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Aging and Disease    2014, Vol. 5 Issue (3) : 196-202     DOI: 10.14336/AD.2014.0500196
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Aging Is Not a Disease: Implications for Intervention
Suresh I. S. Rattan
Laboratory of Cellular Ageing, Department of Molecular Biology and Genetics, Aarhus University, Denmark
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Abstract  

Aging of biological systems occurs in spite of numerous complex pathways of maintenance, repair and defense. There are no gerontogenes which have the specific evolutionary function to cause aging. Although aging is the common cause of all age-related diseases, aging in itself cannot be considered a disease. This understanding of aging as a process should transform our approach towards interventions from developing illusory anti-aging treatments to developing realistic and practical methods for maintaining health throughout the lifespan. The concept of homeodynamic space can be a useful one in order to identify a set of measurable, evidence-based and demonstratable parameters of health, robustness and resilience. Age-induced health problems, for which there are no other clear-cut causative agents, may be better tackled by focusing on health mechanisms and their maintenance, rather than only disease management and treatment. Continuing the disease-oriented research and treatment approaches, as opposed to health-oriented and preventive strategies, are economically, socially and psychologically unsustainable.

Keywords longevity      stress      homeostasis      homeodynamics      hormetics      hormesis      hormetin     
Corresponding Authors: Suresh I. S. Rattan   
Issue Date: 04 November 2014
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Suresh I. S. Rattan. Aging Is Not a Disease: Implications for Intervention[J]. Aging and Disease, 2014, 5(3): 196-202.
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http://www.aginganddisease.org/EN/10.14336/AD.2014.0500196     OR     http://www.aginganddisease.org/EN/Y2014/V5/I3/196
Biological processMolecular mediators
Sensing and responding to intra- and extracellular stressReceptors and signaling molecules, stress-responding transcription factors, chaperones, anti-oxidative enzymes, cytokines, sirtuins
Nuclear and mitochondrial DNA repairDNA repair systems
Protein repair and degradation.Proteasome, protein repair systems
Removal and turnover of defective macromolecules and organellesAutophagosomes, lysosomes
Defences against reactive oxygen species and other free radicalsAntioxidants, antioxidative enzymes
Detoxification of chemicals and nutritional metabolitesCytchrome P450, phase-I and phase-II enzymes
Innate and adaptive immune responses and apoptosisCaspases, cytokines, antibodies
Wound healing, tissue regeneration and other higher order processes, including thermal regulation, neuro-endocrine balance, daily rhythmsCytokines, growth factors, signaling molecules
Table 1.  Biological maintenance and repair systems and their molecular mediators for longevity assurance and essential lifespan(modified from [23])
[1] Holliday R(2006). Aging is no longer an unsolved problem in biology. Ann NY Acad Sci, 1067:1-9
http://dx.doi.org/10.1196/annals.1354.002
[2] Hayflick L(2007). Biological aging is no longer an unsolved problem. Ann NY Acad Sci, 1100:1-13
http://dx.doi.org/10.1196/annals.1395.001
[3] Rattan SIS(2000). Biogerontology: the next step. Ann NY Acad Sci, 908:282-290
[4] Rattan SIS(2006). Theories of biological aging: genes, proteins and free radicals. Free Rad Res, 40:1230-1238
http://dx.doi.org/10.1080/10715760600911303
[5] Carnes BA(2007). Senescence viewed through the lens of comparative biology. Ann N Y Acad Sci, 1114:14-22
http://dx.doi.org/10.1196/annals.1396.045
[6] Carnes BA(2011). What is lifespan regulation and why does it exist?. Biogerontology, 12:367-374
http://118.145.16.217/magsci/article/article?id=15697485
[7] Carnes BA, Olshansky SJ, Grahn D(2003). Biological evidence for limits to the duration of life. Biogerontology, 4:31-45
http://118.145.16.217/magsci/article/article?id=15774871
[8] Mentis AF, Kararizou E(2010). Does ageing originate in utero?. Biogerontology, 11:725-729
http://118.145.16.217/magsci/article/article?id=15575239
[9] Gavrilov LA, Gavrilova NS(2011). Mortality Measurement at Advanced Ages: A Study of the Social Security Administration Death Master File. N Am Actuar J, 15:432-447
http://dx.doi.org/10.1080/10920277.2011.10597629
[10] Gavrilov LA, Gavrilova NS(2012). Biodemography of exceptional longevity: early-life and mid-life predictors of human longevity. Biodemography Soc Biol, 58:14-39
http://dx.doi.org/10.1080/19485565.2012.666121
[11] Carnes BA, Witten TM(2013). How long must humans live?. J Gerontol Bio Sciin press
doi: 10.1093/gerona/glt164
[12] Hayflick L(2007). Entropy explains aging, genetic determinism explains longevity, and undefined terminology explains misunderstanding both. PLoS Genet, 3:e220
http://dx.doi.org/10.1371/journal.pgen.0030220
[13] Holliday R(2009). Genes and the evolution of longevities. Biogerontology, 10:1-2
http://118.145.16.217/magsci/article/article?id=17210594
[14] Holliday R, Rattan SIS(2010). Longevity mutants do not establish any “new science” of ageing. Biogerontology, 11:507-511
http://118.145.16.217/magsci/article/article?id=15573859
[15] Demetrius L(2013). Boltzmann, Darwin and directionality theory. Physics Reports, 530:1-85
http://dx.doi.org/10.1016/j.physrep.2013.04.001
[16] Gavrilov LA, Gavrilova NS(2001). The reliability theory of aging and longevity. J Theor Biol, 213:527-545
http://dx.doi.org/10.1006/jtbi.2001.2430
[17] Gladyshev VN(2013). The origin of aging: imperfectness-driven non-random damage defines the aging process and control of lifespan. Trends Genet, 29:506-512
http://dx.doi.org/10.1016/j.tig.2013.05.004
[18] Holliday R(2007). Ageing: the paradox of lifeDordrecht, The NetherlandsSpringer
[19] Kirkwood TBL Time of Our LivesLondonWeidenfeld & Nicolson1999
[20] Wensink M(2013). Age-specificity and the evolution of senescence: a discussion. Biogerontology, 14:99-105
http://dx.doi.org/10.1007/s10522-012-9410-7
[21] Wensink MJ, van Heemst D, Rozing MP, Westendorp RG(2012). The maintenance gap: a new theoretical perspective on the evolution of aging. Biogerontology, 13:197-201
http://118.145.16.217/magsci/article/article?id=17528232
[22] Martin GM(2007). Modalities of gene action predicted by the classical evolutionary theory of aging. Ann NY Acad Sci, 1100:14-20
http://dx.doi.org/10.1196/annals.1395.002
[23] Rattan SIS(2008). Increased molecular damage and heterogeneity as the basis of aging. Biol Chem, 389:267-272
[24] Yates FE(1994). Order and complexity in dynamical systems: homeodynamics as a generalized mechanics for biology. Math Comput Model, 19:49-74
[25] Demirovic D, Rattan SIS(2013). Establishing cellular stress response profiles as biomarkers of homeodynamics, health and hormesis. Exp Gerontol, 48:94-98
http://118.145.16.217/magsci/article/article?id=19847070
[26] Rattan SIS(2010). Taregeting the age-related occurrence, removal, and accumulation of molecular damage by hormesis. Ann N Y Acad Sci, 1197:28-32
http://dx.doi.org/10.1111/j.1749-6632.2010.05193.x
[27] Rattan SIS(2012). Biogerontology: from here to where? The Lord Cohen Medal Lecture-2011. Biogerontology, 13:83-91
http://118.145.16.217/magsci/article/article?id=17460150
[28] Rattan SIS(2013). Healthy ageing, but what is health?. Biogerontologyin press
doi: 10.1007/s10522-013-9442-7
[29] Rattan SIS, Demirovic D(2009). Hormesis and aging. Mattson MP, Calabrese E Hormesis: a revolution in biology, toxicology and medicineNew YorkSpringer153-175
[30] Rattan SIS(2007). Homeostasis, homeodynamics, and aging. Birren J Encyclopedia of GerontologyUKElsevier Inc696-699
[31] Rattan SIS(1995). Gerontogenes: real or virtual?. FASEB J, 9:284-286
[32] Blagosklonny MV(2012). Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging. Aging (Albany NY)4:159-165
[33] Demetrius L(2004). Calorie restricition, metabolic rate and entropy. J Gerontol Biol Sci, 59A:902-915
[34] Le Bourg E(2000). Gerontologists and the media: false hopes and fantasies can be hazardous for science. Biogerontology, 1:371-372
http://118.145.16.217/magsci/article/article?id=16034463
[35] Le Bourg E(2013). Obsolete ideas and logical confusions can be obstacles for biogerontology research. Biogerontology, 14:221-227
http://dx.doi.org/10.1007/s10522-013-9418-7
[36] Olshansky SJ, Carnes BA(2012). Science fact versus SENS foreseeable. Gerontology, 59:190-192
[37] Warner H, Anderson J, Austad S, Bergamini E, Bredesen D, Butler R(2005). Science fact and the SENS agenda. What can we reasonably expect from ageing research?. EMBO Rep, 6:1006-8
http://dx.doi.org/10.1038/sj.embor.7400555
[38] O’Neill D(2013). 2012 - That was the year that was. Age Ageing
[39] Tacutu R, Budovsky A, Yanai H, Fraifeld VE(2011). Molecular links between cellular senescence, longevity and age-related diseases - a systems biology perspective. Aging (Albany NY)3:1178-1191
[40] Walter S, Atzmon G, Demerath EW, Garcia ME, Kaplan RC, Kumari M(2011). A genome-wide association study of aging. Neurobiol Aging, 32:2109 e15-28
http://dx.doi.org/10.1016/j.neurobiolaging.2011.05.026
[41] Watson J(2013). Oxidants, antioxidants and the current incurability of metastatic cancers. Open Biol, 3:120144
http://dx.doi.org/10.1098/rsob.120144
[42] Farrelly C(2008). A tale of two strategies. EMBO Rep, 9:92-95
[43] Olshansky SJ, Biggs S, Achenbaum WA, Davison GC, Fried L, Gutman G(2011). The global agenda council on the ageing society: policy principles. Global Policy, 2:97-105
http://dx.doi.org/10.1111/j.1758-5899.2010.00053.x
[44] Vaupel JW(2010). Biodemography of human ageing. Nature, 464:536-542
http://dx.doi.org/10.1038/nature08984
[45] Carnes BA, Olshansky SJ, Hayflick L(2012). Can Human Biology Allow Most of Us to Become Centenarians?. J Gerontol A Biol Sci Med Sci
[46] Goldman DP, Cutler D, Rowe JW, Michaud PC, Sullivan J, Peneva D(2013). Substantial health and economic returns from delyaed aging may warrant a new focus for medical research. Health Aff (Millwood)32:1698-1705
http://dx.doi.org/10.1377/hlthaff.2013.0052
[47] Fulop T, Larbi A, Witkowski JM, McElhaney J, Loeb M, Mitnitski A(2010). Aging, frailty and age-related diseases. Biogerontology, 11:547-563
http://118.145.16.217/magsci/article/article?id=15574272
[48] Hubbard RE, Woodhouse KW(2010). Frailty, inflammation and the elderly. Biogerontology, 11:635-641
http://118.145.16.217/magsci/article/article?id=15574361
[49] Mitnitski A, Song X, Rockwood K(2013). Assessing biological aging: the origin of deficit accumulation. Biogerontology, 14in press.
[50] Montesanto A, Lagani V, Martino C, Dato S, De Rango F, Berardelli M(2010). A novel, population-specific approach to define frailty. Age, 32:385-395
http://118.145.16.217/magsci/article/article?id=16352111
[51] Engberg H, Christensen K, Andersen-Ranberg K, Vaupel JW, Jeune B(2008). Improving activities of daily living in danish centenarians--but only in women: a comparative study of two birth cohorts born in 1895 and 1905. J Gerontol A Biol Sci Med Sci, 63:1186-1192
http://dx.doi.org/10.1093/gerona/63.11.1186
[52] Huber M, Knottnerus JA, Green L, van der Horst H, Jadad AR, Kromhout D(2011). How should we define health?. BMJ, 343:d4163
http://dx.doi.org/10.1136/bmj.d4163
[53] Franco OH, Karnik K, Osborne G, Ordovas JM, Catt M, van der Ouderaa F(2009). Changing course in ageing research: The healthy ageing phenotype. Maturitas, 63:13-19
http://118.145.16.217/magsci/article/article?id=15244399
[54] Richter J, Schwarz M, Bauer B(2008). Personality characteristics determine health-related quality of life as an outcome indicator of geriatric inpatient rehabilitation. Curr Gerontol Geriatr ResArticle ID 474618
doi: 10.1155/2008/474618:8
[55] Steptoe A, Leigh ES, Kumari M(2011). Positive affect and distressed affect over the day in older people. Psychol Aging, 26:956-965
http://dx.doi.org/10.1037/a0023303
[56] Byerley LO, Leamy L, Tam SW, Chou CW, Ravussin E(2010). Development of a serum profile for healthy aging. Age, 32:497-507
http://118.145.16.217/magsci/article/article?id=16352590
[57] Kitano H(2007). Towards a theory of biological robustness. Mol Syst Biol, 3:137
[58] Kriete A(2013). Robustness and aging- a systems-level perspective. Biosystems, 112:37-48
http://118.145.16.217/magsci/article/article?id=19610257
[59] Yashin AI, Arbeev KG, Wu D, Arbeeva LS, Kulminski A, Akushevich I(2013). How lifespan associated genes modulate aging changes: lessons from analysis of longitudinal data. Front Genet, 4:3
[60] Rattan SI(2012). Rationale and methods of discovering hormetins as drugs for healthy ageing. Expert Opin Drug Discov, 7:439-448
http://dx.doi.org/10.1517/17460441.2012.677430
[61] Rattan SIS(2004). Aging, anti-aging, and hormesis. Mech Age Dev, 125:285-289
http://dx.doi.org/10.1016/j.mad.2004.01.006
[62] Rattan SIS(2008). Hormesis in aging. Ageing Res Rev, 7:63-78
http://dx.doi.org/10.1016/j.arr.2007.03.002
[63] Rattan SIS(2008). Principles and practice of hormetic treatment of aging and age-related diseases. Hum Exp Toxicol, 27:151-157
http://dx.doi.org/10.1177/0960327107083409
[64] Fuchs E, Chen T(2013). A matter of life and death: self-renewal in stem cells. EMBO Rep, 14:39-48
http://118.145.16.217/magsci/article/article?id=19814502
[65] Kuranda K, Vargaftig J, de la Rochere P, Dosquet C, Charron D, Bardin F(2011). Age-related changes in human hematopoietic stem/progenitor cells. Aging Cell, 10:542-546
http://dx.doi.org/10.1111/j.1474-9726.2011.00675.x
[66] Rodgerson DO, Harris AG(2011). A comparison of stem cells for therapeutic use. Stem Cell Rev, 7:782-796
http://118.145.16.217/magsci/article/article?id=15629178
[67] Seppet E, Paasuke M, Conte M, Capri M, Franceschi C(2011). Ethical aspects of aging research. Biogerontology, 12:491-502
http://118.145.16.217/magsci/article/article?id=15699295
[68] Franceschi C, Valensin S, Bonafè M, Paolisso G, Yashin AI, Monti D(2000). The network and the remodeling theories of aging: historical background and new perspectives. Exp Gerontol, 35:879-896
http://dx.doi.org/10.1016/S0531-5565(00)00172-8
[69] Bartke A, Westbrook R(2012). Metabolic characteristics of long-lived mice. Front Genet, 3:288
[70] Fontana L, Partridge L, Longo VD(2010). Extending healthy life span--from yeast to humans. Science, 328:321-326
http://dx.doi.org/10.1126/science.1172539
[71] Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G(2013). The hallmarks of aging. Cell, 153:1194-1217
http://118.145.16.217/magsci/article/article?id=19655884
[72] Kim EB, Fang X, Fushan AA, Huang Z, Lobanov AV, Han L(2011). Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature, 479:223-227
http://dx.doi.org/10.1038/nature10533
[73] Perez VI, Buffenstein R, Masamsetti V, Leonard S, Salmon AB, Mele J(2009). Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. Proc Natl Acad Sci U S A, 106:3059-3064
http://dx.doi.org/10.1073/pnas.0809620106
[74] Brunet-Rossinni AK, Austad SN(2004). Ageing studies on bats: a review. Biogerontology, 5:211-222
http://118.145.16.217/magsci/article/article?id=17228689
[75] Seim I, Fang X, Xiong Z, Lobanov AV, Huang Z, Ma S(2013). Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii. Nat Commun, 4:2212
[76] Hamilton JB, Mestler GE(1969). Mortality and survival: comparison of eunuchs with intact men and women in a mentally retarded population. J Gerontol, 24:395-411
http://dx.doi.org/10.1093/geronj/24.4.395
[77] Min KJ, Lee CK, Park HN(2012). The lifespan of Korean eunuchs. Curr Biol, 22:R792-793
http://dx.doi.org/10.1016/j.cub.2012.06.036
[78] Gutteridge JM, Halliwell B(2010). Antioxidants: Molecules, medicines, and myths. Biochem Biophys Res Commun, 393:561-564
http://dx.doi.org/10.1016/j.bbrc.2010.02.071
[79] Hayes DP(2008). Adverse effects of nutritional inadequecy and excess: a hormetic model. Am J Clin Nutr, 88:578S-581S
[80] Le Bourg E(2005). Antioxidants and aging in human beings. Rattan SIS Aging Interventions and TherapiesSingaporeWorld Scientific Publishers85-107
[81] Wick G(2002). ‘Anti-aging’ medicine: does it exist? A critical discussion of ‘anti-aging health products’. Exp Gerontol, 37:1137-1140
http://dx.doi.org/10.1016/S0531-5565(02)00081-5
[82] Le Bourg E, Rattan SIS Mild stress and healthy aging: applying hormesis in aging research and interventionsDordrecht, The NetherlandsSpringer2008
[83] Rattan SIS, Le Bourg E Hormesis in health and diseaseBoca RatonCRC Press2013
[84] Rattan SIS, Demirovic D(2010). Hormesis can and does work in humans. Dose Response, 8:58-63
http://dx.doi.org/10.2203/dose-response.09-041.Rattan
[85] Singh R, Lakhanpal D, Kumar S, Sharma S, Kataria H, Kaur M(2011). Late-onset intermittent fasting dietary restriction as a potential intervention to retard age-associated brain function impairments in male rats. Age (Dordr)
[86] Rattan SIS, Fernandes RA, Demirovic D, Dymek B, Lima CF(2009). Heat stress and hormetin-induced hormesis in human cells: effects on aging, wound healing, angiogenesis and differentiation. Dose Response, 7:93-103
[87] Argyropoulou A, Aligiannis N, Trougakos IP, Skaltsounis AL(2013). Natural compounds with anti-ageing activity. Nat Prod Rep, 30:1412-1437
http://118.145.16.217/magsci/article/article?id=19749264
[88] Rattan SIS, Kryzch V, Schnebert S, Perrier E, Carine Nizard C(2013). Hormesis-based anti-aging products: a case study of a novel cosmetic. Dose Response, 11:99-108
http://dx.doi.org/10.2203/dose-response.11-054.Rattan
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