Balistreri, C.

Carmela Rita Balistreri

Archivio istituzionale della ricerca - Università di Palermo

The current obsession of age-related diseases and the race in identifyingeffective treatments and preventive interventionsCarmela Rita Balistreri*Balistreri CR. The current obsession of age-related diseases and the race inidentifying effective treatments and preventive interventions. J PathobiolPhysiol. December-2017;1(1):2.Today, the phenomenon of ageing characterizes our populations, causing alarge impact in our countries, principally for the growing increase of bothincidence and prevalence of not evolutionally programmed diseases, theage-related diseases (ARDs), including cardiovascular diseases (CVDs),neurodegenerative diseases, metabolic diseases (i.e. insulin resistance,diabetes and metabolic syndrome), and cancer [1]. By 2030,approximately 20% of the population will be aged 65 or older [2]. In thisage group, ARDs, and particularly the CVDs, will result in 40% of alldeaths and rank as the leading cause [3]. On the other hand, the mostimportant determinant of cardiovascular health is person’s age, andprecisely the person biological age, as recently suggested in our studies[4,5]. Accordingly, biological age seems clearly to be a better predictor ofvascular risk rather than chronological age [4,5]. This concept is supportedby key assumptions that peripheral blood leukocyte telomere contentaccurately reflects that of the vascular wall and its decrease is associatedwith premature vascular disease [4,5]. In fact, telomere shortening iscurrently considered the best ageing biomarker, but is also a predictor forARDs, including CVDs [4,5]. A progressive impairment of the cellularprocesses (i.e. mitochondrial dysfunction, telomere attrition, genomicinstability and epigenetic alterations; see Fig.4 of review from Balistreriand co-workers [6]), regulating cardiac and vascular homeostasis,characterizes the vascular ageing, causing as long term effects,endothelium dysfunction, medial degeneration, vascular remodeling anddysfunction [7,8]. They represent pathological entities significantlyassociated with the onset of a large CVD panel, but also of other ARDs.Endothelium dysfunction is the first pathological condition associated notonly with all CVDs, but also with other ARDs, being the endothelial cells(ECs) components of the stroma of all tissues, organs, and the niches ofadult stem cells (ASCs) [9]. This last favors the ASC senescence andincreases their susceptibility to neoplastic transformation and onset ofcancer (i.e. myeloid leukemia), and it temporally reduces their ability toself-repair and regeneration of tissues and organs by facilitating the onsetof degenerative diseases, such as CVDs and neurodegenerative diseases[6,9,10].This current reality of our countries, it is becoming an obsession for bothscientific community and institutions/organizations. The first has focusedits goal in understanding the biology of ageing and ARDs, and to translatethe potential scientific insights obtained into effective interventions, inorder to improve the health in old ages and to retard and/or to delay theonset of ARDs. The second are promoting health promotion’s programs. Inparticular, among the researchers is strong opinion that the solution, tocounteract the ARD onset has the roots in the cellular mechanisms andevolutionally conserved signaling pathways of the cells, as the stem andprogenitor cells (i.e. hematopoietic and no-hematopoietic stem cells andtheir progenitors), involved in the genesis of all tissues, organs andsystems [11]. This is in accordance to the innovative concepts of fetalprogramming-imprinting based on theory popularized, for the first time in1989, by Dr David Barker, and defined as “the fetal origin of adult disease(FOAD)”, as stressed and emphasized in our recent papers, and theemerging concept of maternal imprinting and its influence in fetaldeveloping, programming and fate in adult age [amply quoted in 11reference]. Based on these observations, the field of stem cell biology andevolutionally conserved signaling pathways (i.e. Notch, TLR-4 and others)is becoming the gold object of research of a large number of studies [6,11].Conserved signaling pathways seem to mediate a double role in adulttissues, organs and systems, contributing of their homeostasis, but also theonset of their diseases, such as ARDs. A model has been proposed of ourgroup in recent papers [6,11].Temporally, this growing research in effective therapies and interventionsis becoming a very business for several biotechnological companies,which are promoting a growing number of therapeutic approaches as anti-ageing and anti-ARD treatments, ranging from oxidant drugs, hormones,vitamins and diet supplements to various aesthetic drugs and techniques.In fact, these approaches are particularly costly for gullible patients insearching of well-being and abused by a carefully organized marketinginvolving tacit complicity of doctors, laboratories and companies [12].However, the major number of these treatments until now constitute morea palliative care than a very “long-life elixir”, which has long representedfor humans a dream, a vanity’s sin for remaining young and to longsurvive [12]. This leads to the extemporaneous consideration that the wayfor developing effective anti-ageing and anti-inflamm-ageing treatments inhumans is distant. Despite this, there is among the ageing’s researchers theoptimistic hope in identifying successful treatments and approaches forhumans too. It derives from the increase of lifespan observed in short-livedmodel organisms (i.e. yeast, worm, fillies, mice and rats) undergone tovarious genetic, dietary, and pharmacological interventions [12]. Inaddition, some of these treatments have also demonstrated to retard theonset of ARDs and consequently to extend the health-span (i.e. the lengthof time one lives in good health), as evidenced in 2014 by Kennedy andco-workers [13]. Thus, it is possible to affirm that this evidence in animalmodels leads to the promise to develop effective life-extendinginterventions in humans too. Recently, different approaches are emergingranging from pharmacological targeting of ageing, basic biological assays,big data analysis to the recent use of young blood, metformin andmelatonin treatments, nutritional approaches, stem cells, cellular, geneticand epigenetic reprogramming or other techniques of regenerativemedicine. Thus, a large number of potential anti-ageing interventionscurrently exist, but only a little fraction has the features for its testing inclinical applications [14].In addition, it is emerging the necessity to developing different treatmentsor interventions for male and female individuals in old age, andparticularly for female subjects. For example, accruing evidence indicatesthat women and men experience the diabetes and CVDs differently and itEDITORIAL ARTICLEDepartment of Pathobiology and Medical and Forensic Biotechnologies, University of Palermo, Palermo, Italy*Correspondence: Carmela R. Balistreri, Department of Pathobiology and Medical Biotechnologies, University of Palermo, Corso Tukory 211, Palermo,90134 Italy, Fax: +390916555933, E-mail: carmelarita.balistreri@unipa.itReceived: 04 October 2017, Accepted: 25 October 2017, Published: 31 October 2017This open-access article is distributed under the terms of the Creative Commons Attribution Non-Commercial License (CC BY-NC) (http://creativecommons.org/licenses/by-nc/4.0/), which permits reuse, distribution and reproduction of the article, provided that the original work isproperly cited and the reuse is restricted to noncommercial purposes. For commercial reuse, contact reprints@pulsus.comJ Pathobiol Physiol Vol.1 No.1 December-2017 1has been also observed that the relative risk for fatal ischemic heart diseaseassociated with diabetes is 50% higher in women than in men [15]. Thus,sex dimorphism determines a complex pathological picture in onset of theseARDs, and in women it is exacerbated by the complex interaction amonggenetic, hormonal and environmental factors, as described in 2005 byMendelsohn and Karas in Science journal [16] and stressed in our paper[15]. Regarding the role of genetic factors, studies on sex chromosomes,their gene content and the related disease risk are emerging. Wiham and co-workers are recently summarized some new literature data and stressed thatCVDs, as well as diabetes, represent complex genetic traits with phenotypesinfluenced by genetic, hormonal, environmental, and cultural variables [17].Thus sex differences must be considered in the future investigations and thedevelopment of effective therapies and preventive approaches.We recently suggested that each individual is the result of the sophisticatedinterplay between environmental factors and its genome, trascriptome,proteome, metabolome, microbiome, epigenome, exposome [6,18]. Thus, itis necessary to perform a more complex combination of investigationsbased on genetic, transcriptomic, proteomic, metabolomic, microbiomicand epigenetic evaluations, for obtaining interesting data in the study ofthese diseases. In addition, computational investigations are alsorecommended, as well as collecting environmental and biometric data,medical/scientific/health care records [6,18]. Thus, we have proposed thatthe integration of all data, obtained in this large panel of investigations, andtheir elaboration might lead to the development of appropriate agonists,antagonists, inhibitors of specific signaling disease pathways, which mightbe used in a near future as personalized treatments for these diseases,facilitating their management and outcome [6,18]. Thus, the solution mightbe in looking with new eyes the goal of ageing and ARD research in orderto make new discoveries, although, the ways to execute still are long anddifficult [18].References1. Sims J. Our ageing population: Insights from the 2016 Census. Australas JAgeing. 2017;36:176.2. Edwards RD. Population aging the dependency burden, and challengesfacing preventive medicine. Prev Med. 2012;55:533-4.3. Heidenreich PA, Trogdon JG, Khavjou OA, et al. Forecasting the future ofcardiovascular disease in the United States: a policy statement from theAmerican Heart Association. Circulation. 2011;123:933-44.4. Balistreri CR, Pisano C, Merlo D, et al. Is the mean blood leukocytetelomere length a predictor for sporadic thoracic aortic aneurysm? Datafrom a preliminary study. Rejuvenation Res. 2012;15:170-3.5. Balistreri CR, Pisano C, Martorana A, et al. Are the leukocyte telomerelength attrition and telomerase activity alteration potential predictorbiomarkers for sporadic TAA in aged individuals? Age (Dordr).2014;36:9700.6. Balistreri CR, Ruvolo G, Lio D, et al.Toll-like receptor-4 signaling pathwayin aorta aging and diseases: "its double nature". J Mol Cell Cardiol.2017;110:38-53.7. Regina C, Panatta E, Candi E, et al. Vascular ageing and endothelial cellsenescence: Molecular mechanisms of physiology and diseases. MechAgeing Dev. 2016;159:14-21.8. Madonna R, Novo G, Balistreri CR. Cellular and molecular basis of theimbalance between vascular damage and repair in ageing and age-relateddiseases: As biomarkers and targets for new treatments. Mech Ageing Dev.2016;159:22-30.9. Olivieri F, Pompilio G, Balistreri CR. Endothelial progenitor cells in ageing.Mech Ageing Dev. 2016;159:1-3.10. Nasello M, Schirò G, Crapanzano F, et al. Stem Cells and Other EmergingAgents as Innovative "Drugs" in Neurodegenerative Diseases: Benefits andLimitations. Rejuvenation Res. 2017.11. Balistreri CR, Madonna R, Melino G, et al. The emerging role of Notchpathway in ageing: Focus on the related mechanisms in age-related diseases.Ageing Res Rev. 2016;29:50-65.12. de Magalhães JP, Stevens M, Thornton D. The Business of Anti-AgingScience. Trends Biotechnol. 2017;S0167-7799:30171-3.13. Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging tochronic disease. Cell. 2014;159:709-13.14. Balistreri CR. Anti-inflamm-ageing and/or anti-age-related diseaseemerging treatments: a historical alchemy or revolutionary effectiveprocedures? Mediators Inflamm. 2017.15. Madonna R, Balistreri CR, De Rosa S, Selvaggio S, Selvaggio, De CaterinaR. Gender differences in coronary artery disease and diabetes. Int. J.Cardiol. 2017.16. Mendelsohn ME, Karas RH. Molecular and cellular basis of cardiovasculargender differences. Science. 2005;308:1583-7.17. Winham SJ, de Andrade M, Miller VM. Genetics of cardiovascular disease:Importance of sex and ethnicity. Atherosclerosis. 2015;241:219-28.18. Balistreri CR.“Endothelial progenitor cells: a new real hope or only anunrealizable dream?” Springer International Publishing, Dordrecht.2017;1-80. Balistreri CR2 J Pathobiol Physiol Vol.1 No.1 December-2017

The current obsession of age-related diseases and the race in identifying
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The current obsession of age-related diseases and the race in identifying effective treatments and preventive interventions

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