Genotypic and Phenotypic Aspects of Longevity: Results from a Sicilian Survey and Implication for the Prevention and Treatment of Age-related Diseases

Author(s): Giulia Accardi, Stefano Aprile, Giuseppina Candore, Calogero Caruso*, Rosanna Cusimano, Laura Cristaldi, Danilo Di Bona, Giovanni Duro, Damiano Galimberti, Caterina Maria Gambino, Mattia Emanuela Ligotti, Walter Mazzucco, Sonya Vasto, Anna Aiello.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 3 , 2019


Abstract:

Background: It is well known that long living individuals are a model of successful ageing and that the identification of both genetic variants and environmental factors that predispose to a long and healthy life is of tremendous interest for translational medicine.

Methods: We present the preliminary findings obtained from an ongoing study on longevity conducted on a sample of Sicilian long-lived individuals.

Results: We review the characteristics of longevity in Sicily, taking into account lifestyle, environment, genetics, hematochemical values, body composition and immunophenotype. In addition, we discuss the possible implications of our data for the prevention and/or treatment of age-related diseases.

Conclusion: As widely discussed in this review, the explanation of the role of genetics and lifestyle in longevity can provide important information on how to develop drugs and/or behaviours that can slow down or delay ageing. Thus, it will be possible to understand, through a “positive biology” approach, how to prevent and/or reduce elderly frailty and disability.

Keywords: Age-related diseases, body composition, genetics, immunosenescence, longevity, Sicily.

[1]
Avery P, Barzilai N, Benetos A, et al. Ageing, longevity, exceptional longevity and related genetic and non genetics markers: panel statement. Curr Vasc Pharmacol 2014; 12(5): 659-61.
[2]
Longo VD, Antebi A, Bartke A, et al. Interventions to Slow Aging in Humans: Are We Ready? Aging Cell 2015; 14(4): 497-510.
[3]
Caruso C, Passarino G, Puca A, Scapagnini G. “Positive biology”: the centenarian lesson. Immun Ageing 2012; 9(1): 5.
[4]
Passarino G, De Rango F, Montesanto A. Human longevity: Genetics or Lifestyle? It takes two to tango. Immun Ageing 2016; 13: 12.
[5]
Poulain M, Pes GM, Grasland C, et al. Identification of a geographic area characterized by extreme longevity in the Sardinia island: the AKEA study. Exp Gerontol 2004; 39(9): 1423-9.
[6]
Poulain M, Pes GM. The Blue Zones: areas of exceptional longevity around the world. Vienna Yearb Popul Res 2013; 11: 87-108.
[7]
Puca AA, Spinelli C, Accardi G, Villa F, Caruso C. Centenarians as a model to discover genetic and epigenetic signatures of healthy ageing. Mech Ageing Dev 2018; 174: 95-102.
[8]
Vasto S, Scapagnini G, Rizzo C, Monastero R, Marchese A, Caruso C. Mediterranean diet and longevity in Sicily: survey in a Sicani Mountains population. Rejuvenation Res 2012; 15(2): 184-8.
[9]
Vasto S, Rizzo C, Caruso C. Centenarians and diet: what they eat in the Western part of Sicily. Immun Ageing 2012; 9(1): 10.
[10]
Bürkle A, Caselli G, Franceschi C, et al. Pathophysiology of ageing, longevity and age related diseases. Immun Ageing 2007; 4: 4.
[11]
Vasto S, Buscemi S, Barera A, Di Carlo M, Accardi G, Caruso C. Mediterranean diet and healthy ageing: a Sicilian perspective. Gerontology 2014; 60(6): 508-18.
[14]
Taylor D. Physical activity is medicine for older adults. Postgrad Med J 2014; 90(1059): 26-32.
[15]
Marcuello A, González-Alonso J, Calbet JA, Damsgaard R, López-Pérez MJ, Díez-Sánchez C. Skeletal muscle mitochondrial DNA content in exercising humans. J Appl Physiol (1985) 2005. 99(4): 1372-7.
[16]
McPhee JS, French DP, Jackson D, Nazroo J, Pendleton N, Degens H. Physical activity in older age: perspectives for healthy ageing and frailty. Biogerontology 2016; 17(3): 567-80.
[17]
Broer L, Buchman AS, Deelen J, et al. GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy. J Gerontol A Biol Sci Med Sci 2015; 70(1): 110-8.
[18]
Corbo RM, Scacchi R, Apolipoprotein E, Apolipoprotein E. APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele? Ann Hum Genet 1999; 63(Pt 4): 301-10.
[19]
Schächter F, Faure-Delanef L, Guénot F, et al. Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 1994; 6(1): 29-32.
[20]
Hansen M, Hsu AL, Dillin A, Kenyon C. New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet 2005; 1(1): 119-28.
[21]
Honda Y, Honda S. The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J 1999; 13(11): 1385-93.
[22]
Aiello A, Accardi G, Candore G, et al. Nutrient sensing pathways as therapeutic targets for healthy ageing. Expert Opin Ther Targets 2017; 21(4): 371-80.
[23]
Revelas M, Thalamuthu A, Oldmeadow C, et al. Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity. Mech Ageing Dev 2018; 175: 24-34.
[24]
Di Bona D, Accardi G, Virruso C, Candore G, Caruso C. Association between genetic variations in the insulin/insulin-like growth factor (Igf-1) signaling pathway and longevity: a systematic review and meta-analysis. Curr Vasc Pharmacol 2014; 12(5): 674-81.
[25]
Caruso C, Accardi G, Virruso C, Candore G. Sex, gender and immunosenescence: a key to understand the different lifespan between men and women? Immun Ageing 2013; 10(1): 20.
[26]
Capri M, Salvioli S, Monti D, et al. Human longevity within an evolutionary perspective: the peculiar paradigm of a post-reproductive genetics. Exp Gerontol 2008; 43(2): 53-60.
[27]
Bae H, Gurinovich A, Malovini A, et al. Effects of FOXO3 Polymorphisms on Survival to Extreme Longevity in Four Centenarian Studies. J Gerontol A Biol Sci Med Sci 2018; 73(11): 1439-47.
[28]
Balistreri CR, Candore G, Accardi G, et al. Genetics of longevity. data from the studies on Sicilian centenarians. Immun Ageing 2012; 9(1): 8.
[29]
Incalcaterra E, Accardi G, Balistreri CR, et al. Pro-inflammatory genetic markers of atherosclerosis. Curr Atheroscler Rep 2013; 15(6): 329.
[30]
Licastro F, Candore G, Lio D, et al. Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing 2005; 2: 8.
[31]
Leonardi GC, Accardi G, Monastero R, Nicoletti F, Libra M. Ageing: from inflammation to cancer. Immun Ageing 2018; 15: 1.
[32]
Wongrakpanich S, Wongrakpanich A, Melhado K, Rangaswami J. A comprehensive review of non-steroidal anti-inflammatory drug use in the Elderly. Aging Dis 2018; 9(1): 143-50.
[33]
Azad MAK, Sarker M, Li T, Yin J. Probiotic species in the modulation of gut microbiota: an overview. BioMed Res Int 2018; 20189478630
[34]
Ambrose KR, Golightly YM. Physical exercise as non-pharmacological treatment of chronic pain: Why and when. Best Pract Res Clin Rheumatol 2015; 29(1): 120-30.
[35]
Minihane AM, Vinoy S, Russell WR, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr 2015; 114(7): 999-1012.
[36]
Gambino CM, Accardi G, Aiello A, et al. Effect of extra virgin olive oil and table olives on the immuneinflammatory responses: potential clinical applications. Endocr Metab Immune Disord Drug Targets 2018; 18(1): 14-22.
[37]
Aiello A, Guccione GD, Accardi G, Caruso C. What olive oil for healthy ageing? Maturitas 2015; 80(2): 117-8.
[38]
Virruso C, Accardi G, Colonna-Romano G, Candore G, Vasto S, Caruso C. Nutraceutical properties of extra-virgin olive oil: a natural remedy for age-related disease? Rejuvenation Res 2014; 17(2): 217-20.
[39]
Lio D, Malaguarnera M, Maugeri D, et al. Laboratory parameters in centenarians of Italian ancestry. Exp Gerontol 2008; 43(2): 119-22.
[40]
Carmienke S, Freitag MH, Pischon T, et al. General and abdominal obesity parameters and their combination in relation to mortality: a systematic review and meta-regression analysis. Eur J Clin Nutr 2013; 67(6): 573-85.
[41]
Cerhan JR, Moore SC, Jacobs EJ, et al. A pooled analysis of waist circumference and mortality in 650, 000 adults. Mayo Clin Proc 2014; 89(3): 335-45.
[42]
Hotchkiss JW, Leyland AH. The relationship between body size and mortality in the linked Scottish Health Surveys: cross-sectional surveys with follow-up. Int J Obes 2011; 35(6): 838-51.
[43]
Pérez LM, Pareja-Galeano H, Sanchis-Gomar F, Emanuele E, Lucia A, Gálvez BG. ‘Adipaging’: ageing and obesity share biological hallmarks related to a dysfunctional adipose tissue. J Physiol 2016; 594(12): 3187-207.
[44]
Beleigoli AM, Boersma E, Diniz Mde F, Lima-Costa MF, Ribeiro AL. Overweight and class I obesity are associated with lower 10-year risk of mortality in Brazilian older adults: the Bambuí Cohort Study of Ageing. PLoS One 2012; 7(12)e52111
[45]
Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA 2013; 309(1): 71-82.
[46]
Gallagher D, Visser M, Sepúlveda D, Pierson RN, Harris T, Heymsfield SB. How useful is body mass index for comparison of body fatness across age, sex, and ethnic groups? Am J Epidemiol 1996; 143(3): 228-39.
[47]
Kouvari M, Chrysohoou C, Tsiamis E, et al. The “overweight paradox” in the prognosis of acute coronary syndrome for patients with heart failure-A truth for all? A 10-year follow-up study. Maturitas 2017; 102: 6-12.
[48]
Romero-Corral A, Montori VM, Somers VK, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet 2006; 368(9536): 666-78.
[49]
Snijder MB, van Dam RM, Visser M, Seidell JC. What aspects of body fat are particularly hazardous and how do we measure them? Int J Epidemiol 2006; 35(1): 83-92.
[50]
De Lorenzo A, Bianchi A, Maroni P, et al. Adiposity rather than BMI determines metabolic risk. Int J Cardiol 2013; 166(1): 111-7.
[51]
Winter JE, MacInnis RJ, Wattanapenpaiboon N, Nowson CA. BMI and all-cause mortality in older adults: a meta-analysis. Am J Clin Nutr 2014; 99(4): 875-90.
[52]
Bera TK. Bioelectrical impedance methods for noninvasive health monitoring: a review. J Med Eng 2014; 2014381251
[53]
Accardi G, Caruso C. Immune-inflammatory responses in the elderly: an update. Immun Ageing 2018; 15: 11.
[54]
Potestio M, Pawelec G, Di Lorenzo G, et al. Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes. Exp Gerontol 1999; 34(5): 659-73.
[55]
Geiger H, Denkinger M, Schirmbeck R. Hematopoietic stem cell aging. Curr Opin Immunol 2014; 29: 86-92.
[56]
Colonna-Romano G, Buffa S, Bulati M, et al. B cells compartment in centenarian offspring and old people. Curr Pharm Des 2010; 16(6): 604-8.
[57]
Rubino G, Bulati M, Aiello A, et al. Sicilian centenarian offspring are more resistant to immune ageing. Aging Clin Exp Res 2019; 31(1): 125-33.
[58]
Viganò S, Perreau M, Pantaleo G, Harari A. Positive and negative regulation of cellular immune responses in physiologic conditions and diseases. Clin Dev Immunol 2012; 2012485781
[59]
Henson SM, Macaulay R, Kiani-Alikhan S, Akbar AN. The use of the inhibitory receptors for modulating the immune responses. Curr Pharm Des 2008; 14(26): 2643-50.
[60]
Henson SM, Macaulay R, Riddell NE, Nunn CJ, Akbar AN. Blockade of PD-1 or p38 MAP kinase signaling enhances senescent human CD8(+) T-cell proliferation by distinct pathways. Eur J Immunol 2015; 45(5): 1441-51.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 25
ISSUE: 3
Year: 2019
Page: [228 - 235]
Pages: 8
DOI: 10.2174/1381612825666190313115233
Price: $58

Article Metrics

PDF: 21
HTML: 4
EPUB: 1

Special-new-year-discount