[Frontiers in Bioscience, Landmark, 22, 982-990, January 1, 2017]

Third phase science: defining a novel model of research into human ageing

Marios Kyriazis 1

1ELPIs Foundation for Indefinite Lifespans, York Road, London TW106DR

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Discussion
    3.1. The three phases of scientific inquiry
    3.2. The patient in the context of the environment
    3.3. Item-based, physical therapies
4. The alternative model
5. Conclusion
6. Acknowledgement
7. References

1. ABSTRACT

While the current paradigm of research into ageing relies heavily upon reductionist premises, and it has clearly not produced any of the dramatic benefits anticipated in our fight against ageing, the majority of scientists are hesitant, unable or unwilling to consider different or alternative models. In this paper I will discuss some of the shortcomings of a reductionist view of research aimed at finding treatments against ageing degeneration, and I will highlight several areas where proposed future treatments for basic age-relateddegeneration may be vulnerable to severe criticism. As an alternative model, I will attempt to present a different integrative concept of research which may result in a decrease of the impact of ageing, in participating humans. This model is based on a more inclusive worldview, examining the relationship between humans and their environment, the integration of humans with technology, and the biological consequences of an increasingly techno-cognitive ecosystem.

7. REFERENCES

1. I Stambler: A History of Life-Extensionism in the Twentieth Century, Rison Lezion, Israel (2014)

2. AD de Grey: Rejuvenation Biotechnology: The Industry Emerges, but Short-Termism Looms. Rejuvenation Res 19(3), 193-4 (2016)
DOI: 10.1089/rej.2016.1846

3. IM Conboy, MJ Conboy, J Rebo: Systemic Problems: A perspective on stem cell aging and rejuvenation. Aging (Albany NY) 7(10),754-65 (2015)
DOI: 10.18632/aging.100819

4. Y Zhu, T Tchkonia, T Pirtskhalava: The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell 14(4), 644-58 (2015)
DOI: 10.1111/acel.12344

5. DM Huffman, MJ Schafer, NK LeBrasseur: Energetic interventions for healthspan and resiliency with aging. Exp Gerontol. pii: S0531-5565(16)30147-4 (2016)
(doi not found)

6. L Demontis: Comparative Analysis of Medieval and Modern Scientific Research on Ageing Reveals Many Conceptual Similarities. Gerontol & Ger Res 4/3: 216, 1-4 (2015)
DOI: 10.4172/2167-7182.1000216

7. M Kyriazis, A Apostolides: The Fallacy of the Longevity Elixir: Negligible Senescence May be Achieved, but Not by Using Something Physical. Curr Aging Sci 8(3), 227-34 (2015)
DOI: 10.2174/1874609808666150702095803

8. M Kyriazis: The impracticality of biomedical rejuvenation therapies: translational and pharmacological barriers. Rejuvenation Res 17(4), 390-6 (2014)
DOI: 10.1089/rej.2014.1588

9. BA Carnes, SJ Olshansky, L Hayflick L: Can human biology allow most of us to become centenarians? J Gerontol A Biol Sci Med Sci 68(2), 136-42 (2013)
DOI: 10.1093/gerona/gls142

10. KC Bausch: The Theory and Practice of Third Phase Science, Social Systems and Design. Transl Sys Sci 1, 129-145 (2014)
(doi not found)

11. R Harre: Cognitive Science: A Philosophical Introduction, Sage Publications London (2002)

12. AM Hall, PH Ferreira, CG Maher, J Latimer, ML Ferreira: The Influence of the Therapist-Patient Relationship on Treatment Outcome in Physical Rehabilitation. Phys Ther, 90, 1099-1110 (2010)
DOI: 10.2522/ptj.20090245

13. C Gershenson, N Fernández: Complexity and information: Measuring emergence, self-organization, and homeostasis at multiple scales. Complexity 18(2), 29-44 (2012)
DOI: 10.1002/cplx.21424

14. GS Metcalf (Ed). Social Systems and Design. Springer Ashland USA (2014)

15. G de Zeeuw: Three phases of science: A methodological exploration. Working paper nr. 7 of the Centre for Systems and Information Sciences, University of Humberside, ISBN 1 86050 025. (1996) http://www.cict.demon.co.uk/Threephases01.PDF
(doi not found)

16. KC Bausch, TR Flanagan: A Confluence of Third Phase Science And Dialogic Design Science (2012) https://www.gwu.edu/~uscs/docs/1112/ThirdPhaseScienceandDDS%20JRP.doc
(doi not found)

17. EA Necka, S Cacioppo, JT Cacioppo: Social Neuroscience of the Twenty-First Century. The University of Chicago, Chicago, IL, USA (2015)
DOI: 10.1016/b978-0-08-097086-8.56020-6

18. JT Cacioppo, GG Berntson: Social psychological contributions to the decade of the brain: doctrine of multilevel analysis. American Psychologist 47, 1019-1028 (1992)
DOI: 10.1037/0003-066X.47.8.1019

19. SN Haber, PR Barchas. The regulatory effect of social rank on behavior after amphetamine administration. In: Social Hierarchies: Essays toward a Socio-physiological Perspective. Ed: PR Barchas, pp119–132. Greenwood, Westport, CT (1983)

20. M Kyriazis: Opinion Paper: A Cognitive-cultural Segregation and the Three Stages of Aging. Curr Aging Sci 9, 81-6 (2016)
DOI: 10.2174/1874609809666151214104202

21. SW Cole: Social Regulation of Human Gene Expression: Mechanisms and Implications for Public Health. Am J Public Health 103 (S1), S84–S92 (2013)
DOI: 10.2105/AJPH.2012.301183

22. J Guerin: Emerging area of aging research: long-lived animals with “negligible senescence. Ann N Y Acad Sci 1019, 518-20 (2004)
DOI: 10.1196/annals.1297.096

23. SI Arriola Apelo, DW Lamming: An InhibiTOR of Aging Emerges From the Soil of Easter Island. J Gerontol A Biol Sci Med Sci 71(7), 841-9 (2016)
DOI: 10.1093/gerona/glw090

24. N Barzilai, JP Crandall, SB Kritchevsky, MA Espeland: Metformin as a Tool to Target Aging. Cell Meta, 23(6), 1060-5 (2016)
DOI: 10.1016/j.cmet.2016.05.011

25. A Camins, FX Sureda, F. Junyent, E Verdaguer, J Folch, C Pelegri, J Vilaplana, C Beas-Zarate, M Pallàs: Sirtuin activators: designing molecules to extend life span. Biochim Biophys Acta 1799(10-12),740-9 (2010)
DOI: 10.1016/j.bbagrm.2010.06.005

26. NK Choudhry, MA Fischer, J Avorn, JN Liberman, S Schneeweiss, J Pakes, TA Brennan, WH Shrank: The implications of therapeutic complexity on adherence to cardiovascular medications. Arch Intern Med 171, 814-822 (2011)
DOI: 10.1001/archinternmed.2010.495
DOI: 10.1001/archinternmed.2011.176

27. 27. WF Gellad, K Grenard, EA McGlynn: A review of barriers to medication adherence: a framework for driving policy options. RAND (2009). http://www.rand.org/content/dam/rand/pubs/technical_reports/2009/RAND_TR765.pdf (Retrieved September 4, 2016)
(doi not found)

28. CA Jackevicius, P Li, JV Tu: Prevalence, predictors, and outcomes of primary non-adherence after acute myocardial infarction. Circulation 117, 1028-1036 (2008)
DOI: 10.1161/CIRCULATIONAHA.107.706820

29. N Singh, C Squier, C Sivek, M Wagener, MH Nguyen, VL Yu: Determinants of compliance with antiretroviral therapy in patients with human immunodeficiency virus: prospective assessment with implications for enhancing compliance. AIDS Care 8(3), 261-9 (1996)
DOI: 10.1080/09540129650125696

30. F Puigventós, M Riera, C Delibes, M Peñaranda, L de la Fuente, A Boronat: Adherence to antiretroviral drug therapy. A systematic review. Med Clin (Barc) 119(4), 130-7 (2002)
DOI: 10.1016/S0025-7753(02)73341-1

31. RH Chapman, JS Benner, AA Petrilla, JC Tierce, SR Collins, DS Battleman, JS Schwartz: Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch Intern Med 163, 1147-1152 (2005)
DOI: 10.1001/archinte.165.10.1147

32. AJ Claxton, J Cramer, C Pierce: A systematic review of the associations between dose regimens and medication compliance. Clin Ther 23, 1296-1310 (2012)
DOI: 10.1016/S0149-2918(01)80109-0

33. I Barat, F Andreasen, EMS Damsgaard: Drug therapy in the elderly: what doctors believe and patients actually do. Br J Clin Pharmacol 51(6), 615–622 (2001)
DOI: 10.1046/j.0306-5251.2001.01401.x

34. EJ Lenze, MD Miller, MA Dew, LM Martire, BH Mulsant, AE Begley, R Schulz, E Frank, CF Reynolds: Subjective health measures and acute treatment outcomes in geriatric depression. Int J Geriatr Psychiatry 16(12), 1149-55 (2001)
DOI: 10.1002/gps.503

35. EM Donadiki, R Jiménez-García, V Hernández-Barrera, P Sourtzi, P Carrasco-Garrido, A López de Andrés, I Jimenez-Trujillo, EG Velonakis: Health Belief Model applied to non-compliance with HPV vaccine among female university students. Public Health 128(3), 268-73 (2014)
DOI: 10.1016/j.puhe.2013.12.004

36. S Malhotra, RS Karan, P Pandhi, S Jain: Drug related medical emergencies in the elderly: role of adverse drug reactions and non-compliance. Postgrad Med J 77(913), 703-7 (2001)
DOI: 10.1136/pmj.77.913.703

37. JG Shepherd, E Locke, Q Zhang, G Maihafer: Health services use and prescription access among uninsured patients managing chronic diseases. J Community Health 39(3), 572-83 (2014)
DOI: 10.1007/s10900-013-9799-1

38. GM Cochrane, R Horne, P Chanez: Compliance in asthma. Respir Med 93(11),763-9 (1999)
DOI: 10.1016/S0954-6111(99)90260-3

39. DT Campbell: Downward Causation in Hierarchically Organised Biological Systems. In Studies in the Philosophy of Biology. Eds: FJ Ayala, T Dobzhansky Macmillan Publishers London, 179-186 (1974)
DOI: 10.1007/978-1-349-01892-5_11

40. MR Stratton, PJ Campbell, PA Futreal. The cancer genome. Nature 458(7239), 719-24 (2009)
DOI: 10.1038/nature07943

41. S Ogino, R Nishihara, TJ VanderWeele, M Wang, A Nishi, P Lochhead, ZR Qian, X Zhang, K Wu, H Nan, K Yoshida, DA Milner, AT Chan, AE Field, CA Camargo, MA Williams, EL Giovannucci: Review Article: The Role of Molecular Pathological Epidemiology in the Study of Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine. Epidemiology 27(4), 602-11 (2016)
DOI: 10.1097/EDE.0000000000000471

42. A Nishi, DA Milner, EL Giovannucci, R Nishihara, AS Tan, I Kawachi, S Ogino: Integration of molecular pathology, epidemiology and social science for global precision medicine. Expert Rev Mol Diagn 16(1), 11-23 (2016)
DOI: 10.1586/14737159.2016.1115346

43. C Bell, R McWilliam, A Purvis, A Tiwari: Concepts of self-repairing systems. Measurement and Control 46(6), 176-179 (2013)
DOI: 10.1177/0020294013492285

44. A Christakis, Y Laouris: Harnessing the wisdom of the people. The tree of social action. Proceedings of the 3rd international conference of the Hellenic Society of systems sciences, Pireus, 26-28 May, (2007)
(doi not found)

45. Y Laouris, R Laouri, A Christakis: Communication Praxis for Ethical Accountability: The Ethics of the Tree of Action: Dialogue and Breaking down the Wall in Cyprus. Sys Res Behavioral Sci 25, 1-16 (2008)
DOI: 10.1002/sres.890

46. A Goldman: Ray Kurzweil says we’re going to live forever. New York Times Magazine. 25 January 2013. http://www.nytimes.com/2013/01/27/magazine/ray-kurzweil-says-were-going-to-live-forever.html?_r=0 (accessed 31 August 2016)
(doi not found)

47. http://www.bbc.co.uk/programmes/p0211msj

48. M Bergen: What’s He Building in There? The Stealth Attempt to Defeat Aging at Google’s Calico. Recode, (2015) http://www.recode.net/2015/12/28/11621734/the-stealth-attempt-to-defeat-aging-at-googles-calico (accessed 31 August 2016)

49. http://www.sens.org

50. M Kyriazis: Editorial: Novel approaches to an old problem: insights, theory and practice for eliminating aging. Curr Aging Sci 4;7 (1), 1-2 (2014)
(doi not found)

51. D Helbing: FuturICT-New science and technology to manage our complex, strongly connected world (2011). http://arxiv.org/abs/1108.6.131 (accessed 26 August 2016)
(doi not found)

52. M Kyriazis: Systems neuroscience in focus: from the human brain to the global brain? Front. Syst. Neurosci 9,7 (2015)
DOI: 10.3389/fnsys.2015.00007

53. M Kyriazis: Information-sharing, adaptive epigenetics and human longevity. http://arxiv.org/abs/1407.6.030 (2014) (accessed 20 August 2016)
(doi not found)

54. M Kyriazis. Reversal of informational entropy and the acquisition of germ-like immortality by somatic cells. Curr Aging Sci 7(1), 9-16 (2014)
DOI: 10.2174/1874609807666140521101102

55. MW Feldman. KN Laland: Gene-culture coevolutionary theory. Trends Ecol Evol 11, 453-7 (1996)
DOI: 10.1016/0169-5347(96)10052-5

56. M Chudek, J Henrich: Culture-gene coevolution, norm-psychology and the emergence of human prosociality. Trends Cogn Sci 15(5), 218-26 (2011)
DOI: 10.1016/j.tics.2011.03.003

57. M Kyriazis: Technological integration and hyper-connectivity: Tools for promoting extreme human lifespans. Complexity 20, 5-24 (2014)
(doi not found)

58. M Kyriazis: Clinical Effects of a ‘Human-Computer’ Interaction. SSRN, June 21 (2016). http://ssrn.com/abstract=2798529
(doi not found)

59. M Levi-Ferber, H Gian, R Dudkevich, S Henis-Korenblit: Transdifferentiation mediated tumor suppression by the endoplasmic reticulum stress sensor IRE-1 in C. elegans. Elife. Jul 20, 4 (2015)
(doi not found)

60. R Chavez-Valdez, DL Flock, LJ Martin, FJ Northington: Endoplasmic reticulum pathology and stress response in neurons precede programmed necrosis after neonatal hypoxia-ischemia. Int J Dev Neurosci 48, 58-70 (2016)
DOI: 10.1016/j.ijdevneu.2015.11.007

61. A Yoshikawa, T Kamide, K Hashida, HM Ta, Y Inahata, M Takarada-Iemata, T Hattori, K Mori, R Takahashi, T Matsuyama, Y Hayashi, Y Kitao, O Hori: Deletion of Atf6α impairs astroglial activation and enhances neuronal death following brain ischemia in mice. J Neurochem 132(3), 342-53 (2015)
DOI: 10.1111/jnc.12981

62. JJ Riches, K Reynolds: Jnk1 activity is indispensable for appropriate cortical interneuron migration in the developing cerebral cortex. J Neurosci 34(43), 14165-6 (2014)
DOI: 10.1523/JNEUROSCI.3222-14.2014

63. L Seifert, J Komar, D Araujo, K Davids: Neurobiological degeneracy: A key property for functional adaptations of perception and action to constraints. Neurosci Biobehav Rev Aug 6, S0149-7634(16)30348-7 (2016)
(doi not found)

64. GV Glinsky: Mechanistically distinct pathways of divergent regulatory DNA creation contribute to evolution of human-specific genomic regulatory networks driving phenotypic divergence of Homo sapiens. Genome Biol Evol Aug 8. pii: evw185. (Epub ahead of print) (2016)
(doi not found)

65. FS de Souza, LF Franchini, M Rubinstein: Exaptation of transposable elements into novel cis-regulatory elements: is the evidence always strong? Mol Biol Evo 30(6), 1239-51 (2013)
DOI: 10.1093/molbev/mst045

66. B Pfeuty, Q Thommen: Adaptive Benefits of Storage Strategy and Dual AMPK/TOR Signaling in Metabolic Stress Response. PLoS One 11(8), e0160247 (2016)
DOI: 10.1371/journal.pone.0160247

67. V Tosato, J Sims, N West, M Colombin, CV Bruschi: Post-translocational adaptation drives evolution through genetic selection and transcriptional shift in Saccharomyces cerevisiae. Curr Genet Aug 4. (Epub ahead of print)) (2016)
(doi not found)

68. M Kyriazis: The Indispensable Soma Hypothesis. (2016) https://figshare.com/articles/New_draft_item_The_Indispensable_Soma_Hypothesis/3079732
(doi not found)

69. M Kyriazis (ed). Re-thinking ageing: a cross-disciplinary perspective (Special issue). Mech Ageing Dev (2017) (in press)
(doi not found)

Key Words: Ageing, Degeneration, Third Phase Science, Reductionism, Rejuvenation, Biotechnologies, Techno-Culture, Review

Send correspondence to: Marios Kyriazis, ELPIs Foundation for Indefinite Lifespans, York Road, London TW106DR, UK, Tel: 00447850221796. E-mail: drmarios@live.it