Background: Adiposity has been shown to be linked with atypical energy-related symptoms (AES) of depression. We used genomics to separate the effect of adiposity from that of metabolic... Show moreBackground: Adiposity has been shown to be linked with atypical energy-related symptoms (AES) of depression. We used genomics to separate the effect of adiposity from that of metabolic dysregulations to examine whether the link between obesity and AES is dependent on the presence of metabolic dysregulations. Method: Data were from NEO (n = 5734 individuals) and NESDA (n = 2238 individuals) cohorts, in which the Inventory of Depressive Symptomatology (IDS-SR30) was assessed. AES profile was based on four symptoms: increased appetite, increased weight, low energy level, and leaden paralysis. We estimated associations between AES and two genetic risk scores (GRS) indexing increasing total body fat with (metabolically unhealthy adiposity, GRS-MUA) and without (metabolically healthy adiposity, GRS-MHA) metabolic dysregulations. Results: We validated that both GRS-MUA and GRS-MHA were associated with higher total body fat in NEO study, but divergently associated with biomarkers of metabolic health (e.g., fasting glucose and HDL-cholesterol) in both cohorts. In the pooled results, per standard deviation, GRS-MUA was specifically associated with a higher AES score (beta = 0.03, 95%CI: 0.01; 0.05), while there was no association between GRS-MHA and AES (beta =-0.01, 95%CI:-0.03; 0.01). Conclusion: These results suggest that the established link between adiposity and AES profile emerges in the presence of metabolic dysregulations, which may represent the connecting substrate between the two conditions. Show less
Piacenza, F.; Giacconi, R.; Costarelli, L.; Basso, A.; Burkle, A.; Moreno-Villanueva, M.; ... ; Malavolta, M. 2021
The analysis of copper (Cu) and zinc (Zn) along with their major serum carriers, albumin (Alb) and ceruloplasmin (Cp), could provide information on the capacity of humans to maintain homeostasis of... Show moreThe analysis of copper (Cu) and zinc (Zn) along with their major serum carriers, albumin (Alb) and ceruloplasmin (Cp), could provide information on the capacity of humans to maintain homeostasis of metals (metallostasis). However, their relationship with aging, sex, body mass index, as well as with nutritional and inflammatory markers was never investigated in a large-scale study. Here, we report results from the European large-scale cross-sectional study MARK-AGE in which Cu, Zn, Alb, Cp, as well as nutritional and inflammatory parameters were determined in 2424 age-stratified participants (35-75 years), including the general population (RASIG), nonagenarian offspring (GO), a well-studied genetic model of longevity, and spouses of GO (SGO). In RASIG, Cu to Zn ratio and Cp to Alb ratio were higher in women than in men. Both ratios increased with aging because Cu and Cp increased and Alb and Zn decreased. Cu, Zn, Alb, and Cp were found associated with several inflammatory as well as nutritional biomarkers. GO showed higher Zn levels and higher Zn to Alb ratio compared to RASIG, but we did not observe significant differences with SGO, likely as a consequence of the low sample size of SGO and the shared environment. Our results show that aging, sex, body mass index, and GO status are characterized by different levels of Cu, Zn, and their serum carrier proteins. These data and their relationship with inflammatory biomarkers support the concept that loss of metallostasis is a characteristic of inflammaging. Show less
Opstal, A.M. van; Kaal, I.; Berg-Huysmans, A.A. van den; Hoeksma, M.; Blonk, C.; Pijl, H.; ... ; Grond, J. van der 2019
The overall hypothesis of the Switchbox study is that maintenance of homeostasis is pivotal for maintenance of health in old age. Therefore, the aim of this thesis as part of the Switchbox study,... Show moreThe overall hypothesis of the Switchbox study is that maintenance of homeostasis is pivotal for maintenance of health in old age. Therefore, the aim of this thesis as part of the Switchbox study, was to expand our knowledge of homeostatic mechanisms at old age, thus trying to unravel underlying mechanisms of healthy human longevity. The focus of this thesis will be on analysis of the HPT-axis and HPA-axis in participants who have the propensity to reach old age in good health compared to age-matched controls. In humans, we are able to assess the 'function' of the HPT- and HPA- axes by measuring the key hormones involved as well as physiological parameters that are affected by these systems (heart rate, metabolism) under different conditions (in rest and during stress). Show less
