opin. Drug Discov., 15, 135, 10.1080/17460441.2020.1702965 Gómez-Linton, 2019, Some naturally occurring compounds that increase longevity and stress resistance in model organisms of aging, Biogerontology, 20, 583, 10.1007/s10522-019-09817-2 Partridge, 2020, The quest to slow ageing through drug discovery, Nat. Rev. Drug Discov., 19, 513, 10.1038/s41573-020-0067-7 Moskalev, 2015, Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease, Aging (Albany NY), 7, 616, 10.18632/aging.100799 Barardo, 2017, The DrugAge database of aging-related drugs, Aging Cell, 16, 594, 10.1111/acel.12585 Khaltourina, 2020, Aging fits the disease criteria of the International Classification of Diseases, Mech. Ageing Dev., 189, 10.1016/j.mad.2020.111230 Kaeberlein, 2018, How healthy is the healthspan concept?, GeroScience, 40, 361, 10.1007/s11357-018-0036-9 Moskalev, 2017, Geroprotectors: a unified concept and screening approaches, Aging Dis., 8, 354, 10.14336/AD.2016.1022 Moskalev, 2016, Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic, Aging Cell, 15, 407, 10.1111/acel.12463 Liguori, 2018, Oxidative stress, aging, and diseases, Clin. Interv. Aging, 13, 757, 10.2147/CIA.S158513 Aune, 2018, Dietary intake and blood concentrations of antioxidants and the risk of cardiovascular disease, total cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective studies, Am. J. Clin. Nutr., 108, 1069, 10.1093/ajcn/nqy097 Khan, 2019, Effects of nutritional supplements and dietary interventions on cardiovascular outcomes: an umbrella review and evidence map, Ann. Intern. Med., 171, 190, 10.7326/M19-0341 Guvatova, 2020, Protective effects of carotenoid fucoxanthin in fibroblasts cellular senescence, Mech. Ageing Dev., 189, 10.1016/j.mad.2020.111260 Milisav, 2018, Antioxidant vitamins and ageing, Subcell. Biochem., 90, 1, 10.1007/978-981-13-2835-0_1 Forman, 2021, Targeting oxidative stress in disease: promise and limitations of antioxidant therapy, Nat. Rev. Drug Discov., 20, 689, 10.1038/s41573-021-00233-1 Zimniak, 2011, Relationship of electrophilic stress to aging, Free Radic. Biol. Med., 51, 1087, 10.1016/j.freeradbiomed.2011.05.039 Rikans, 1997, Lipid peroxidation, antioxidant protection and aging, Biochim. Biophys. Acta Mol. Basis Dis., 1362, 116, 10.1016/S0925-4439(97)00067-7 Hatami, 2018, Deuterium-reinforced linoleic acid lowers lipid peroxidation and mitigates cognitive impairment in the Q140 knock in mouse model of Huntington’s disease, FEBS J., 285, 3002, 10.1111/febs.14590 Zesiewicz, 2018, Randomized, clinical trial of RT001: early signals of efficacy in Friedreich’s ataxia, Mov. Disord., 33, 1000, 10.1002/mds.27353 Koh, 2019, Lysosomal dysfunction in proteinopathic neurodegenerative disorders: possible therapeutic roles of cAMP and zinc, Mol. Brain, 12, 18, 10.1186/s13041-019-0439-2 Madeo, 2019, Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?, Autophagy, 15, 165, 10.1080/15548627.2018.1530929 Galluzzi, 2017, Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles, Nat. Rev. Drug Discov., 16, 487, 10.1038/nrd.2017.22 Bhukel, 2017, Spermidine boosts autophagy to protect from synapse aging, Autophagy, 13, 444, 10.1080/15548627.2016.1265193 Carmona-Gutierrez, 2016, The crucial impact of lysosomes in aging and longevity, Ageing Res. Rev., 32, 2, 10.1016/j.arr.2016.04.009 Saez, 2014, The mechanistic links between proteasome activity, aging and age-related diseases, Curr. Genomics, 15, 38, 10.2174/138920291501140306113344 Leestemaker, 2017, Proteasome activation by small molecules, Cell Chem. Biol., 24, 725, 10.1016/j.chembiol.2017.05.010 Trader, 2017, Establishment of a suite of assays that support the discovery of proteasome stimulators, Biochim. Biophys. Acta Gen. Subj., 1861, 892, 10.1016/j.bbagen.2017.01.003 Pallauf, 2017, A literature review of flavonoids and lifespan in model organisms, Proc. Nutr. Soc., 76, 145, 10.1017/S0029665116000720 Yessenkyzy, 2020, Polyphenols as caloric-restriction mimetics and autophagy inducers in aging research, Nutrients, 12, 1344, 10.3390/nu12051344 Mira, 2002, Interactions of flavonoids with iron and copper ions: a mechanism for their antioxidant activity, Free Radic. Res., 36, 1199, 10.1080/1071576021000016463 Biradar, 2019, Chebulinic acid and Boeravinone B act as anti-aging and anti-apoptosis phyto-molecules during oxidative stress, Mitochondrion, 46, 236, 10.1016/j.mito.2018.07.003 Shen, 2017, Piceatannol extends the lifespan of Caenorhabditis elegans via DAF-16, Biofactors, 43, 379, 10.1002/biof.1346 Ou, 2017, Effect of rosmarinic acid and carnosic acid on AGEs formation in vitro, Food Chem., 221, 1057, 10.1016/j.foodchem.2016.11.056 Nagai, 2012, Chelation: a fundamental mechanism of action of AGE inhibitors, AGE breakers, and other inhibitors of diabetes complications, Diabetes, 61, 549, 10.2337/db11-1120 Panigrahi, 1996, α-Lipoic acid protects against reperfusion injury following cerebral ischemia in rats, Brain Res., 717, 184, 10.1016/0006-8993(96)00009-1 Li, 2014, α-Lipoic acid prolongs survival and attenuates acute kidney injury in a rat model of sepsis, Clin. Exp. Pharmacol. Physiol., 41, 459, 10.1111/1440-1681.12244 Vannuruswamy, 2016, Molecules with O-acetyl group protect protein glycation by acetylating lysine residues, RSC Adv., 6, 65572, 10.1039/C6RA11313C Jud, 2019, Therapeutic options to reduce advanced glycation end products in patients with diabetes mellitus: a review, Diabetes Res. Clin. Pract., 148, 54, 10.1016/j.diabres.2018.11.016 Panwar, 2018, Aging-associated modifications of collagen affect its degradation by matrix metalloproteinases, Matrix Biol., 65, 30, 10.1016/j.matbio.2017.06.004 Ewald, 2015, Dauer-independent insulin/IGF-1-signalling implicates collagen remodelling in longevity, Nature, 519, 97, 10.1038/nature14021 Fhayli, 2019, Chronic administration of minoxidil protects elastic fibers and stimulates their neosynthesis with improvement of the aorta mechanics in mice, Cell. Signal., 62, 10.1016/j.cellsig.2019.05.018 Gorbunova, 2021, The role of retrotransposable elements in ageing and age-associated diseases, Nature, 596, 43, 10.1038/s41586-021-03542-y De Cecco, 2013, Genomes of replicatively senescent cells undergo global epigenetic changes leading to gene silencing and activation of transposable elements, Aging Cell, 12, 247, 10.1111/acel.12047 De Cecco, 2019, L1 drives IFN in senescent cells and promotes age-associated inflammation, Nature, 566, 73, 10.1038/s41586-018-0784-9 Simon, 2019, LINE1 derepression in aged wild-type and SIRT6-deficient mice drives inflammation, Cell Metab., 29, 871, 10.1016/j.cmet.2019.02.014 Shay, 2019, Telomeres and telomerase: three decades of progress, Nat. Rev. Genet., 20, 299, 10.1038/s41576-019-0099-1 Amano, 2019, Telomere dysfunction induces sirtuin repression that drives telomere-dependent disease, Cell Metab., 29, 1274, 10.1016/j.cmet.2019.03.001 Moskalev, 2014, Genetics and epigenetics of aging and longevity, Cell Cycle, 13, 1063, 10.4161/cc.28433 Dai, 2018, Sirtuin activators and inhibitors: promises, achievements, and challenges, Pharmacol. Ther., 188, 140, 10.1016/j.pharmthera.2018.03.004 McIntyre, 2019, From molecular promise to preclinical results: HDAC inhibitors in the race for healthy aging drugs, EMBO Mol. Med., 11, 10.15252/emmm.201809854 Fahy, 2019, Reversal of epigenetic aging and immunosenescent trends in humans, Aging Cell, 18, 10.1111/acel.13028 Gensous, 2020, One-year Mediterranean diet promotes epigenetic rejuvenation with country- and sex-specific effects: a pilot study from the NU-AGE project, Geroscience, 42, 687, 10.1007/s11357-019-00149-0 Palmeira, 2019, Mitohormesis and metabolic health: the interplay between ROS, cAMP and sirtuins, Free Radic. Biol. Med., 141, 483, 10.1016/j.freeradbiomed.2019.07.017 Cameron, 2018, Metformin selectively targets redox control of complex I energy transduction, Redox Biol., 14, 187, 10.1016/j.redox.2017.08.018 De Haes, 2014, Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2, Proc. Natl. Acad. Sci. U. S. A., 111, E2501, 10.1073/pnas.1321776111 Abdelgadir, 2017, Effect of metformin on different non-diabetes related conditions, a special focus on malignant conditions: review of literature, J. Clin. Med. Res., 9, 388, 10.14740/jocmr2922e Desilets, 2008, Role of metformin for weight management in patients without type 2 diabetes, Ann. Pharmacother., 42, 817, 10.1345/aph.1K656 Ustinova, 2019, Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals, PLoS One, 14, 10.1371/journal.pone.0224835 Lv, 2020, Metformin and its benefits for various diseases, Front. Endocrinol., 11, 191, 10.3389/fendo.2020.00191 Lally, 2021, Metformin is associated with decreased 30-day mortality among nursing home residents infected with SARS-CoV2, J. Am. Med. Dir. Assoc., 22, 193, 10.1016/j.jamda.2020.10.031 Justice, 2018, A framework for selection of blood-based biomarkers for geroscience-guided clinical trials: report from the TAME Biomarkers Workgroup, Geroscience, 40, 419, 10.1007/s11357-018-0042-y Konopka, 2019, Taming expectations of metformin as a treatment to extend healthspan, Geroscience, 41, 101, 10.1007/s11357-019-00057-3 Quach, 2017, Epigenetic clock analysis of diet, exercise, education, and lifestyle factors, Aging (Albany NY), 9, 419, 10.18632/aging.101168 Konopka, 2019, Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults, Aging Cell, 18, 10.1111/acel.12880 Sharoff, 2010, Combining short-term metformin treatment and one bout of exercise does not increase insulin action in insulin-resistant individuals, Am. J. Physiol. Endocrinol. Metab., 298, E815, 10.1152/ajpendo.00517.2009 Zhu, 2020, The mitohormetic response as part of the cytoprotection mechanism of berberine: berberine induces mitohormesis and mechanisms, Mol. Med., 26, 10, 10.1186/s10020-020-0136-8 Miller, 2018, Nutritional ketosis and mitohormesis: potential implications for mitochondrial function and human health, J. Nutr. Metab., 2018, 10.1155/2018/5157645 Fang, 2019, Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease, Nat. Neurosci., 22, 401, 10.1038/s41593-018-0332-9 Toney, 2019, Urolithin A, a gut metabolite, improves insulin sensitivity through augmentation of mitochondrial function and biogenesis, Obesity (Silver Spring), 27, 612, 10.1002/oby.22404 Ryu, 2016, Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents, Nat. Med., 22, 879, 10.1038/nm.4132 Andreux, 2019, The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans, Nat. Metab., 1, 595, 10.1038/s42255-019-0073-4 Demarest, 2019, NAD+ metabolism in aging and cancer, Annu. Rev. Cancer Biol., 3, 105, 10.1146/annurev-cancerbio-030518-055905 Kellenberger, 2011, Flavonoids as inhibitors of human CD38, Bioorg. Med. Chem. Lett., 21, 3939, 10.1016/j.bmcl.2011.05.022 Lashmanova, 2017, The evaluation of geroprotective effects of selected flavonoids in Drosophila melanogaster and Caenorhabditis elegans, Front. Pharmacol., 8, 884, 10.3389/fphar.2017.00884 Conze, 2019, Safety and metabolism of long-term administration of NIAGEN (nicotinamide riboside chloride) in a randomized, double-blind, placebo-controlled clinical trial of healthy overweight adults, Sci. Rep., 9, 9772, 10.1038/s41598-019-46120-z Poddar, 2019, Nicotinamide mononucleotide: exploration of diverse therapeutic applications of a potential molecule, Biomolecules, 9, 34, 10.3390/biom9010034 Tarantini, 2019, Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice, Redox Biol., 24, 10.1016/j.redox.2019.101192 Rabanal-Ruiz, 2017, mTORC1 as the main gateway to autophagy, Essays Biochem., 61, 565, 10.1042/EBC20170027 Ahmed, 2019, Hyperactive TORC1 sensitizes yeast cells to endoplasmic reticulum stress by compromising cell wall integrity, FEBS Lett., 593, 1957, 10.1002/1873-3468.13463 Bitto, 2016, Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice, eLife, 5, 10.7554/eLife.16351 Baselga, 2009, Phase II randomized study of neoadjuvant everolimus plus letrozole compared with placebo plus letrozole in patients with estrogen receptor-positive breast cancer, J. Clin. Oncol., 27, 2630, 10.1200/JCO.2008.18.8391 Guarda, 2004, Oral rapamycin to prevent human coronary stent restenosis: a pilot study, Am. Heart J., 148, 341, 10.1016/j.ahj.2004.03.046 Mannick, 2014, mTOR inhibition improves immune function in the elderly, Sci. Transl. Med., 6, 10.1126/scitranslmed.3009892 Salmon, 2015, About-face on the metabolic side effects of rapamycin, Oncotarget, 6, 2585, 10.18632/oncotarget.3354 Deblon, 2012, Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats, Br. J. Pharmacol., 165, 2325, 10.1111/j.1476-5381.2011.01716.x Kim, 2020, Rapamycin increases the incidence of neuropsychiatric illness in kidney transplant patients through the suppression of neural stem cells, Transl. Psychiatry, 10, 156, 10.1038/s41398-020-0838-2 Mannick, 2018, TORC1 inhibition enhances immune function and reduces infections in the elderly, Sci. Transl. Med., 10, 10.1126/scitranslmed.aaq1564 Longo, 2003, The Ras and Sch9 pathways regulate stress resistance and longevity, Exp. Gerontol., 38, 807, 10.1016/S0531-5565(03)00113-X Slack, 2015, The Ras–Erk–ETS signaling pathway is a drug target for longevity, Cell, 162, 72, 10.1016/j.cell.2015.06.023 Danilov, 2013, Selective anticancer agents suppress aging in Drosophila, Oncotarget, 4, 1507, 10.18632/oncotarget.1272 Admasu, 2018, Drug synergy slows aging and improves healthspan through IGF and SREBP lipid signaling, Dev. Cell, 47, 67, 10.1016/j.devcel.2018.09.001 Mehdipour, 2019, Rejuvenation of brain, liver and muscle by simultaneous pharmacological modulation of two signaling determinants, that change in opposite directions with age, Aging (Albany NY), 11, 5628, 10.18632/aging.102148 Castillo-Quan, 2019, A triple drug combination targeting components of the nutrient-sensing network maximizes longevity, Proc. Natl. Acad. Sci. U. S. A., 116, 20817, 10.1073/pnas.1913212116 Castillo-Quan, 2016, Lithium promotes longevity through GSK3/NRF2-dependent hormesis, Cell Rep., 15, 638, 10.1016/j.celrep.2016.03.041 Til, 1997, Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats, Food Chem. Toxicol., 35, 337, 10.1016/S0278-6915(97)00121-X Singh, 2018, Toxicological effects of berberine and sanguinarine, Front. Mol. Biosci., 5, 21, 10.3389/fmolb.2018.00021 Qi, 2021, Sulforaphane promotes C. elegans longevity and healthspan via DAF-16/DAF-2 insulin/IGF-1 signaling, Aging (Albany NY), 13, 1649, 10.18632/aging.202512 Zhu, 2015, The Achilles' heel of senescent cells: from transcriptome to senolytic drugs, Aging Cell, 14, 644, 10.1111/acel.12344 Hickson, 2019, Senolytics decrease senescent cells in humans: preliminary report from a clinical trial of dasatinib plus quercetin in individuals with diabetic kidney disease, eBioMedicine, 47, 446, 10.1016/j.ebiom.2019.08.069 Schafer, 2017, Cellular senescence mediates fibrotic pulmonary disease, Nat. Commun., 8, 14532, 10.1038/ncomms14532 Justice, 2019, Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study, eBioMedicine, 40, 554, 10.1016/j.ebiom.2018.12.052 Kang, 2019, Senolytics and senostatics: a two-pronged approach to target cellular senescence for delaying aging and age-related diseases, Mol. Cells, 42, 821 Lewinska, 2020, AMPK-mediated senolytic and senostatic activity of quercetin surface functionalized Fe3O4 nanoparticles during oxidant-induced senescence in human fibroblasts, Redox Biol., 28, 10.1016/j.redox.2019.101337 da Silva, 2019, The bystander effect contributes to the accumulation of senescent cells in vivo, Aging Cell, 18, 10.1111/acel.12848 Dang, 2020, Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression, Aging Cell, 19, 10.1111/acel.13060 Manka, 2019, Fibrosis in chronic liver disease: an update on diagnostic and treatment modalities, Drugs, 79, 903, 10.1007/s40265-019-01126-9 Collard, 2010, The age of idiopathic pulmonary fibrosis, Am. J. Respir. Crit. Care Med., 181, 771, 10.1164/rccm.201001-0049ED Graney, 2018, Impact of novel antifibrotic therapy on patient outcomes in idiopathic pulmonary fibrosis: patient selection and perspectives, Patient Relat. Outcome Meas., 9, 321, 10.2147/PROM.S144425 Kolilekas, 2019, Existing and emerging treatments for idiopathic pulmonary fibrosis, Expert Rev. Respir. Med., 13, 229, 10.1080/17476348.2019.1568244 Zhao, 2021, L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction, Korean J. Intern. Med., 36, S180, 10.3904/kjim.2019.413 Zhang, 2018, Rhubarb protect against tubulointerstitial fibrosis by inhibiting TGF-β/Smad pathway and improving abnormal metabolome in chronic kidney disease, Front. Pharmacol., 9, 1029, 10.3389/fphar.2018.01029 Maddu, 2015, Review of lithium effects on immune cells, Immunopharmacol. Immunotoxicol., 37, 111, 10.3109/08923973.2014.998369 Desdín-Micó, 2020, T cells with dysfunctional mitochondria induce multimorbidity and premature senescence, Science, 368, 1371, 10.1126/science.aax0860 Bharath, 2020, Metformin enhances autophagy and normalizes mitochondrial function to alleviate aging-associated inflammation, Cell Metab., 32, 44, 10.1016/j.cmet.2020.04.015 Zhang, 2017, Effects of acarbose on the gut microbiota of prediabetic patients: a randomized, double-blind, controlled crossover trial, Diabetes Ther., 8, 293, 10.1007/s13300-017-0226-y Biagi, 2016, Gut microbiota and extreme longevity, Curr. Biol., 26, 1480, 10.1016/j.cub.2016.04.016 Schwalfenberg, 2017, Vitamins K1 and K2: the emerging group of vitamins required for human health, J. Nutr. Metab., 2017, 10.1155/2017/6254836 Matt, 2018, Butyrate and dietary soluble fiber improve neuroinflammation associated with aging in mice, Front. Immunol., 9, 1832, 10.3389/fimmu.2018.01832 Wu, 2018, Effects of the intestinal microbial metabolite butyrate on the development of colorectal cancer, J. Cancer, 9, 2510, 10.7150/jca.25324 Boehme, 2020, Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome, Mol. Psychiatry, 25, 2567, 10.1038/s41380-019-0425-1 Proshkina, 2020, Terpenoids as potential geroprotectors, Antioxidants (Basel), 9, 529, 10.3390/antiox9060529 Toyama, 2013, Protein homeostasis: live long, won’t prosper, Nat. Rev. Mol. Cell Biol., 14, 55, 10.1038/nrm3496 Barbosa, 2018, Hallmarks of aging: an autophagic perspective, Front. Endocrinol., 9, 790, 10.3389/fendo.2018.00790