Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: A proof of principle on type 2 diabetes

Garagnani, Paolo; Giuliani, Cristina; Pirazzini, Chiara; Olivieri, Fabiola; Bacalini, Maria Giulia; Ostan, Rita; Mari, Daniela; Passarino, Giuseppe; Monti, Daniela; Bonfigli, Anna Rita; Boemi, Massimo; Ceriello, Antonio; Genovese, Stefano; Sevini, Federica; Luiselli, Donata; Tieri, Paolo; Capri, Miriam; Salvioli, Stefano; Vijg, Jan; Suh, Yousin; Delledonne, Massimo; Testa, Roberto; Franceschi, Claudio

doi:10.18632/aging.100562

Cited by 55 publications

(35 citation statements)

References 66 publications

(77 reference statements)

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“…Many epidemiological studies have shown that older people have a higher blood glucose level compared with younger people, which results from the lower rate of glucose metabolism and insulin resistance (Stout 1994;Chang and Halter 2003). However, individuals with exceptional longevity maintain normal values of glucose level even in their old age because they are less likely to develop diabetes mellitus than control groups (Davey et al 2012;Garagnani et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Longitudinal and cross-sectional changes with age in selected anthropometric and physiological traits in hospitalized adults: an insight from the Polish Longitudinal Study of Aging (PLSA)

Chmielewski

Borysławski

Chmielowiec³

et al. 2015

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Longitudinal studies of aging concerning individuals with comparable lifestyle, diet, health profile, socioeconomic status, and income remain extraordinarily rare. The purposes of our ongoing project are as follows: (i) to collect extensive data on biological and medical aspects of aging in the Polish population, (ii) to determine factors affecting the rate and course of aging, (iii) to understand how aging unfolds as a dynamic and malleable process in ontogeny, and (iv) to find novel predictors of longevity. Our investigation followed 142 physically healthy asylum inmates, including 68 males and 74 females, for at least 25 years from the age of 45 years onward. Cross-sectional assessment involved 225 inmates, including 113 males and 112 females. All the patients lived for a very long time under similar and good environmental conditions at the hospital in Cibórz, Lubuskie Province. They maintained virtually the same daily schedule and lifestyle. The rate and direction of changes with age in selected anthropometric and physiological traits were determined using ANOVA, t-test, and regression analysis. There were sex differences in the rate and pattern of age-related changes in certain characteristics such as relative weight, red blood cell count, monocyte count, thymol turbidity value, systolic blood pressure, and body temperature. Body weight, the body mass index (BMI), and total bilirubin level increased with advancing age, while body height decreased with age in both sexes. In conclusion, the aging process was associated with many regressive alterations in biological traits in both sexes but the rate and pattern of these changes depended on biological factors such as age and sex. There were only few characteristics which did not change significantly during the period under study. On the basis of comparison between the pattern of longitudinal changes with aging and the pattern of cross-sectional changes with age in the analyzed traits, we were able to predict which pattern of changes is associated with longer lifespan.

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Section: Discussionmentioning

confidence: 99%

Longitudinal and cross-sectional changes with age in selected anthropometric and physiological traits in hospitalized adults: an insight from the Polish Longitudinal Study of Aging (PLSA)

Chmielewski

Borysławski

Chmielowiec³

et al. 2015

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“…Support for the premise that TL is involved in aging and disease comes from studies in which TLs have been positively associated with longevity (longer telomeres in centenarians; Atzmon et al, 2010; Garagnani et al, 2013) and negatively associated increased risk of cancer (patients with these conditions have shortened telomeres; Codd et al, 2013; Ma et al, 2011). A recent multiethnic epidemiological study of 100,000 people found that individuals whose telomeres were in the shortest 10% were approximately 23% more likely to die in the 3 years after measurement of their telomeres (Schaefer et al, 2012).…”

Section: Telomere Structure and Functionmentioning

confidence: 99%

An Integrative Review of Factors Associated with Telomere Length and Implications for Biobehavioral Research

Starkweather

Alhaeeri²,

Montpetit³

et al. 2014

Nursing Research

158

140

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Background Although telomere shortening occurs as a natural part of aging, there is now a robust body of research that suggests that there is a relationship between psychosocial, environmental, and behavioral factors and changes in telomere length. These factors need to be considered when integrating telomere measurement in biobehavioral research studies. Objectives This article provides a brief summary of the known facts about telomere biology and an integrative review of current human research studies that assessed relationships between psychosocial, environmental, or behavioral factors and telomere length. Methods An integrative review was conducted to examine human research studies that focused on psychosocial, environmental, and behavioral factors affecting telomere length and telomerase activity using the electronic databases PubMed/Medline and CINAHL from 2003 to the present. In addition to the known individual factors that are associated with telomere length, the results of the integrative review suggest that perceived stress, childhood adversities, major depressive disorder, educational attainment, physical activity, and sleep duration should also be measured. Discussion Multiple factors have been shown to affect telomere length. To advance understanding of the role of telomere length in health and disease risk, it will be important to further elucidate the mechanisms that contribute to telomere shortening.

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“…In the context of longevity, Garagnani et al (2013) argued that centenarians could be used as 'super controls' to assess the biological significance of genetic markers for age-related diseases, for Type 2 diabetes and the TCF7L2 genotypes. They noted marked reduced frequency of the diabetes-related T-allele of TCF7L2 in their super centenarian controls, but an enrichment of the homozygous CC-genotype, suggesting that the CC-genotype could be a strong protective variant, at least in their Italian centenarians likely to have been exposed to a Mediterranean diet.…”

Section: Tcf7l2 Gene Epigenetics and Mediterranean Dietmentioning

confidence: 99%

Living long and ageing well: is epigenomics the missing link between nature and nurture?

2015

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Human longevity is a complex trait and increasingly we understand that both genes and lifestyle interact in the longevity phenotype. Non-genetic factors, including diet, physical activity, health habits, and psychosocial factors contribute approximately 50% of the variability in human lifespan with another 25% explained by genetic differences. Family clusters of nonagenarian and centenarian siblings, who show both exceptional age-span and health-span, are likely to have inherited facilitatory gene groups, but also have nine decades of life experiences and behaviours which have interacted with their genetic profiles. Identification of their shared genes is just one small step in the link from genes to their physical and psychological profiles. Behavioural genomics is beginning to demonstrate links to biological mechanisms through regulation of gene expression, which directs the proteome and influences the personal phenotype. Epigenetics has been considered the missing link between nature and nurture. Although there is much that remains to be discovered, this article will discuss some of genetic and environmental factors which appear important in good quality longevity and link known epigenetic mechanisms to themes identified by nonagenarians themselves related to their longevity. Here we suggest that exceptional 90-year old siblings have adopted a range of behaviours and life-styles which have contributed to their ageing-well-phenotype and which link with important public health messages.

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Centenarians as super-controls to assess the biological relevance of genetic risk factors for common age-related diseases: A proof of principle on type 2 diabetes

Cited by 55 publications

References 66 publications

Longitudinal and cross-sectional changes with age in selected anthropometric and physiological traits in hospitalized adults: an insight from the Polish Longitudinal Study of Aging (PLSA)

Longitudinal and cross-sectional changes with age in selected anthropometric and physiological traits in hospitalized adults: an insight from the Polish Longitudinal Study of Aging (PLSA)

An Integrative Review of Factors Associated with Telomere Length and Implications for Biobehavioral Research

Living long and ageing well: is epigenomics the missing link between nature and nurture?

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