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Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.

ABSTRACT: Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl-xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune response, all associated to healthy aging. Indeed, centenarians display lower plasma cytochrome C levels, higher mitochondrial membrane potential and also less cellular damage accumulation than septuagenarians. Leukocyte chemotaxis and NK cell activity are significantly impaired in septuagenarians compared with young people whereas centenarians maintain them. To further ascertain the functional role of Bcl-xL in cellular aging, we found that lymphocytes from septuagenarians transduced with Bcl-xL display a reduction in senescent-related markers. Finally, to demonstrate the role of Bcl-xL in longevity at the organism level, C. elegans bearing a gain of function mutation in the Bcl-xL ortholog ced-9, showed a significant increase in mean and maximal life span. These results show that mRNA expression in centenarians is unique and reveals that Bcl-xL plays an important role in exceptional aging.

SUBMITTER: Borras C

PROVIDER: S-EPMC5270663 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.

Borras Consuelo C Abdelaziz Kheira M KM Gambini Juan J Serna Eva E Inglés Marta M de la Fuente Monica M Garcia Idoia I Matheu Ander A Sanchís Paula P Belenguer Angel A Errigo Alessandra A Avellana Juan-Antonio JA Barettino Ana A Lloret-Fernández Carla C Flames Nuria N Pes Gianni G Rodriguez-Mañas Leocadio L Viña Jose J

Aging 20161001 12

Centenarians not only enjoy an extraordinary aging, but also show a compression of morbidity. Using functional transcriptomic analysis of peripheral blood mononuclear cells (PMBC) we identified 1721 mRNAs differentially expressed by centenarians when compared with septuagenarians and young people. Sub-network analysis led us to identify Bcl-xL as an important gene up-regulated in centenarians. It is involved in the control of apoptosis, cellular damage protection and also in modulation of immune ...[more]

PMID: 27794564

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Project description:BackgroundExceptional aging, defined as reaching age 85 years, shows geographic inequalities that may depend on local environmental conditions. Links between particulate pollution-a well-recognized environmental risk factor-and exceptional aging have not been investigated.ObjectivesWe conducted a nationwide analysis of ~28 million adults in 3,034 United States counties to determine whether local PM2.5 levels (particulate matter < 2.5 μm in aerodynamic diameter) affected the probability of becoming 85- to 94-year-olds or centenarians (100- to 104-year-olds) in 2010 for individuals who were 55-64 or 70-74 years old, respectively, in 1980.MethodsWe used population-weighted regression models including county-level PM2.5 from hybrid land-use regression and geostatistical interpolation, smoking, obesity, sociodemographic, and age-specific migration variables.ResultsOn average, 2,295 and 71.4 per 10,000 of the 55- to 64- and 70- to 74-year-olds in 1980, respectively, remained in the 85- to 94- and 100- to 104-year-old population in 2010. An interquartile range (4.19 μg/m3) increase in PM2.5 was associated with 93.7 fewer 85- to 94-year-olds (p < 0.001) and 3.5 fewer centenarians (p < 0.05). These associations were nearly linear, were stable to model specification, and were detectable below the annual PM2.5 national standard. Exceptional aging was strongly associated with smoking, with an interquartile range (4.77%) increase in population who smoked associated with 181.9 fewer 85- to 94-year-olds (p < 0.001) and 6.4 fewer centenarians (p < 0.001). Exceptional aging was also associated with obesity rates and median income.ConclusionsCommunities with the most exceptional aging have low ambient air pollution and low rates of smoking, poverty, and obesity. Improvements in these determinants may contribute to increasing exceptional aging. Citation: Baccarelli AA, Hales N, Burnett RT, Jerrett M, Mix C, Dockery DW, Pope CA III. 2016. Particulate air pollution, exceptional aging, and rates of centenarians: a nationwide analysis of the United States, 1980-2010. Environ Health Perspect 124:1744-1750; http://dx.doi.org/10.1289/EHP197.

Dataset Information

Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.

Publications

Human exceptional longevity: transcriptome from centenarians is distinct from septuagenarians and reveals a role of Bcl-xL in successful aging.

Similar Datasets

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