Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures

Author(s): Amin Gasmi, Salvatore Chirumbolo, Massimiliano Peana, Pavan Kumar Mujawdiya, Maryam Dadar, Alain Menzel and Geir Bjørklund*

Volume 28, Issue 8, 2021

Published on: 17 September, 2020

Page: [1471 - 1488] Pages: 18

DOI: 10.2174/0929867327999200917150652

Price: $65


Human life expectancy is increasing significantly over time thanks to the improved possibility for people to take care of themselves and the higher availability of food, drugs, hygiene, services, and assistance. The increase in the average age of the population worldwide is, however, becoming a real concern, since aging is associated with the rapid increase in chronic inflammatory pathologies and degenerative diseases, very frequently dependent on senescent phenomena that occur alongside with senescence. Therefore, the search for reliable biomarkers that can diagnose the possible onset or predict the risk of developing a disease associated with aging is a crucial target of current medicine. In this review, we construct a synopsis of the main addressable biomarkers to study the development of aging and the associated ailments.

Keywords: Aging, senescence, biomarkers, inflammation, neurodegeneration, ailments.

Olshansky, S.J.; Carnes, B.A. Inconvenient truths about human longevity. J. Gerontol. A. Biol. Sci. Med. Sci, 2019, 74(Supplement_1>), S7-S12.
[] [PMID: 31001621]
Dolgin, E. There’s no limit to longevity, says study that revives human lifespan debate. Nature, 2018, 559(7712), 14-15.
[] [PMID: 29968831]
Rafi, M.A.; Alavi, A. Debate on human aging and lifespan. Bioimpacts, 2017, 7(3), 135-137.
[] [PMID: 29159140]
Liu, K.; Chen, Y.; Lin, R.; Han, K. Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients. J. Infect., 2020, 80(6), e14-e18.
[] [PMID: 32171866]
Carioli, G.; Malvezzi, M.; Bertuccio, P.; Hashim, D.; Waxman, S.; Negri, E.; Boffetta, P.; La Vecchia, C. Cancer mortality in the elderly in 11 countries worldwide, 1970-2015. Ann. Oncol., 2019, 30(8), 1344-1355.
[] [PMID: 31147682]
Maggio, M.; Guralnik, J.M.; Longo, D.L.; Ferrucci, L. Interleukin-6 in aging and chronic disease: a magnificent pathway. J. Gerontol. A Biol. Sci. Med. Sci., 2006, 61(6), 575-584.
[] [PMID: 16799139]
Vgontzas, A.N.; Bixler, E.O.; Lin, H.M.; Prolo, P.; Trakada, G.; Chrousos, G.P. IL-6 and its circadian secretion in humans. Neuroimmunomodulation, 2005, 12(3), 131-140.
[] [PMID: 15905620]
Kaplanski, G.; Marin, V.; Montero-Julian, F.; Mantovani, A.; Farnarier, C. IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol., 2003, 24(1), 25-29.
[] [PMID: 12495721]
Van Epps, P.; Oswald, D.; Higgins, P.A.; Hornick, T.R.; Aung, H.; Banks, R.E.; Wilson, B.M.; Burant, C.; Graventstein, S.; Canaday, D.H. Frailty has a stronger association with inflammation than age in older veterans. Immun. Ageing, 2016, 13, 27.
[] [PMID: 27777599]
Yoshida, Y.; Tanaka, T. Interleukin 6 and rheumatoid arthritis. BioMed Res. Int., 2014., 2014698313.
[] [PMID: 24524085]
Godbout, J.P.; Johnson, R.W. Interleukin-6 in the aging brain. J. Neuroimmunol., 2004, 147(1-2), 141-144.
[] [PMID: 14741447]
Raz, N.; Lustig, C. Genetic variants and cognitive aging: destiny or a nudge? Psychol. Aging, 2014, 29(2), 359-362.
[] [PMID: 24956004]
Gabay, C. Interleukin-6 and chronic inflammation. Arthritis Res. Ther., 2006, 8(Suppl. 2), S3.
[] [PMID: 16899107]
Kamath, D.Y.; Xavier, D.; Sigamani, A.; Pais, P. High sensitivity C-reactive protein (hsCRP) & cardiovascular disease: an Indian perspective. Indian J. Med. Res., 2015, 142(3), 261-268.
[] [PMID: 26458341]
Boxer, R.S.; Dauser, D.A.; Walsh, S.J.; Hager, W.D.; Kenny, A.M. The association between vitamin D and inflammation with the 6-minute walk and frailty in patients with heart failure. J. Am. Geriatr. Soc., 2008, 56(3), 454-461.
[] [PMID: 18194227]
Adav, S.S.; Sze, S.K. Hypoxia-induced degenerative protein modifications associated with aging and age-associated disorders. Aging Dis., 2020, 11(2), 341-364.
[] [PMID: 32257546]
Ghodsi, R.; Kheirouri, S. Carnosine and advanced glycation end products: a systematic review. Amino Acids, 2018, 50(9), 1177-1186.
[] [PMID: 29858687]
Mayer, O.; Gelžinský, J.; Seidlerová, J.; Mateřánková, M.; Mareš, Š.; Svobodová, V.; Trefil, L.; Cífková, R.; Filipovský, J. The role of advanced glycation end products in vascular aging: which parameter is the most suitable as a biomarker? J. Hum. Hypertens., 2020.
[] [PMID: 32203073]
Almajwal, A.M.; Alam, I.; Abulmeaty, M.; Razak, S.; Pawelec, G.; Alam, W. Intake of dietary advanced glycation end products influences inflammatory markers, immune phenotypes, and antiradical capacity of healthy elderly in a little-studied population. Food Sci. Nutr., 2020, 8(2), 1046-1057.
[] [PMID: 32148813]
Bai, X. Biomarkers of aging. Adv. Exp. Med. Biol., 2018, 1086, 217-234.
[] [PMID: 30232762]
Wagner, K.H.; Cameron-Smith, D.; Wessner, B.; Franzke, B. Biomarkers of aging: from function to molecular biology. Nutrients, 2016, 8(6), E338.
[] [PMID: 27271660]
Xu, K.; Guo, Y.; Li, Z.; Wang, Z. Aging biomarkers and novel targets for anti-aging interventions. Adv. Exp. Med. Biol., 2019, 1178, 39-56.
[] [PMID: 31493221]
Pinti, M.; Appay, V.; Campisi, J.; Frasca, D.; Fülöp, T.; Sauce, D.; Larbi, A.; Weinberger, B.; Cossarizza, A. Aging of the immune system: focus on inflammation and vaccination. Eur. J. Immunol., 2016, 46(10), 2286-2301.
[] [PMID: 27595500]
Akbar, A.N.; Henson, S.M.; Lanna, A. Senescence of T lymphocytes: implications for enhancing human immunity. Trends Immunol., 2016, 37(12), 866-876.
[] [PMID: 27720177]
Alawam, A.S.; Anderson, G.; Lucas, B. Generation and regeneration of thymic epithelial cells. Front. Immunol., 2020, 11, 858.
[] [PMID: 32457758]
McElhaney, J.E.; Verschoor, C.P.; Andrew, M.K.; Haynes, L.; Kuchel, G.A.; Pawelec, G. The immune response to influenza in older humans: beyond immune senescence. Immun. Ageing, 2020, 17, 10.
[] [PMID: 32399058]
Vitale, B. Holistic Approach to the immunobiology of aging (view on the turn of millenium). Acta Clin. Croat., 2019, 58(Suppl. 1), 29-34.
[] [PMID: 31741556]
Sansoni, P.; Vescovini, R.; Fagnoni, F.; Biasini, C.; Zanni, F.; Zanlari, L.; Telera, A.; Lucchini, G.; Passeri, G.; Monti, D.; Franceschi, C.; Passeri, M. The immune system in extreme longevity. Exp. Gerontol., 2008, 43(2), 61-65.
[] [PMID: 17870272]
Cossarizza, A.; Ortolani, C.; Paganelli, R.; Barbieri, D.; Monti, D.; Sansoni, P.; Fagiolo, U.; Castellani, G.; Bersani, F.; Londei, M.; Franceschi, C. CD45 isoforms expression on CD4+ and CD8+ T cells throughout life, from newborns to centenarians: implications for T cell memory. Mech. Ageing Dev., 1996, 86(3), 173-195.
[] [PMID: 8733112]
Wang, J.; Geiger, H.; Rudolph, K.L. Immunoaging induced by hematopoietic stem cell aging. Curr. Opin. Immunol., 2011, 23(4), 532-536.
[] [PMID: 21872769]
Losappio, V.; Franzin, R.; Infante, B.; Godeas, G.; Gesualdo, L.; Fersini, A.; Castellano, G.; Stallone, G. Molecular mechanisms of premature aging in hemodialysis: the Complex interplay between innate and adaptive immune dysfunction. Int. J. Mol. Sci., 2020, 21(10), E3422.
[] [PMID: 32408613]
Witkowski, J.M.; Larbi, A.; Le Page, A.; Fülöp, T. Natural killer cells, aging, and vaccination. Interdiscip. Top. Gerontol. Geriatr., 2020, 43, 18-35.
[] [PMID: 32294658]
Hagen, M.; Derudder, E. Inflammation and the alteration of B-cell physiology in aging. Gerontology, 2020, 66(2), 105-113.
[] [PMID: 31553969]
Frasca, D.; Blomberg, B.B. Adipose tissue inflammation induces B cell inflammation and decreases B cell function in aging. Front. Immunol., 2017, 8, 1003.
[] [PMID: 28894445]
Poinsatte, K. Smith, E.E.; Torres, V.O.; Ortega, S.B.; Huebinger, R.M.; Cullum, C.M.; Monson, N.L.; Zhang, R.; Stowe, A.M. T and B cell subsets differentially correlate with amyloid deposition and neurocognitive function in patients with amnestic mild cognitive impairment after one year of physical activity. Exerc. Immunol. Rev., 2019, 25, 34-49.
[PMID: 30785868]
Yanes, R.E.; Gustafson, C.E.; Weyand, C.M.; Goronzy, J.J. Lymphocyte generation and population homeostasis throughout life. Semin. Hematol., 2017, 54(1), 33-38.
[] [PMID: 28088985]
Ademokun, A.; Wu, Y.C.; Dunn-Walters, D. The ageing B cell population: composition and function. Biogerontology, 2010, 11(2), 125-137.
[] [PMID: 19937382]
Frasca, D.; Diaz, A.; Romero, M.; Phillips, M.; Mendez, N.V.; Landin, A.M.; Blomberg, B.B. Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine. Int. Immunol., 2012, 24(3), 175-182.
[] [PMID: 22281510]
Frasca, D.; Landin, A.M.; Lechner, S.C.; Ryan, J.G.; Schwartz, R.; Riley, R.L.; Blomberg, B.B. Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells. J. Immunol., 2008, 180(8), 5283-5290.
[] [PMID: 18390709]
Shi, Y.; Yamazaki, T.; Okubo, Y.; Uehara, Y.; Sugane, K.; Agematsu, K. Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J. Immunol., 2005, 175(5), 3262-3267.
[] [PMID: 16116217]
Salvioli, S.; Monti, D.; Lanzarini, C.; Conte, M.; Pirazzini, C.; Bacalini, M.G.; Garagnani, P.; Giuliani, C.; Fontanesi, E.; Ostan, R.; Bucci, L.; Sevini, F.; Yani, S.L.; Barbieri, A.; Lomartire, L.; Borelli, V.; Vianello, D.; Bellavista, E.; Martucci, M.; Cevenini, E.; Pini, E.; Scurti, M.; Biondi, F.; Santoro, A.; Capri, M.; Franceschi, C. Immune system, cell senescence, aging and longevity--inflamm-aging reappraised. Curr. Pharm. Des., 2013, 19(9), 1675-1679.
[PMID: 23589904]
Ovadya, Y.; Landsberger, T.; Leins, H.; Vadai, E.; Gal, H.; Biran, A.; Yosef, R.; Sagiv, A.; Agrawal, A.; Shapira, A.; Windheim, J.; Tsoory, M.; Schirmbeck, R.; Amit, I.; Geiger, H.; Krizhanovsky, V. Impaired immune surveillance accelerates accumulation of senescent cells and aging. Nat. Commun., 2018, 9(1), 5435.
[] [PMID: 30575733]
Smith, K.J.; Gavey, S. RIddell, N.E.; Kontari, P.; Victor, C. The association between loneliness, social isolation and inflammation: A systematic review and meta-analysis. Neurosci. Biobehav. Rev., 2020, 112, 519-541.
[] [PMID: 32092313]
Chambers, E.S.; Akbar, A.N. Can blocking inflammation enhance immunity during aging? J. Allergy Clin. Immunol., 2020, 145(5), 1323-1331.
[] [PMID: 32386656]
Fossati, C.; Torre, G.; Borrione, P.; Giombini, A.; Fagnani, F.; Turchetta, M.; Albo, E.; Casasco, M.; Parisi, A.; Pigozzi, F. Biohumoral Indicators Influenced by Physical Activity in the Elderly. J. Clin. Med., 2020, 9(4), E1115.
[] [PMID: 32295038]
Erol, A. Interleukin-6 (IL-6) is still the leading biomarker of the metabolic and aging related disorders. Med. Hypotheses, 2007, 69(3), 708.
[] [PMID: 17335991]
Straub, R.H.; Buttgereit, F.; Cutolo, M. Alterations of the hypothalamic-pituitary-adrenal axis in systemic immune diseases - a role for misguided energy regulation. Clin. Exp. Rheumatol., 2011, 29(5)(Suppl. 68), S23-S31.
[PMID: 22018180]
Padilha, H.G.; Crispim, C.A.; Zimberg, I.Z.; De-Souza, D.A.; Waterhouse, J.; Tufik, S.; de-Mello, M.T. A link between sleep loss, glucose metabolism and adipokines. Braz. J. Med. Biol. Res., 2011, 44(10), 992-999.
[] [PMID: 21881808]
Lustgarten, M.S.; Fielding, R.A. Metabolites associated with circulating interleukin-6 in older adults. J. Gerontol. A Biol. Sci. Med. Sci., 2017, 72(9), 1277-1283.
[] [PMID: 26975982]
Cardoso, A.L.; Fernandes, A.; Aguilar-Pimentel, J.A.; de Angelis, M.H.; Guedes, J.R.; Brito, M.A.; Ortolano, S.; Pani, G.; Athanasopoulou, S.; Gonos, E.S.; Schosserer, M.; Grillari, J.; Peterson, P.; Tuna, B.G.; Dogan, S.; Meyer, A.; van Os, R.; Trendelenburg, A.U. Towards frailty biomarkers: candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res. Rev., 2018, 47, 214-277.
[] [PMID: 30071357]
Semmarath, W.; Seesen, M.; Yodkeeree, S.; Sapbamrer, R.; Ayood, P.; Malasao, R.; Siviroj, P.; Limtrakul Dejkriengkraikul, P. The Association between frailty indicators and blood-based biomarkers in early-old community dwellers of Thailand. Int. J. Environ. Res. Public Health, 2019, 16(18), E3457.
[] [PMID: 31533354]
Milan-Mattos, J.C.; Anibal, F.F.; Perseguini, N.M.; Minatel, V.; Rehder-Santos, P.; Castro, C.A.; Vasilceac, F.A.; Mattiello, S.M.; Faccioli, L.H.; Catai, A.M. Effects of natural aging and gender on pro-inflammatory markers. Braz. J. Med. Biol. Res., 2019, 52(9), e8392.
[] [PMID: 31411315]
Corley, J.; Shivappa, N.; Hébert, J.R.; Starr, J.M.; Deary, I.J. Associations between dietary inflammatory index scores and inflammatory biomarkers among older adults in the Lothian birth Cohort 1936 study. J. Nutr. Health Aging, 2019, 23(7), 628-636.
[] [PMID: 31367727]
Corlier, F.; Hafzalla, G.; Faskowitz, J.; Kuller, L.H.; Becker, J.T.; Lopez, O.L.; Thompson, P.M.; Braskie, M.N. Systemic inflammation as a predictor of brain aging: contributions of physical activity, metabolic risk, and genetic risk. Neuroimage, 2018, 172, 118-129.
[] [PMID: 29357308]
Tang, Y.; Fung, E.; Xu, A.; Lan, H.Y. C-reactive protein and ageing. Clin. Exp. Pharmacol. Physiol., 2017, 44(Suppl. 1), 9-14.
[] [PMID: 28378496]
Slevin, M.; Molins, B. Editorial: C-reactive protein in age-related disorders. Front. Immunol., 2018, 9, 2745.
[] [PMID: 30524450]
Chirco, K.R.; Potempa, L.A. C-reactive protein as a mediator of complement activation and Inflammatory signaling in age-related macular degeneration. Front. Immunol., 2018, 9, 539.
[] [PMID: 29599782]
Du Clos, T.W. Pentraxins: structure, function, and role in inflammation. ISRN Inflamm., 2013, 2013, 379040.
[] [PMID: 24167754]
Puzianowska-Kuźnicka, M.; Owczarz, M.; Wieczorowska-Tobis, K.; Nadrowski, P.; Chudek, J.; Slusarczyk, P.; Skalska, A.; Jonas, M.; Franek, E.; Mossakowska, M. Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study. Immun. Ageing, 2016, 13, 21.
[] [PMID: 27274758]
Zheng, F.; Xie, W. High-sensitivity C-reactive protein and cognitive decline: the English longitudinal study of ageing. Psychol. Med., 2018, 48(8), 1381-1389.
[] [PMID: 29108529]
Cleveland Clinic NT-proB-type Natriuretic Peptide (BNP). Available at: (Accessed date: April 2013).
Pan, Y.; Li, D.; Ma, J.; Shan, L.; Wei, M. NT-proBNP test with improved accuracy for the diagnosis of chronic heart failure. Medicine (Baltimore), 2017, 96(51), e9181.
[] [PMID: 29390456]
Di Castelnuovo, A.; Veronesi, G.; Costanzo, S.; Zeller, T.; Schnabel, R.B.; de Curtis, A.; Salomaa, V.; Borchini, R.; Ferrario, M.; Giampaoli, S.; Kee, F.; Söderberg, S.; Niiranen, T.; Kuulasmaa, K.; de Gaetano, G.; Donati, M.B.; Blankenberg, S.; Iacoviello, L. BiomarCaRE Investigators. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the risk of stroke. Stroke, 2019, 50(3), 610-617.
[] [PMID: 30786848]
Vergaro, G.; Januzzi, J.L., Jr; Cohen Solal, A.; Aimo, A.; Arzilli, C.; Zyw, L.; Valleggi, A.; Giannoni, A.; Prontera, C.; Barison, A.; Poletti, R.; Gabutti, A.; Mammini, C.; Passino, C.; Emdin, M. NT-proBNP prognostic value is maintained in elderly and very elderly patients with chronic systolic heart failure. Int. J. Cardiol., 2018, 271, 324-330.
[] [PMID: 30223365]
Su, Q.; Liu, H.; Zhang, X.; Dang, W.; Liu, R.; Zhao, X.; Yuan, X.; Qin, Y.; Zhang, J.; Chen, C.; Xia, Y. Diagnostic values of NT-proBNP in acute dyspnea among elderly patients. Int. J. Clin. Exp. Pathol., 2015, 8(10), 13471-13476.
[PMID: 26722559]
Seidler, S.; Zimmermann, H.W.; Bartneck, M.; Trautwein, C.; Tacke, F. Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults. BMC Immunol., 2010, 11, 30.
[] [PMID: 20565954]
Geissmann, F.; Manz, M.G.; Jung, S.; Sieweke, M.H.; Merad, M.; Ley, K. Development of monocytes, macrophages, and dendritic cells. Science, 2010, 327(5966), 656-661.
[] [PMID: 20133564]
Valiathan, R.; Ashman, M.; Asthana, D. Effects of ageing on the immune system: infants to elderly. Scand. J. Immunol., 2016, 83(4), 255-266.
[] [PMID: 26808160]
Zawada, A.M.; Rogacev, K.S.; Schirmer, S.H.; Sester, M.; Böhm, M.; Fliser, D.; Heine, G.H. Monocyte heterogeneity in human cardiovascular disease. Immunobiology, 2012, 217(12), 1273-1284.
[] [PMID: 22898391]
Waterhouse, D.F.; Cahill, R.A.; Sheehan, F.; McCreery, C. Prediction of calculated future cardiovascular disease by monocyte count in an asymptomatic population. Vasc. Health Risk Manag., 2008, 4(1), 177-187.
[] [PMID: 18629357]
Samson, L.D.; Boots, A.M.H.; Verschuren, W.M.M.; Picavet, H.S.J.; Engelfriet, P.; Buisman, A.M. Frailty is associated with elevated CRP trajectories and higher numbers of neutrophils and monocytes. Exp. Gerontol., 2019, 125, 110674.
[] [PMID: 31336145]
Aminzadeh, Z.; Parsa, E. Relationship between age and peripheral white blood cell count in Patients with Sepsis. Int. J. Prev. Med., 2011, 2(4), 238-242.
[PMID: 22174963]
McGrath, C.R.; Hitchcock, D.C.; van Assendelft, O.W. Total white blood cell counts for persons ages 1-74 years with differential leukocyte counts for adults ages 25-74 years: United States, 1971-75. Vital Health Stat. 11, 1982, (220), 1-36.
[PMID: 7064358]
McArthur, W.P.; Bloom, K.; Taylor, M.; Wheeler, T.; Smith, J.; Magnusson, N.I. Peripheral blood leukocyte populations in the elderly with and without periodontal disease. J. Clin. Periodontol., 1996, 23(9), 846-852.
[] [PMID: 8891936]
Velioglu, Y.; Yuksel, A. Complete blood count parameters in peripheral arterial disease. Aging Male, 2019, 22(3), 187-191.
[] [PMID: 30924393]
Karino, S.; Willcox, B.J.; Fong, K.; Lo, S.; Abbott, R.; Masaki, K.H. Total and differential white blood cell counts predict eight-year incident coronary heart disease in elderly Japanese-American men: the Honolulu Heart Program. Atherosclerosis, 2015, 238(2), 153-158.
[] [PMID: 25514532]
Verdoia, M.; Barbieri, L.; Di Giovine, G.; Marino, P.; Suryapranata, H.; De Luca, G. Novara Atherosclerosis Study Group (NAS). Neutrophil to lymphocyte ratio and the extent of coronary artery disease: results from a large Cohort Study. Angiology, 2016, 67(1), 75-82.
[] [PMID: 25818102]
Chen, Y.; Zhang, Y.; Zhao, G.; Chen, C.; Yang, P.; Ye, S.; Tan, X. Difference in leukocyte composition between women before and after menopausal age, and distinct sexual dimorphism. PLoS One, 2016, 11(9), e0162953.
[] [PMID: 27657912]
Dong, X.; Nao, J.; Shi, J.; Zheng, D. Predictive value of routine peripheral blood biomarkers in Alzheimer’s disease. Front. Aging Neurosci., 2019, 11, 332.
[] [PMID: 31866854]
Cruz-Ramos, M.; Del Puerto-Nevado, L.; Zheng, B.; López-Bajo, R.; Cebrian, A.; Rodríguez-Remirez, M.; García-García, L.; Solanes-Casado, S.; García-Foncillas, J. Prognostic significance of neutrophil-to lymphocyte ratio and platelet-to lymphocyte ratio in older patients with metastatic colorectal cancer. J. Geriatr. Oncol., 2019, 10(5), 742-748.
[] [PMID: 30327283]
Nishijima, T.F.; Deal, A.M.; Williams, G.R.; Guerard, E.J.; Nyrop, K.A.; Muss, H.B. Frailty and inflammatory markers in older adults with cancer. Aging (Albany NY), 2017, 9(3), 650-664.
[] [PMID: 28273043]
Davis, J.L.; Moutinho, V., Jr; Panageas, K.S.; Coit, D.G. A peripheral blood biomarker estimates probability of survival: the neutrophil-lymphocyte ratio in noncancer patients. Biomarkers Med., 2016, 10(9), 953-957.
[] [PMID: 27537355]
Walsh, J.R. Hematologic disorders in the elderly. West. J. Med., 1981, 135(6), 446-454.
[PMID: 6801866]
Carmel, R. Nutritional anemias and the elderly. Semin. Hematol., 2008, 45(4), 225-234.
[] [PMID: 18809092]
Bron, D.; Ades, L.; Fulop, T.; Goede, V.; Stauder, R. Elderly task force in hematology EHA SWG. Aging and blood disorders: new perspectives, new challenges. Haematologica, 2015, 100(4), 415-417.
[] [PMID: 25828087]
Patel, K.V.; Semba, R.D.; Ferrucci, L.; Newman, A.B.; Fried, L.P.; Wallace, R.B.; Bandinelli, S.; Phillips, C.S.; Yu, B.; Connelly, S.; Shlipak, M.G.; Chaves, P.H.; Launer, L.J.; Ershler, W.B.; Harris, T.B.; Longo, D.L.; Guralnik, J.M. Red cell distribution width and mortality in older adults: a meta-analysis. J. Gerontol. A Biol. Sci. Med. Sci., 2010, 65(3), 258-265.
[] [PMID: 19880817]
Lippi, G.; Salvagno, G.L.; Guidi, G.C. Red blood cell distribution width is significantly associated with aging and gender. Clin. Chem. Lab. Med., 2014, 52(9), e197-e199.
[] [PMID: 24897405]
Balistreri, C.R.; Pisano, C.; Bertoldo, F.; Massoud, R.; Dolci, S.; Ruvolo, G. red blood cell distribution width, vascular aging biomarkers, and endothelial progenitor cells for predicting vascular aging and diagnosing/prognosing age-related degenerative arterial diseases. Rejuvenation Res., 2019, 22(5), 399-408.
[] [PMID: 30572793]
Pilling, L.C.; Atkins, J.L.; Kuchel, G.A.; Ferrucci, L.; Melzer, D. Red cell distribution width and common disease onsets in 240,477 healthy volunteers followed for up to 9 years. PLoS One, 2018, 13(9), e0203504.
[] [PMID: 30212481]
Tajuddin, S.M.; Nalls, M.A.; Zonderman, A.B.; Evans, M.K. Association of red cell distribution width with all-cause and cardiovascular-specific mortality in African American and white adults: a prospective cohort study. J. Transl. Med., 2017, 15(1), 208.
[] [PMID: 29029617]
Choi, J.W.; Pai, S.H.; Im, M.W.; Kim, S.K. Change in transferrin receptor concentrations with age. Clin. Chem., 1999, 45(9), 1562-1563.
[] [PMID: 10471662]
Bloomer, S.A.; Han, O.; Kregel, K.C.; Brown, K.E. Altered expression of iron regulatory proteins with aging is associated with transient hepatic iron accumulation after environmental heat stress. Blood Cells Mol. Dis., 2014, 52(1), 19-26.
[] [PMID: 23900040]
Ambrosy, A.P.; Fitzpatrick, J.K.; Tabada, G.H.; Gurwitz, J.H.; Artz, A.; Schrier, S.L.; Rao, S.V.; Reynolds, K.; Smith, D.H.; Peterson, P.N.; Fortmann, S.P.; Sung, S.H.; Cohen, H.J.; Go, A.S.; Consortium, R.H.I.P. RBC HEART Investigators/PACTTE Consortium. A reduced transferrin saturation is independently associated with excess morbidity and mortality in older adults with heart failure and incident anemia. Int. J. Cardiol., 2020, 309, 95-99.
[] [PMID: 32201101]
El Gayar, N.H.; Deghady, A.A. Iron status in healthy elderly people: an evaluation of the role of soluble transferrin receptors in elderly. Egypt J. Obes. Diabetes Endocrinol., 2015, 1(3), 153-158.
Gamaldo, A.A.; Ferrucci, L.; Rifkind, J.M.; Zonderman, A.B. Age-related changes in mean corpuscular volume in adult whites and African Americans. J. Am. Geriatr. Soc., 2011, 59(9), 1763-1764.
[] [PMID: 22136544]
Mahlknecht, U.; Kaiser, S. Age-related changes in peripheral blood counts in humans. Exp. Ther. Med., 2010, 1(6), 1019-1025.
[] [PMID: 22993635]
Gamaldo, A.A.; Ferrucci, L.; Rifkind, J.; Longo, D.L.; Zonderman, A.B. Relationship between mean corpuscular volume and cognitive performance in older adults. J. Am. Geriatr. Soc., 2013, 61(1), 84-89.
[] [PMID: 23301873]
Frąckiewicz, J.; Włodarek, D.; Brzozowska, A.; Wierzbicka, E.; Słowińska, M.A.; Wądołowska, L.; Kałuża, J. Hematological parameters and all-cause mortality: a prospective study of older people. Aging Clin. Exp. Res., 2018, 30(5), 517-526.
[] [PMID: 28664457]
Goodnough, L.T.; Schrier, S.L. Evaluation and management of anemia in the elderly. Am. J. Hematol., 2014, 89(1), 88-96.
[] [PMID: 24122955]
Salive, M.E.; Cornoni-Huntley, J.; Guralnik, J.M.; Phillips, C.L.; Wallace, R.B.; Ostfeld, A.M.; Cohen, H.J. Anemia and hemoglobin levels in older persons: relationship with age, gender, and health status. J. Am. Geriatr. Soc., 1992, 40(5), 489-496.
[] [PMID: 1634703]
Taniguchi, Y.; Kitamura, A.; Kaito, S.; Yokoyama, Y.; Yokota, I.; Shinozaki, T.; Seino, S.; Murayama, H.; Matsuyama, Y.; Ikeuchi, T.; Fujiwara, Y.; Shinkai, S. Albumin and hemoglobin trajectories and incident disabling dementia in community-dwelling Older Japanese. Dement. Geriatr. Cogn. Disord., 2019, 47(4-6), 233-242.
[] [PMID: 31315125]
Shakeri, H.; Lemmens, K.; Gevaert, A.B.; De Meyer, G.R.Y.; Segers, V.F.M. Cellular senescence links aging and diabetes in cardiovascular disease. Am. J. Physiol. Heart Circ. Physiol., 2018, 315(3), H448-H462.
[] [PMID: 29750567]
Dhaliwal, R.; Rosen, C.J. Type 2 diabetes and aging: a not so sweet scenario for bone. Horm. Metab. Res., 2016, 48(11), 771-778.
[] [PMID: 27728926]
Bispham, J.A.; Hughes, A.S.; Driscoll, K.A.; McAuliffe-Fogarty, A.H. Novel challenges in aging with type 1 diabetes. Curr. Diab. Rep., 2020, 20(5), 15.
[] [PMID: 32198703]
Bentley, R.A.; Ross, C.N.; O’Brien, M.J. Obesity, metabolism, and aging: a multiscalar approach. Prog. Mol. Biol. Transl. Sci., 2018, 155, 25-42.
[] [PMID: 29653680]
Syed, I.A. Glycated haemoglobin; past, present, and future are we ready for the change. J. Pak. Med. Assoc., 2011, 61(4), 383-388.
[PMID: 21465979]
Suvarna, HI, S.; Moodithaya, S.; Sharma, R. Metabolic and cardiovascular ageing indices in relation to glycated haemoglobin in healthy and diabetic subjects. Curr. Aging Sci., 2017, 10(3), 201-210.
[ ] [PMID: 28215180]
WHO. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus: abbreviated report of a WHO consultation. Geneva: World Health Organization, 2011. Available at: (Accessed Date: 1 March 2021).
Ma, Q.; Liu, H.; Xiang, G.; Shan, W.; Xing, W. Association between glycated hemoglobin A1c levels with age and gender in Chinese adults with no prior diagnosis of diabetes mellitus. Biomed. Rep., 2016, 4(6), 737-740.
[] [PMID: 27284415]
Koyama, H.; Yamamoto, H.; Nishizawa, Y. RAGE and soluble RAGE: potential therapeutic targets for cardiovascular diseases. Mol. Med., 2007, 13(11-12), 625-635.
[] [PMID: 17932553]
Lorenzi, R.; Grossin, N.; Lambert, M.; Daroux, M.; Adjoutah, Z.; Flahaut, C.; Jacolot, P.; Tessier, F.J.; Lefranc, D.; Desremaux, P.; Dubucquoi, S.; Boulanger, E. Soluble form of receptor for advanced glycation end-products (sRAGE): do sRAGE ligands or anti-sRAGE auto-antibodies interfere with sRAGE quantification? Ann. Clin. Biochem., 2014, 51(Pt 2), 248-257.
[] [PMID: 23982266]
Peng, Y.; Park, H.S.; Tang, L.A.; Horwitz, N.; Lin, L. Generation of sRAGEhigh transgenic mice to study inflammaging. Front. Biosci., 2019, 24, 555-563.
[] [PMID: 30468673]
Forbes, J.M.; Thorpe, S.R.; Thallas-Bonke, V.; Pete, J.; Thomas, M.C.; Deemer, E.R.; Bassal, S.; El-Osta, A.; Long, D.M.; Panagiotopoulos, S.; Jerums, G.; Osicka, T.M.; Cooper, M.E. Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy. J. Am. Soc. Nephrol., 2005, 16(8), 2363-2372.
[] [PMID: 15930093]
Juranek, J.K.; Daffu, G.K.; Geddis, M.S.; Li, H.; Rosario, R.; Kaplan, B.J.; Kelly, L.; Schmidt, A.M. Soluble RAGE treatment delays progression of amyotrophic lateral sclerosis in SOD1 Mice. Front. Cell. Neurosci., 2016, 10, 117.
[] [PMID: 27242430]
Zhang, F.; Su, X.; Huang, G.; Xin, X.F.; Cao, E.H.; Shi, Y.; Song, Y. sRAGE alleviates neutrophilic asthma by blocking HMGB1/RAGE signalling in airway dendritic cells. Sci. Rep., 2017, 7(1), 14268.
[] [PMID: 29079726]
Prasad, K. Is there any evidence that AGE/sRAGE is a universal biomarker/risk marker for diseases? Mol. Cell. Biochem., 2019, 451(1-2), 139-144.
[] [PMID: 29961210]
Gulcelik, N.E.; Halil, M.; Ariogul, S.; Usman, A. Adipocytokines and aging: adiponectin and leptin. Minerva Endocrinol., 2013, 38(2), 203-210.
[PMID: 23732375]
Arai, Y.; Hirose, N. Adiponectin and healthy aging in centenarians. Anti-Aging Med, 2012, 9(1), 1-5.
Kizer, J.R.; Arnold, A.M.; Strotmeyer, E.S.; Ives, D.G.; Cushman, M.; Ding, J.; Kritchevsky, S.B.; Chaves, P.H.; Hirsch, C.H.; Newman, A.B. Change in circulating adiponectin in advanced old age: determinants and impact on physical function and mortality. The Cardiovascular Health Study All Stars Study. J. Gerontol. A Biol. Sci. Med. Sci., 2010, 65(11), 1208-1214.
[] [PMID: 20616148]
Song, S.H.; Oh, T.R.; Choi, H.S.; Kim, C.S.; Ma, S.K.; Oh, K.H.; Ahn, C.; Kim, S.W.; Bae, E.H. High serum adiponectin as a biomarker of renal dysfunction: results from the KNOW-CKD study. Sci. Rep., 2020, 10(1), 5598.
[] [PMID: 32221363]
Mirza, S.; Qu, H.Q.; Li, Q.; Martinez, P.J.; Rentfro, A.R.; McCormick, J.B.; Fisher-Hoch, S.P. Adiponectin/leptin ratio and metabolic syndrome in a Mexican American population. Clin. Invest. Med., 2011, 34(5), E290.
[] [PMID: 21968271]
Frühbeck, G.; Catalán, V.; Rodríguez, A.; Gómez-Ambrosi, J. Adiponectin-leptin ratio: a promising index to estimate adipose tissue dysfunction. Relation with obesity-associated cardiometabolic risk. Adipocyte, 2018, 7(1), 57-62.
[] [PMID: 29205099]
Ashpole, N.M.; Sanders, J.E.; Hodges, E.L.; Yan, H.; Sonntag, W.E. Growth hormone, insulin-like growth factor-1 and the aging brain. Exp. Gerontol., 2015, 68, 76-81.
[] [PMID: 25300732]
Bartke, A.; Chandrashekar, V.; Dominici, F.; Turyn, D.; Kinney, B.; Steger, R.; Kopchick, J.J. Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights. Biogerontology, 2003, 4(1), 1-8.
[] [PMID: 12652183]
Wrigley, S.; Arafa, D.; Tropea, D. Insulin-like growth factor 1: at the crossroads of brain development and aging. Front. Cell. Neurosci., 2017, 11, 14.
[] [PMID: 28203146]
Mesa-Herrera, F.; Taoro-González, L.; Valdés-Baizabal, C.; Diaz, M.; Marín, R. Lipid and lipid raft alteration in aging and neurodegenerative diseases: a window for the development of new biomarkers. Int. J. Mol. Sci., 2019, 20(15), E3810.
[] [PMID: 31382686]
Yavuzer, H.; Yavuzer, S.; Cengiz, M.; Erman, H.; Doventas, A.; Balci, H.; Erdincler, D.S.; Uzun, H. Biomarkers of lipid peroxidation related to hypertension in aging. Hypertens. Res., 2016, 39(5), 342-348.
[] [PMID: 26763852]
Petrocelli, J.J.; McKenzie, A.I.; Mahmassani, Z.S.; Reidy, P.T.; Stoddard, G.J.; Poss, A.M.; Holland, W.L.; Summers, S.A.; Drummond, M.J. Ceramide biomarkers predictive of cardiovascular disease risk increase in healthy older adults after bed rest. J. Gerontol. A Biol. Sci. Med. Sci., 2020, glaa072.
[] [PMID: 32215553]
Mohanty, B.P.; Bhattacharjee, S.; Paria, P.; Mahanty, A.; Sharma, A.P. Lipid biomarkers of lens aging. Appl. Biochem. Biotechnol., 2013, 169(1), 192-200.
[] [PMID: 23179275]
Tabas, I. Cholesterol in health and disease. J. Clin. Invest., 2002, 110(5), 583-590.
[] [PMID: 12208856]
Tall, A.R. An overview of reverse cholesterol transport. Eur. Heart J., 1998, 19(Suppl. A), A31-A35.
[PMID: 9519340]
Kreisberg, R.A.; Kasim, S. Cholesterol metabolism and aging. Am. J. Med., 1987, 82(1B), 54-60.
[] [PMID: 3544833]
Parini, P.; Angelin, B.; Rudling, M. Cholesterol and lipoprotein metabolism in aging: reversal of hypercholesterolemia by growth hormone treatment in old rats. Arterioscler. Thromb. Vasc. Biol., 1999, 19(4), 832-839.
[] [PMID: 10195906]
Samadi, A.; Sabuncuoglu, S.; Samadi, M.; Isikhan, S.Y.; Chirumbolo, S.; Peana, M.; Lay, I.; Yalcinkaya, A.; Bjørklund, G. A Comprehensive review on oxysterols and related diseases. Curr. Med. Chem., 2021, 28(1), 110-136.
[] [PMID: 32175830]
Bradford, S.; Ramsetty, A.; Bragg, S.; Bain, J. Endocrine conditions in older adults: anti-aging therapies. FP Essent., 2018, 474, 33-38.
[PMID: 30427651]
Umansky, S. Aging and aging-associated diseases: a microRNA-based endocrine regulation hypothesis. Aging (Albany NY), 2018, 10(10), 2557-2569.
[] [PMID: 30375982]
Clegg, A.; Hassan-Smith, Z. Frailty and the endocrine system. Lancet Diabetes Endocrinol., 2018, 6(9), 743-752.
[] [PMID: 30017798]
Maggio, M.; Lauretani, F.; Basaria, S.; Ceda, G.P.; Bandinelli, S.; Metter, E.J.; Bos, A.J.; Ruggiero, C.; Ceresini, G.; Paolisso, G.; Artoni, A.; Valenti, G.; Guralnik, J.M.; Ferrucci, L. Sex hormone binding globulin levels across the adult lifespan in women--the role of body mass index and fasting insulin. J. Endocrinol. Invest., 2008, 31(7), 597-601.
[] [PMID: 18787375]
Li, Y.; Li, X.; Fan, H.; Li, X.; Zhong, Y.; Cao, J.; Yu, D.; Zhang, M.; Wen, J.G.; Geng, L.; Suo, Z. Age-dependent sex hormone-binding globulin expression in male rat. Ultrastruct. Pathol., 2015, 39(2), 121-130.
[] [PMID: 25879298]
Cooper, L.A.; Page, S.T.; Amory, J.K.; Anawalt, B.D.; Matsumoto, A.M. The association of obesity with sex hormone-binding globulin is stronger than the association with ageing--implications for the interpretation of total testosterone measurements. Clin. Endocrinol. (Oxf.), 2015, 83(6), 828-833.
[] [PMID: 25777143]
Barrou, Z.; Charru, P.; Lidy, C. Dehydroepiandrosterone (DHEA) and aging. Arch. Gerontol. Geriatr., 1997, 24(3), 233-241.
[] [PMID: 15374110]
Webb, S.J.; Geoghegan, T.E.; Prough, R.A.; Michael Miller, K.K. The biological actions of dehydroepiandrosterone involves multiple receptors. Drug Metab. Rev., 2006, 38(1-2), 89-116.
[] [PMID: 16684650]
Samaras, N.; Samaras, D.; Frangos, E.; Forster, A.; Philippe, J. A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial? Rejuvenation Res., 2013, 16(4), 285-294.
[] [PMID: 23647054]
Kushnir, M.M.; Blamires, T.; Rockwood, A.L.; Roberts, W.L.; Yue, B.; Erdogan, E.; Bunker, A.M.; Meikle, A.W. Liquid chromatography-tandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clin. Chem., 2010, 56(7), 1138-1147.
[] [PMID: 20489135]
Curtis, E.; Litwic, A.; Cooper, C.; Dennison, E. Determinants of muscle and bone aging. J. Cell. Physiol., 2015, 230(11), 2618-2625.
[] [PMID: 25820482]
Raman, M.; Middleton, R.J.; Kalra, P.A.; Green, D. Estimating renal function in old people: an in-depth review. Int. Urol. Nephrol., 2017, 49(11), 1979-1988.
[] [PMID: 28913589]
Baldea, A.J. Effect of aging on renal function plus monitoring and support. Surg. Clin. North Am., 2015, 95(1), 71-83.
[] [PMID: 25459543]
Moman, R.N.; Gupta, N.; Varacallo, M. Physiology, albumin., Available at: https://www.ncbi.nlm.nih. gov/books/NBK459198/#article-17328.s7 (Accessed date: 29 May).
Cabrerizo, S.; Cuadras, D.; Gomez-Busto, F.; Artaza-Artabe, I.; Marín-Ciancas, F.; Malafarina, V. Serum albumin and health in older people: review and meta-analysis. Maturitas, 2015, 81(1), 17-27.
[] [PMID: 25782627]
Gom, I.; Fukushima, H.; Shiraki, M.; Miwa, Y.; Ando, T.; Takai, K.; Moriwaki, H. Relationship between serum albumin level and aging in community-dwelling self-supported elderly population. J. Nutr. Sci. Vitaminol. (Tokyo), 2007, 53(1), 37-42.
[] [PMID: 17484377]
Cooper, J.K.; Gardner, C. Effect of aging on serum albumin. J. Am. Geriatr. Soc., 1989, 37(11), 1039-1042.
[] [PMID: 2809050]
Weaving, G.; Batstone, G.F.; Jones, R.G. Age and sex variation in serum albumin concentration: an observational study. Ann. Clin. Biochem., 2016, 53(Pt 1), 106-111.
[] [PMID: 26071488]
Tiao, J.Y.; Semmens, J.B.; Masarei, J.R.; Lawrence-Brown, M.M. The effect of age on serum creatinine levels in an aging population: relevance to vascular surgery. Cardiovasc. Surg., 2002, 10(5), 445-451.
[] [PMID: 12379401]
Levey, A.S.; Perrone, R.D.; Madias, N.E. Serum creatinine and renal function. Annu. Rev. Med., 1988, 39, 465-490.
[] [PMID: 3285786]
Verma, M.; Khadapkar, R.; Sahu, P.S.; Das, B.R. Comparing age-wise reference intervals for serum creatinine concentration in a “Reality check” of the recommended cut-off. Indian J. Clin. Biochem., 2006, 21(2), 90-94.
[] [PMID: 23105621]
Odden, M.C.; Shlipak, M.G.; Tager, I.B. Serum creatinine and functional limitation in elderly persons. J. Gerontol. A Biol. Sci. Med. Sci., 2009, 64(3), 370-376.
[] [PMID: 19181716]
Vikse, B.E.; Vollset, S.E.; Tell, G.S.; Refsum, H.; Iversen, B.M. Distribution and determinants of serum creatinine in the general population: the Hordaland Health Study. Scand. J. Clin. Lab. Invest., 2004, 64(8), 709-722.
[] [PMID: 15719889]
Maaravi, Y.; Bursztyn, M.; Hammerman-Rozenberg, R.; Cohen, A.; Stessman, J. Moderate renal insufficiency at 70 years predicts mortality. QJM, 2006, 99(2), 97-102.
[] [PMID: 16407374]
Sarnak, M.J.; Katz, R.; Fried, L.F.; Siscovick, D.; Kestenbaum, B.; Seliger, S.; Rifkin, D.; Tracy, R.; Newman, A.B.; Shlipak, M.G.; Cardiovascular Health, S. Cardiovascular Health Study. Cystatin C and aging success. Arch. Intern. Med., 2008, 168(2), 147-153.
[] [PMID: 18227360]
Tanaka, S.; Ando, K.; Kobayashi, K.; Hida, T.; Ito, K.; Tsushima, M.; Morozumi, M.; Machino, M.; Ota, K.; Suzuki, K.; Seki, T.; Ishiguro, N.; Hasegawa, Y.; Imagama, S. Utility of the serum cystatin C level for diagnosis of osteoporosis among middle-aged and elderly people. BioMed Res. Int., 2019, 2019, 5046852.
[] [PMID: 30775381]
Bürkle, A.; Moreno-Villanueva, M.; Bernhard, J.; Blasco, M.; Zondag, G.; Hoeijmakers, J.H.; Toussaint, O.; Grubeck-Loebenstein, B.; Mocchegiani, E.; Collino, S.; Gonos, E.S.; Sikora, E.; Gradinaru, D.; Dollé, M.; Salmon, M.; Kristensen, P.; Griffiths, H.R.; Libert, C.; Grune, T.; Breusing, N.; Simm, A.; Franceschi, C.; Capri, M.; Talbot, D.; Caiafa, P.; Friguet, B.; Slagboom, P.E.; Hervonen, A.; Hurme, M.; Aspinall, R. MARK-AGE biomarkers of ageing. Mech. Ageing Dev., 2015, 151, 2-12.
[] [PMID: 25818235]
Visioli, F.; Hagen, T.M. Nutritional strategies for healthy cardiovascular aging: focus on micronutrients. Pharmacol. Res., 2007, 55(3), 199-206.
[] [PMID: 17317208]
Shlisky, J.; Bloom, D.E.; Beaudreault, A.R.; Tucker, K.L.; Keller, H.H.; Freund-Levi, Y.; Fielding, R.A.; Cheng, F.W.; Jensen, G.L.; Wu, D.; Meydani, S.N. Nutritional considerations for healthy aging and reduction in age-related chronic disease. Adv. Nutr., 2017, 8(1), 17-26.
[] [PMID: 28096124]
Gasmi, A.; Tippairote, T.; Mujawdiya, P.K.; Peana, M.; Menzel, A.; Dadar, M.; Benahmed, A.G.; Bjørklund, G. Micronutrients as immunomodulatory tools for COVID-19 management. Clin. Immunol., 2020, 108545.
[] [PMID: 32710937]
Artaza-Artabe, I.; Sáez-López, P.; Sánchez-Hernández, N.; Fernández-Gutierrez, N.; Malafarina, V. The relationship between nutrition and frailty: Effects of protein intake, nutritional supplementation, vitamin D and exercise on muscle metabolism in the elderly. A systematic review. Maturitas, 2016, 93, 89-99.
[] [PMID: 27125943]
Sprott, R.L. Biomarkers of aging. Exp. Gerontol., 1988, 23(1), 1-3.
[] [PMID: 3384027]
Partridge, L.; Deelen, J.; Slagboom, P.E. Facing up to the global challenges of ageing. Nature, 2018, 561(7721), 45-56.
[] [PMID: 30185958]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy