Remodelling of biological parameters during human ageing: evidence for complex regulation in longevity and in type 2 diabetes

Factor structure analyses have revealed the presence of specific biological system markers in healthy humans and diseases. However, this type of approach in very old persons and in type 2 diabetes (T2DM) is lacking. A total sample of 2,137 Italians consisted of two groups: 1,604 healthy and 533 with T2DM. Age (years) was categorized as adults (≤65), old (66–85), oldest old (>85–98) and centenarians (≥99). Specific biomarkers of routine haematological and biochemical testing were tested across each age group. Exploratory factorial analysis (EFA) by principal component method with Varimax rotation was used to identify factors including related variables. Structural equation modelling (SEM) was applied to confirm factor solutions for each age group. EFA and SEM identified specific factor structures according to age in both groups. An age-associated reduction of factor structure was observed from adults to oldest old in the healthy group (explained variance 60.4% vs 50.3%) and from adults to old in the T2DM group (explained variance 57.4% vs 44.2%). Centenarians showed three-factor structure similar to those of adults (explained variance 58.4%). The inflammatory component became the major factor in old group and was the first one in T2DM. SEM analysis in healthy subjects suggested that the glucose levels had an important role in the oldest old. Factorial structure change during healthy ageing was associated with a decrease in complexity but showed an increase in variability and inflammation. Structural relationship changes observed in healthy subjects appeared earlier in diabetic patients and later in centenarians.

[1]  S. Maggi,et al.  Components of the metabolic syndrome and incidence of diabetes in elderly Italians: the Italian Longitudinal Study on Aging. , 2006, Atherosclerosis.

[2]  L. Ferrucci,et al.  A Nutritional Index Predicting Mortality in the Nursing Home , 1994, Journal of the American Geriatrics Society.

[3]  E. Nakamura,et al.  Further evaluation of the basic nature of the human biological aging process based on a factor analysis of age-related physiological variables. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[4]  T. Hasegawa,et al.  Factor analysis of lifestyle-related factors in 12,525 urban Japanese subjects. , 2005, Journal of atherosclerosis and thrombosis.

[5]  G. Paolisso,et al.  Age‐related insulin resistance: is it an obligatory finding? The lesson from healthy centenarians , 2001, Diabetes/metabolism research and reviews.

[6]  C. Franceschi,et al.  Reduced susceptibility to peroxidation of erythrocyte plasma membranes from centenarians , 2002, Experimental Gerontology.

[7]  T. Deutschle,et al.  Nasal biomarker profiles in acute and chronic rhinosinusitis , 2005, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[8]  G. Castellani,et al.  Inflammaging and anti-inflammaging: A systemic perspective on aging and longevity emerged from studies in humans , 2007, Mechanisms of Ageing and Development.

[9]  R. P. McDonald,et al.  Structural Equations with Latent Variables , 1989 .

[10]  C. Caruso,et al.  Inflammation, genetic background and longevity , 2010, Biogerontology.

[11]  H. Christensen,et al.  Search for a Common Cause Factor amongst Cognitive, Speed and Biological Variables Using Narrow Age Cohorts , 2006, Gerontology.

[12]  L. Peltonen,et al.  Genetics of Healthy Aging in Europe , 2007, Annals of the New York Academy of Sciences.

[13]  S. Klein,et al.  Aging, adiposity, and calorie restriction. , 2007, JAMA.

[14]  S. Kolvraa,et al.  Genetics of human longevity with emphasis on the relevance of HSP70 as candidate genes. , 2007, Frontiers in bioscience : a journal and virtual library.

[15]  L. Ferrucci,et al.  Measuring systemic inflammatory regulation in older adults: evidence and utility. , 2009, Rejuvenation research.

[16]  G. Rossi,et al.  Diagnosis and Classification of Diabetes Mellitus The information that follows is based largely on the reports of the Expert Committee on the Diagnosis and Classification of Diabetes (Diabetes Care 20:1183–1197, 1997, and Diabetes Care 26:3160–3167, 2003). , 2008, Diabetes Care.

[17]  G. Paolisso,et al.  Glucose regulation and oxidative stress in healthy centenarians , 2003, Experimental Gerontology.

[18]  G. Castellani,et al.  Systems biology and longevity: an emerging approach to identify innovative anti-aging targets and strategies. , 2010, Current pharmaceutical design.

[19]  Katsuhiko Yano,et al.  FOXO3A genotype is strongly associated with human longevity , 2008, Proceedings of the National Academy of Sciences.

[20]  K. Yano,et al.  Caloric Restriction, the Traditional Okinawan Diet, and Healthy Aging , 2007, Annals of the New York Academy of Sciences.

[21]  C. Franceschi.  Inflammaging as a major characteristic of old people: can it be prevented or cured? , 2007, Nutrition reviews.

[22]  H. Tissenbaum,et al.  Converging Pathways in Lifespan Regulation , 2009, Current Biology.

[23]  C. Franceschi,et al.  A cluster analysis to define human aging phenotypes , 2007, Biogerontology.

[24]  B. Tabachnick,et al.  Using Multivariate Statistics , 1983 .

[25]  Pui-Yan Kwok,et al.  Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity , 2009, Aging cell.

[26]  P. Froguel,et al.  Genetic associations with human longevity at the APOE and ACE loci , 1994, Nature Genetics.

[27]  A. Yashin,et al.  Exceptional survivors have lower age trajectories of blood glucose: lessons from longitudinal data , 2010, Biogerontology.

[28]  Claudio Franceschi,et al.  The Genetics of Human Longevity , 2006, Annals of the New York Academy of Sciences.

[29]  João Pedro de Magalhães,et al.  Meta-analysis of age-related gene expression profiles identifies common signatures of aging , 2009, Bioinform..

[30]  Christian Fuchsberger,et al.  Heritability analysis of life span in a semi-isolated population followed across four centuries reveals the presence of pleiotropy between life span and reproduction. , 2011, The journals of gerontology. Series A, Biological sciences and medical sciences.

[31]  C. Franceschi,et al.  Genes, ageing and longevity in humans: Problems, advantages and perspectives , 2006, Free radical research.

[32]  P. Brantley,et al.  The multidimensional health locus of control scales: testing the factorial structure in sample of African American medical patients. , 2009, Ethnicity & disease.

[33]  C. Dunnett.  A Multiple Comparison Procedure for Comparing Several Treatments with a Control , 1955 .

[34]  Age , 2000, BMJ : British Medical Journal.

[35]  Yongmei Liu,et al.  Association between inflammatory components and physical function in the health, aging, and body composition study: a principal component analysis approach. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[36]  Mary Ann Ottinger,et al.  Aging in Rhesus Monkeys: Relevance to Human Health Interventions , 2004, Science.

[37]  K. Choi,et al.  Factor analysis of the metabolic syndrome among elderly Koreans—the South‐west Seoul Study , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[38]  D. Mari,et al.  Human longevity within an evolutionary perspective: The peculiar paradigm of a post-reproductive genetics , 2008, Experimental Gerontology.

[39]  M. Memo,et al.  Why do centenarians escape or postpone cancer? The role of IGF-1, inflammation and p53 , 2009, Cancer Immunology, Immunotherapy.

[40]  Y. Khader,et al.  Factor analysis of cardiometabolic risk factors clustering in children and adolescents. , 2011, Metabolic syndrome and related disorders.

[41]  D. Willcox,et al.  Oxidative Stress and Longevity in Okinawa: An Investigation of Blood Lipid Peroxidation and Tocopherol in Okinawan Centenarians , 2011, Current gerontology and geriatrics research.

[42]  Jason W. Osborne,et al.  Best practices in exploratory factor analysis: four recommendations for getting the most from your analysis. , 2005 .

[43]  J. Tuomilehto,et al.  The metabolic syndrome defined by factor analysis and incident type 2 diabetes in a chinese population with high postprandial glucose. , 2004, Diabetes care.

[44]  A. Yashin,et al.  The network and the remodeling theories of aging: historical background and new perspectives , 2000, Experimental Gerontology.

[45]  M. Bonafè,et al.  Genetic polymorphism in long-lived people: Cues for the presence of an insulin/IGF-pathway-dependent network affecting human longevity , 2009, Molecular and Cellular Endocrinology.

[46]  Arie Budovsky,et al.  The Human Ageing Genomic Resources: online databases and tools for biogerontologists , 2009, Aging cell.