RESUMO
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.
Assuntos
Quebras de DNA de Cadeia Dupla , Leucócitos Mononucleares , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Leucócitos Mononucleares/fisiologia , Estudos Prospectivos , Dano ao DNA , Envelhecimento/genética , Reparo do DNARESUMO
OBJECTIVE: To study the prevalence of primary biliary cirrhosis (PBC) and its progression in patients with primary Sjögren's syndrome (SS). METHODS: We investigated 410 patients with primary SS, without history of liver disease, for the presence of PBC based on a retrospective review of clinical, biochemical, immunologic, and histologic data. RESULTS: Thirty-six (8.8%) patients had cholestatic liver biochemistry. Of them, 21 (5.1%) had positive antimitochondrial autoantibodies (AMA) detected by indirect immunofluorescence, while 15 were AMA-negative. Ten of the 21 AMA-positive patients and 7 of the 15 AMA-negative patients were further investigated with liver biopsy, the result of which was compatible with PBC in all but one (AMA-negative) patient. Overall, 27 (6.6%) patients had definite (n=10), probable (n=11), or AMA-negative (n=6) PBC. Pathologically, most PBC lesions were stage 1. Five patients had a second liver biopsy, with no significant histological deterioration. CONCLUSION: PBC is a rather uncommon development in patients with primary SS. The disease appears to be pathologically mild, with a propensity for slow progression, as assessed clinically, biochemically, and histologically.