Browsing by Person "Grune, Tilman"

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Association of Torquetenovirus Viremia with physical frailty and cognitive impairment in three independent European cohorts
(2023) Giacconi, Robertina; Laffon, Blanca; Costa, Solange; Teixeira-Gomes, Armanda; Maggi, Fabrizio; Macera, Lisa; Spezia, Pietro Giorgio; Piacenza, Francesco; Bürkle, Alexander; Moreno-Villanueva, María; Bonassi, Stefano; Valdiglesias, Vanessa; Teixeira, Joao Paulo; Dollé, Martijn E.T.; Rietman, M. Liset; Jansen, Eugène; Grune, Tilman; Gonos, Efstathios S.; Franceschi, Claudio; Capri, Miriam; Weinberger, Birgit; Sikora, Ewa; Stuetz, Wolfgang; Toussaint, Olivier; Debacq-Chainiaux, Florence; Hervonen, Antti; Hurme, Mikko; Slagboom, P. Eline; Schön, Christiane; Bernhardt, Jürgen; Breusing, Nicolle; Pásaro, Eduardo; Maseda, Ana; Lorenzo-López, Laura; Millán-Calenti, José Carlos; Provinciali, Mauro; Malavolta, Marco
Introduction: Immunosenescence and inflammaging have been implicated in the pathophysiology of frailty. Torquetenovirus (TTV), a single-stranded DNA anellovirus, the major component of the human blood virome, shows an increased replication rate with advancing age. An elevated TTV viremia has been associated with an impaired immune function and an increased risk of mortality in the older population. The objective of this study was to analyze the relation between TTV viremia, physical frailty, and cognitive impairment. Methods: TTV viremia was measured in 1,131 nonfrail, 45 physically frail, and 113 cognitively impaired older adults recruited in the MARK-AGE study (overall mean age 64.7 ± 5.9 years), and then the results were checked in two other independent cohorts from Spain and Portugal, including 126 frail, 252 prefrail, and 141 nonfrail individuals (overall mean age: 77.5 ± 8.3 years). Results: TTV viremia ≥4log was associated with physical frailty (OR: 4.69; 95% CI: 2.06–10.67, p < 0.0001) and cognitive impairment (OR: 3.49, 95% CI: 2.14–5.69, p < 0.0001) in the MARK-AGE population. The association between TTV DNA load and frailty status was confirmed in the Spanish cohort, while a slight association with cognitive impairment was observed (OR: 1.33; 95% CI: 1.000–1.773), only in the unadjusted model. No association between TTV load and frailty or cognitive impairment was found in the Portuguese sample, although a negative association between TTV viremia and MMSE score was observed in Spanish and Portuguese females. Conclusions: These findings demonstrate an association between TTV viremia and physical frailty, while the association with cognitive impairment was observed only in the younger population from the MARK-AGE study. Further research is necessary to clarify TTV’s clinical relevance in the onset and progression of frailty and cognitive decline in older individuals.
Nuclear activation of proteasome in oxidative stress and aging
(2009) Catalgol, Betul; Grune, Tilman
Poly(ADP-ribosyl)ation reactions are of interest in recent years and they take place in DNA repair in different processes especially following oxidative nuclear damage. Proteasomal reactions also take place in repair following oxidative nuclear damage with the degradation of oxidized histones. Antitumor chemotherapy is generally believed to act via the oxidation of nuclear material in the tumor cells. Adaptation to oxidative stress appears to be one element in the development of long-term resistance to many chemotherapeutic drugs. The 20S proteasome has been shown to be largely responsible for the degradation of oxidatively modified proteins in the nucleus. Tumor cells are supposed to have a higher nuclear proteasome activity than do nonmalignant cells. Poly(ADP-ribosyl)ation reactions take place in the tumor cells as a consequence of chemotherapy. Such a reaction might occur with the 20S proteasome ?which is known to increase the activity- and also with histones ?which is firstly shown to decrease the degradation in this study. After hydrogen peroxide treatment of HT22 cells, degradation of the model peptide substrate suc-LLVY-MCA and degradation of oxidized histones in nuclei increased accompanied by an increase in PARP-1 mRNA expression. In the recovery of the level of protein carbonyls, single strand breaks and 8-OHdG, proteasome and PARP-1 were shown to play a role together. This was tested with inhibitor treatments. The proteasomal activation following poly(ADP-ribosyl)ation of proteasome and the decrease in poly(ADP-ribosyl)ation of histones and increase in the proteasomal degradation of histones following H2O2 treatment confirmed our hypothesis. The second part of the thesis shows the changes in PARP-1 and proteasome in different aged fibroblasts with population doublings 19, 36, and 56. The nuclear protective mechanisms were shown to be effected during the senescence process. PARP-1 protein amount decreased whereas there was no change in proteasome amount. PARP activation following H2O2 treatment increased only in young and middle aged cells. In the nuclear extracts of young and old cells, poly(ADP-ribosyl)ation potentials were tested with NAD+ addition into the reaction. In addition to that active proteasome and PARP enzymes were added into the reaction and proteasome activity was measured. With active PARP, proteasome activity was increased both in young and old cells whereas there was no increase in old cells without PARP addition. These results show that proteasome activation is mainly limited by PARP activity. Taken together all results demonstrate the importance of PARP mediated proteasome activation in the repair of oxidatively damaged chromatin.
Uncovering the relationship between selenium status, age, health, and dietary habits: Insights from a large population study including nonagenarian offspring from the MARK-AGE project
(2023) Giacconi, Robertina; Piacenza, Francesco; Aversano, Valentina; Zampieri, Michele; Bürkle, Alexander; Villanueva, María Moreno; Dollé, Martijn E.T.; Jansen, Eugène; Grune, Tilman; Gonos, Efstathios S.; Franceschi, Claudio; Capri, Miriam; Weinberger, Birgit; Sikora, Ewa; Toussaint, Olivier; Debacq-Chainiaux, Florence; Stuetz, Wolfgang; Slagboom, Pieternella Eline; Bernhardt, Jürgen; Fernández-Sánchez, Maria Luisa; Provinciali, Mauro; Malavolta, Marco
An inadequate selenium (Se) status can accelerate the aging process, increasing the vulnerability to age-related diseases. The study aimed to investigate plasma Se and Se species in a large population, including 2200 older adults from the general population (RASIG), 514 nonagenarian offspring (GO), and 293 GO Spouses (SGO). Plasma Se levels in women exhibit an inverted U-shaped pattern, increasing with age until the post-menopausal period and then declining. Conversely, men exhibit a linear decline in plasma Se levels with age. Subjects from Finland had the highest plasma Se values, while those from Poland had the lowest ones. Plasma Se was influenced by fish and vitamin consumption, but there were no significant differences between RASIG, GO, and SGO. Plasma Se was positively associated with albumin, HDL, total cholesterol, fibrinogen, and triglycerides and negatively associated with homocysteine. Fractionation analysis showed that Se distribution among plasma selenoproteins is affected by age, glucometabolic and inflammatory factors, and being GO or SGO. These findings show that sex-specific, nutritional, and inflammatory factors play a crucial role in the regulation of Se plasma levels throughout the aging process and that the shared environment of GO and SGO plays a role in their distinctive Se fractionation.