Theories of biological aging: Genes, proteins, and free radicals

Traditional categorization of theories of aging into programmed and stochastic ones is outdated and obsolete. Biological aging is considered to occur mainly during the period of survival beyond the natural or essential lifespan (ELS) in Darwinian terms. Organisms survive to achieve ELS by virtue of genetically determined longevity assuring maintenance and repair systems (MRS). Aging at the molecular level is characterized by the progressive accumulation of molecular damage caused by environmental and metabolically generated free radicals, by spontaneous errors in biochemical reactions, and by nutritional components. Damages in the MRS and other pathways lead to age-related failure of MRS, molecular heterogeneity, cellular dysfunctioning, reduced stress tolerance, diseases and ultimate death. A unified theory of biological aging in terms of failure of homeodynamics comprising of MRS, and involving genes, milieu and chance, is acquiring a definitive shape and wider acceptance. Such a theory also establishes the basis for testing and developing effective means of intervention, prevention and modulation of aging.

[1]  S. Rattan Biogerontology: The Next Step , 2000, Annals of the New York Academy of Sciences.

[2]  B. Halliwell The antioxidant paradox , 2000, The Lancet.

[3]  M. Rautalahti,et al.  Antioxidants and carcinogenesis. , 1994, Annals of medicine.

[4]  T. Kirkwood Evolution of ageing , 1977, Nature.

[5]  R. Holliday From DNA modification to epigenetics , 1998, Journal of Genetics.

[6]  R. Holliday Ageing research in the next century , 2004, Biogerontology.

[7]  J. Menninger,et al.  Erythromycin slows aging of Saccharomyces cerevisiae. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[8]  W. Forbes,et al.  The Free Radical Theory of Aging: A Critique and Unresolved Questions , 1992, Canadian Journal on Aging / La Revue canadienne du vieillissement.

[9]  Jeffrey M. Hausdorff,et al.  Fractal dynamics in physiology: Alterations with disease and aging , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. Sen,et al.  Handbook of oxidants and antioxidants in exercise , 2000 .

[11]  Yoshiro Saito,et al.  Lipid peroxidation: mechanisms, inhibition, and biological effects. , 2005, Biochemical and biophysical research communications.

[12]  C. Kenyon The Plasticity of Aging: Insights from Long-Lived Mutants , 2005, Cell.

[13]  S. Rattan Problems and paradigms: Beyond the present crisis in gerontology , 1985 .

[14]  T. Johnson A personal retrospective on the genetics of aging , 2004, Biogerontology.

[15]  K. Christensen,et al.  Association Between Low Self-Rated Health and Heterozygosity for −110A > C Polymorphism in the Promoter Region of HSP70-1 in Aged Danish Twins , 2004, Biogerontology.

[16]  É. Bourg,et al.  Can dietary restriction increase longevity in all species, particularly in human beings? Introduction to a debate among experts , 2006, Biogerontology.

[17]  S. Husain,et al.  Oxidants, antioxidants and carcinogenesis. , 2002, Indian journal of experimental biology.

[18]  A. Hipkiss Errors, mitochondrial dysfunction and ageing , 2004, Biogerontology.

[19]  S. Olshansky,et al.  No truth to the fountain of youth. , 2002, Scientific American.

[20]  T. Kirkwood,et al.  Accuracy of tRNA charging and codon: anticodon recognition; relative importance for cellular stability. , 1993, Journal of theoretical biology.

[21]  R. Holliday Understanding ageing. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[22]  T. Nyström Translational fidelity, protein oxidation, and senescence: lessons from bacteria , 2002, Ageing Research Reviews.

[23]  R. Holliday Streptomycin, Errors in Mitochondria and Ageing , 2005, Biogerontology.

[24]  A. Bürkle Physiology and pathophysiology of poly(ADP‐ribosyl)ation * , 2001, BioEssays : news and reviews in molecular, cellular and developmental biology.

[25]  Bertrand Friguet,et al.  The ubiquitin–proteasome system at the crossroads of stress-response and ageing pathways: A handle for skin care? , 2006, Ageing Research Reviews.

[26]  Kaare Christensen,et al.  The quest for genetic determinants of human longevity: challenges and insights , 2006, Nature Reviews Genetics.

[27]  David A Padgett,et al.  How stress influences the immune response. , 2003, Trends in immunology.

[28]  R. Effros Genetic alterations in the ageing immune system: impact on infection and cancer , 2003, Mechanisms of Ageing and Development.

[29]  Ana Maria Cuervo,et al.  Protein degradation and aging , 2005, Experimental Gerontology.

[30]  J. Baynes From life to death – the struggle between chemistryand biology during aging: the Maillard reaction as an amplifier of genomic damage , 2004, Biogerontology.

[31]  N. Barzilai,et al.  Biological evidence for inheritance of exceptional longevity , 2005, Mechanisms of Ageing and Development.

[32]  R. Holliday The current status of the protein error theory of aging , 1996, Experimental Gerontology.

[33]  A. D. Grey Mitochondrial Free Radical Theory of Aging , 2021, Encyclopedia of Gerontology and Population Aging.

[34]  G. Pawelec Immunosenescence and human longevity , 2004, Biogerontology.

[35]  G. Ashcroft,et al.  Ageing and wound healing , 2004, Biogerontology.

[36]  A. Pandey,et al.  Bioinformatics and Proteomics Approaches for Aging Research , 2005, Biogerontology.

[37]  E. Medrano,et al.  The emerging role of epigenetics in cellular and organismal aging , 2003, Experimental Gerontology.

[38]  Keshav K. Singh Mitochondria Damage Checkpoint, Aging, and Cancer , 2006, Annals of the New York Academy of Sciences.

[39]  Suresh I. S. Rattan,et al.  Synthesis, modifications, and turnover of proteins during aging , 1996, Experimental Gerontology.

[40]  L. Loeb,et al.  The mitochondrial theory of aging and its relationship to reactive oxygen species damage and somatic mtDNA mutations. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[41]  R. Gelman,et al.  A putative gene causes variability in lifespan among genotypically identical mice , 1998, Nature Genetics.

[42]  T. Kirkwood,et al.  Mitochondrial mutations, cellular instability and ageing: modelling the population dynamics of mitochondria. , 1993, Mutation research.

[43]  B. Friguet,et al.  Enzymatic reactions involved in the repair of oxidized proteins , 2004, Experimental Gerontology.

[44]  H. Meserve,et al.  Time of our lives , 1989, Journal of Religion and Health.

[45]  A. Yashin,et al.  Measuring the genetic influence in modulating the human life span: gene–environment interaction and the sex-specific genetic effect , 2004, Biogerontology.

[46]  A. Jackson,et al.  Marker loci associated with life span in genetically heterogeneous mice. , 1998, The journals of gerontology. Series A, Biological sciences and medical sciences.

[47]  S. Rattan Aging interventions and therapies , 2005 .

[48]  Thomas B. L. Kirkwood,et al.  Stress, DNA damage and ageing — an integrative approach , 2001, Experimental Gerontology.

[49]  M. J. Coon,et al.  Cytochrome P-450 : multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms , 1991 .

[50]  B. Clark,et al.  Understanding and Modulating Ageing , 2005, IUBMB life.

[51]  K. Davies,et al.  Decreased proteolysis caused by protein aggregates, inclusion bodies, plaques, lipofuscin, ceroid, and 'aggresomes' during oxidative stress, aging, and disease. , 2004, The international journal of biochemistry & cell biology.

[52]  D. Ziegler,et al.  The enzymes of detoxication. , 1983, The Journal of biological chemistry.

[53]  R. Short Why we age , 1996, Nature.

[54]  L. Gavrilov,et al.  The reliability theory of aging and longevity. , 2001, Journal of theoretical biology.

[55]  Suresh I. S. Rattan,et al.  The Nature of Gerontogenes and Vitagenes: Antiaging Effects of Repeated Heat Shock on Human Fibroblasts , 1998, Annals of the New York Academy of Sciences.

[56]  T. Zglinicki,et al.  Free Radical Production and Antioxidant Defense: A Primer , 2003 .

[57]  George M. Martin The Werner Mutation: Does it Lead to a “Public” or “Private” Mechanism of Aging? , 1997, Molecular medicine.

[58]  P. Verbeke,et al.  HEAT SHOCK RESPONSE AND AGEING: MECHANISMS AND APPLICATIONS , 2001, Cell biology international.

[59]  T. Kirkwood Evolution of ageing , 2002, Mechanisms of Ageing and Development.

[60]  R. Gelman,et al.  Murine chromosomal regions correlated with longevity. , 1988, Genetics.

[61]  É. Bourg,et al.  Is Lifespan Extension Accompanied by Improved Antioxidant Defences? A Study of Superoxide Dismutase and Catalase in Drosophila Melanogaster Flies that Lived in Hypergravity at a Young Age , 2004, Biogerontology.

[62]  Suresh I. S. Rattan,et al.  Transcriptional and Translational Dysregulation During Aging , 2003 .

[63]  D. Harman Free Radical Theory of Aging: An Update , 2006, Annals of the New York Academy of Sciences.

[64]  H. Gutzeit,et al.  Interaction of stressors and the limits of cellular homeostasis. , 2001, Biochemical and biophysical research communications.

[65]  Lloyd Demetrius,et al.  Caloric restriction, metabolic rate, and entropy. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[66]  S. Olshansky,et al.  Biological evidence for limits to the duration of life , 2004, Biogerontology.

[67]  Z. Medvedev AN ATTEMPT AT A RATIONAL CLASSIFICATION OF THEORIES OF AGEING , 1990, Biological reviews of the Cambridge Philosophical Society.

[68]  Paul A. C. Cloos,et al.  Post-Translational Modifications of Proteins: Implications for Aging, Antigen Recognition, and Autoimmunity , 2004, Biogerontology.

[69]  Peter Riederer,et al.  AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs? , 2004, Biogerontology.

[70]  S. Rattan Aging intervention, prevention, and therapy through hormesis. , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[71]  S. Rattan Anti‐ageing strategies: prevention or therapy? , 2005 .

[72]  Jay Schulkin,et al.  Allostasis, Homeostasis, and the Costs of Physiological Adaptation: Preface , 2004 .

[73]  E. Stadtman,et al.  Protein oxidation by the cytochrome P450 mixed-function oxidation system. , 2005, Biochemical and biophysical research communications.

[74]  P. Srivastava,et al.  Heat shock proteins: the fountainhead of innate and adaptive immune responses , 2000, Cell stress & chaperones.

[75]  S. Jay Olshansky,et al.  At the Heart of Aging: is it Metabolic Rate or Stability? , 2005, Biogerontology.

[76]  Gail Jenkins,et al.  Molecular mechanisms of skin ageing , 2002, Mechanisms of Ageing and Development.

[77]  S. Rattan,et al.  Ageing--a biological perspective. , 1995, Molecular aspects of medicine.

[78]  R. M. Howes The Free Radical Fantasy , 2006, Annals of the New York Academy of Sciences.

[79]  Praveen Kumar Sharma,et al.  Estrogen receptor α expression in mice kidney shows sex differences during aging , 2004, Biogerontology.

[80]  Suresh I. S. Rattan Homeostasis, Homeodynamics, and Aging , 2007 .

[81]  G. Martin Genetic Modulation of Senescent Phenotypes in Homo sapiens , 2005, Cell.

[82]  M. Picard,et al.  Increased longevity of EF-1α high-fidelity mutants in Podospora anserina , 1994 .

[83]  T. Kirkwood Time of our lives , 2005 .

[84]  Frederick W. Alt,et al.  DNA Repair, Genome Stability, and Aging , 2005, Cell.

[85]  Charles A. Janeway,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:How the immune system works to protect the host from infection: A personal view , 2001 .

[86]  R. Holliday Understanding Ageing: Author index , 1995 .

[87]  V. Srivastava,et al.  Replicative enzymes and ageing: importance of DNA polymerase alpha function to the events of cellular ageing , 2002, Ageing Research Reviews.

[88]  T. Taguchi,et al.  Age-dependent changes in DNA polymerase fidelity and proofreading activity during cellular aging , 1999, Mechanisms of Ageing and Development.

[89]  J. Issa Epigenetic variation and human disease. , 2002, The Journal of nutrition.

[90]  S. Rattan Gerontogenes: real or virtual? , 1995, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[91]  D. Wallace A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine , 2005, Annual review of genetics.

[92]  R. Holliday Aging is No Longer an Unsolved Problem in Biology , 2006, Annals of the New York Academy of Sciences.

[93]  T. Lindahl,et al.  Quality control by DNA repair. , 1999, Science.

[94]  V. Bohr,et al.  Repair of oxidative DNA damage in nuclear and mitochondrial DNA, and some changes with aging in mammalian cells. , 2002, Free radical biology & medicine.

[95]  Bertrand Friguet,et al.  Impairment of proteasome structure and function in aging. , 2002, The international journal of biochemistry & cell biology.

[96]  T. Nyström Aging in bacteria. , 2002, Current opinion in microbiology.

[97]  A. Hallen Accumulation of insoluble protein and aging , 2004, Biogerontology.

[98]  E. Stadtman,et al.  Free radical-mediated oxidation of free amino acids and amino acid residues in proteins , 2003, Amino Acids.

[99]  M. Rossignol,et al.  Deletion and dosage modulation of the eEF1A gene inPodospora anserina: effect on the life cycle , 2004, Biogerontology.

[100]  L. Urban,et al.  Single nucleotide polymorphisms: aging and diseases , 2004, Biogerontology.

[101]  R. Aspinall Longevity and the immune response , 2004, Biogerontology.

[102]  T C Matise,et al.  A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4 , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[103]  C. Franceschi,et al.  The allele (A)-110 in the promoter region of the HSP70-1 gene is unfavorable to longevity in women , 2004, Biogerontology.

[104]  M. D. Temple,et al.  Complex cellular responses to reactive oxygen species. , 2005, Trends in cell biology.

[105]  T. Grune Oxidative stress, aging and the proteasomal system , 2004, Biogerontology.

[106]  K. Davies,et al.  Free radical biology – terminology and critical thinking , 2004, FEBS letters.

[107]  F. Yates Order and complexity in dynamical systems: Homeodynamics as a generalized mechanics for biology , 1994 .

[108]  U. Brunk,et al.  Testing the “garbage” accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy , 2004, Biogerontology.

[109]  George Suji,et al.  Glucose, glycation and aging , 2004, Biogerontology.

[110]  C. Franceschi,et al.  Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians , 2005, Mechanisms of Ageing and Development.