The biological age of the heart is consistently younger than chronological age

Pavanello, Sofia; Campisi, Manuela; Fabozzo, Assunta; Cibin, Giorgia; Tarzia, Vincenzo; Toscano, Giuseppe; Gerosa, Gino

doi:10.1038/s41598-020-67622-1

Cited by 36 publications

(44 citation statements)

References 43 publications

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“…Furthermore, the advanced/accelerated aging of the lung in respect to the blood arising from our work, confirms that tissues and organs in our body may age at different rates within the same individuals [40], as we have already proved on donors' heart where DNAmAge is consistently younger than that of blood [23].…”

Section: Discussionsupporting

confidence: 86%

“…Determining the two most prominent biomarkers of biological age, DNAmAge and TL, with an almost totally automated workflow, is also a strong point of our study. To assess DNAmAge, we applied the method proposed by Zbieć-Piekarska et al [21] on data from five CpG sites using the locus-specific technology pyrosequencing with some modification as described by Pavanello et al [22,23], which makes the technical analysis achievable in few hours. It is noteworthy that pyrosequencing has the potential for multiplexing, which can simplify the protocol and reduce the cost of technical analysis.…”

Section: Discussionmentioning

confidence: 99%

“…DNA was extracted from whole blood using the QIAamp DNA Mini kit (QIAGEN, Milano, Italy) on a QIAcube System (QIAGEN, Milano, Italy) for automated high-throughput DNA purification, according to a customized protocol as previously described [23]. In particular, 400 µL of whole blood from each sample were processed for DNA extraction.…”

Section: Dna Extraction From Blood Samplesmentioning

confidence: 99%

“…DNAmAge was determined by analysis the methylation levels from selected markers using bisulfite conversion and Pyrosequencing® methodology as previously reported [22,23]. This method is based on determination of the methylation level of a set of five markers (ELOVL2, C1orf132, KLF14, TRIM59 and FHL2) in genomic DNA, as described by Zbieć-Piekarska et al [21] with some modifications based on the fact that the method was almost completely automated using the PyroMark Q48 Autoprep (QIAGEN, Milano, Italy) [22,23]. AgeAcc was calculated as the difference between the detected DNAmAge of lung cells and blood leucocytes and the chronological age of patients.…”

Section: Dnamage Analysis and Ageacc Estimationmentioning

confidence: 99%

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Biological Age in COPD Patients Reveals an Accelerated Lung Aging

Pavanello

Campisi

Bordin

et al. 2021

Preprint

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Chronic obstructive pulmonary disease (COPD), the third leading cause of death worldwide, shows striking clinical aging-associated features of lung. We tested the hypothesis that lung biological aging in COPD is accelerated. Biological aging was assessed by mitotic telomere length (TL) and non-mitotic age-dependent methylation changes in specific CpGs (DNAmAge) of lung cells, obtained from induced sputum, and peripheral blood leucocytes in 18 COPD patients (72.4±7.7 years; 50% males), clinically appraised by lung function and blood parameters. DNAmAge (67.4±5.80 vs 61.6±5.40 years; p=0.0003), AgeAcc (-4.5±5.02 vs -10.8±3.50 years; p=0.0003) and TL attrition (1.05±0.35 vs 1.48±0.21 T/S; p=0.0341) are higher in lung than blood in the same patients. Blood DNAmAge (r=0.927245; p=0.0026) and AgeAcc (r=0.916445; p=0.0037), but not TL, highly correlate with that of lung. Therefore, blood can be a proxy indicator of lung biological age. Multiple regression analyses show that both blood DNAmAge and AgeAcc decrease (i.e., younger) in patients with combined inhaled corticosteroids (ICS) therapy (p=0.0494 and p=0.0553) and FEV1% enhancement (p=0.0254; p=0.0296). In conclusion, the new finding, that lung of COPD patients is remarkably biologically older than blood, opens new research challenge on novel therapeutic approaches to counteract this key aspect of the disease.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Dna Extraction From Blood Samplesmentioning

confidence: 99%

Section: Dnamage Analysis and Ageacc Estimationmentioning

confidence: 99%

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Biological Age in COPD Patients Reveals an Accelerated Lung Aging

Pavanello

Campisi

Bordin

et al. 2021

Preprint

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“…A powerful emerging marker of non-mitotic cellular aging is the epigenetic age often defined as DNA methylation age (DNAmAge) (7,8). DNAmAge in human (9-11) is assessed from methylation at a species-specific subset of cytosine-guanine dyads (CpG), and it is strongly correlated with chronological age (9)(10)(11)(12)(13). Development of epigenetic predictors has addressed to an "epigenetic clock" theory of aging, according to which the difference between DNAmAge and chronological age is defined as "age acceleration" (AgeAcc) (14), which is indicative of altered biological functions (8) and elevated risk for morbidity and mortality (15).…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation-Based Age Prediction and Telomere Length Reveal an Accelerated Aging in Induced Sputum Cells Compared to Blood Leukocytes: A Pilot Study in COPD Patients

et al. 2021

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Aging is the predominant risk factor for most degenerative diseases, including chronic obstructive pulmonary disease (COPD). This process is however very heterogeneous. Defining the biological aging of individual tissues may contribute to better assess this risky process. In this study, we examined the biological age of induced sputum (IS) cells, and peripheral blood leukocytes in the same subject, and compared these to assess whether biological aging of blood leukocytes mirrors that of IS cells. Biological aging was assessed in 18 COPD patients (72.4 ± 7.7 years; 50% males). We explored mitotic and non-mitotic aging pathways, using telomere length (TL) and DNA methylation-based age prediction (DNAmAge) and age acceleration (AgeAcc) (i.e., difference between DNAmAge and chronological age). Data on demographics, life style and occupational exposure, lung function, and clinical and blood parameters were collected. DNAmAge (67.4 ± 5.80 vs. 61.6 ± 5.40 years; p = 0.0003), AgeAcc (−4.5 ± 5.02 vs. −10.8 ± 3.50 years; p = 0.0003), and TL attrition (1.05 ± 0.35 vs. 1.48 ± 0.21 T/S; p = 0.0341) are higher in IS cells than in blood leukocytes in the same patients. Blood leukocytes DNAmAge (r = 0.927245; p = 0.0026) and AgeAcc (r = 0.916445; p = 0.0037), but not TL, highly correlate with that of IS cells. Multiple regression analysis shows that both blood leukocytes DNAmAge and AgeAcc decrease (i.e., younger) in patients with FEV1% enhancement (p = 0.0254 and p = 0.0296) and combined inhaled corticosteroid (ICS) therapy (p = 0.0494 and p = 0.0553). In conclusion, new findings from our work reveal a differential aging in the context of COPD, by a direct quantitative comparison of cell aging in the airway with that in the more accessible peripheral blood leukocytes, providing additional knowledge which could offer a potential translation into the disease management.

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