Chronological Age and DNA Damage Accumulation in Blood Mononuclear Cells : A Linear Association in Healthy Humans after 50 Years of Age
Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, including DNA damage, progressive decline in organ function and chronic diseases. Since several features of the aging phenotype are closely related to defects in the DNA damage response (DDR) network, we have herein investigated the relationship between chronological age and DDR signals in peripheral blood mononuclear cells (PBMCs) from healthy individuals. DDR-associated parameters, including endogenous DNA damage (single-strand breaks and double-strand breaks (DSBs) measured by the alkaline comet assay (Olive Tail Moment (OTM); DSBs-only by γH2AX immunofluorescence staining), DSBs repair capacity, oxidative stress, and apurinic/apyrimidinic sites were evaluated in PBMCs of 243 individuals aged 18-75 years, free of any major comorbidity. While OTM values showed marginal correlation with age until 50 years (rs = 0.41, p = 0.11), a linear relationship was observed after 50 years (r = 0.95, p < 0.001). Moreover, individuals older than 50 years showed increased endogenous DSBs levels (γH2Ax), higher oxidative stress, augmented apurinic/apyrimidinic sites and decreased DSBs repair capacity than those with age lower than 50 years (all p < 0.001). Results were reproduced when we examined men and women separately. Prospective studies confirming the value of DNA damage accumulation as a biomarker of aging, as well as the presence of a relevant agethreshold, are warranted.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
---|---|
Enthalten in: |
International journal of molecular sciences - 24(2023), 8 vom: 12. Apr. |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Vlachogiannis, Nikolaos I [VerfasserIn] |
---|
Links: |
---|
Themen: |
Apurinic/apyrimidinic sites |
---|
Anmerkungen: |
Date Completed 01.05.2023 Date Revised 01.05.2023 published: Electronic Citation Status MEDLINE |
---|
doi: |
10.3390/ijms24087148 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM356118835 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM356118835 | ||
003 | DE-627 | ||
005 | 20231226065802.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.3390/ijms24087148 |2 doi | |
028 | 5 | 2 | |a pubmed24n1187.xml |
035 | |a (DE-627)NLM356118835 | ||
035 | |a (NLM)37108309 | ||
035 | |a (PII)7148 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Vlachogiannis, Nikolaos I |e verfasserin |4 aut | |
245 | 1 | 0 | |a Chronological Age and DNA Damage Accumulation in Blood Mononuclear Cells |b A Linear Association in Healthy Humans after 50 Years of Age |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 01.05.2023 | ||
500 | |a Date Revised 01.05.2023 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Aging is characterized by the progressive deregulation of homeostatic mechanisms causing the accumulation of macromolecular damage, including DNA damage, progressive decline in organ function and chronic diseases. Since several features of the aging phenotype are closely related to defects in the DNA damage response (DDR) network, we have herein investigated the relationship between chronological age and DDR signals in peripheral blood mononuclear cells (PBMCs) from healthy individuals. DDR-associated parameters, including endogenous DNA damage (single-strand breaks and double-strand breaks (DSBs) measured by the alkaline comet assay (Olive Tail Moment (OTM); DSBs-only by γH2AX immunofluorescence staining), DSBs repair capacity, oxidative stress, and apurinic/apyrimidinic sites were evaluated in PBMCs of 243 individuals aged 18-75 years, free of any major comorbidity. While OTM values showed marginal correlation with age until 50 years (rs = 0.41, p = 0.11), a linear relationship was observed after 50 years (r = 0.95, p < 0.001). Moreover, individuals older than 50 years showed increased endogenous DSBs levels (γH2Ax), higher oxidative stress, augmented apurinic/apyrimidinic sites and decreased DSBs repair capacity than those with age lower than 50 years (all p < 0.001). Results were reproduced when we examined men and women separately. Prospective studies confirming the value of DNA damage accumulation as a biomarker of aging, as well as the presence of a relevant agethreshold, are warranted | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Comet assay | |
650 | 4 | |a DNA damage response | |
650 | 4 | |a apurinic/apyrimidinic sites | |
650 | 4 | |a chronological age | |
650 | 4 | |a double-strand breaks repair capacity | |
650 | 4 | |a endogenous DNA damage | |
650 | 4 | |a oxidative stress | |
700 | 1 | |a Ntouros, Panagiotis A |e verfasserin |4 aut | |
700 | 1 | |a Pappa, Maria |e verfasserin |4 aut | |
700 | 1 | |a Kravvariti, Evrydiki |e verfasserin |4 aut | |
700 | 1 | |a Kostaki, Evangelia Georgia |e verfasserin |4 aut | |
700 | 1 | |a Fragoulis, Georgios E |e verfasserin |4 aut | |
700 | 1 | |a Papanikolaou, Christina |e verfasserin |4 aut | |
700 | 1 | |a Mavroeidi, Dimitra |e verfasserin |4 aut | |
700 | 1 | |a Bournia, Vasiliki-Kalliopi |e verfasserin |4 aut | |
700 | 1 | |a Panopoulos, Stylianos |e verfasserin |4 aut | |
700 | 1 | |a Laskari, Katerina |e verfasserin |4 aut | |
700 | 1 | |a Arida, Aikaterini |e verfasserin |4 aut | |
700 | 1 | |a Gorgoulis, Vassilis G |e verfasserin |4 aut | |
700 | 1 | |a Tektonidou, Maria G |e verfasserin |4 aut | |
700 | 1 | |a Paraskevis, Dimitrios |e verfasserin |4 aut | |
700 | 1 | |a Sfikakis, Petros P |e verfasserin |4 aut | |
700 | 1 | |a Souliotis, Vassilis L |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t International journal of molecular sciences |d 2008 |g 24(2023), 8 vom: 12. Apr. |w (DE-627)NLM185552161 |x 1422-0067 |7 nnns |
773 | 1 | 8 | |g volume:24 |g year:2023 |g number:8 |g day:12 |g month:04 |
856 | 4 | 0 | |u http://dx.doi.org/10.3390/ijms24087148 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 24 |j 2023 |e 8 |b 12 |c 04 |