Heat shock response by EBV-immortalized B-lymphocytes from centenarians and control subjects: a model to study the relevance of stress response in longevity.

'Successful aging', i.e. the ability to attain old age in relatively good health, is believed to be related to the capability to cope with different environmental stresses. Independently of their specific differentiation, all body cells respond to hyperthermia and other stresses with the production of Heat Shock Proteins (HSPs) that play an important role in cell survival. We investigated the heat shock response in B-lymphoid cell lines from 44 centenarians and 23 younger subjects, by studying both HSP70 synthesis and cell survival after hyperthermic treatment. Interestingly, no significant difference could be found between the two age groups as far as HSP70 synthesis was concerned; moreover, cell lines from centenarians appeared to be less prone to heat-induced apoptosis than lines from younger controls. These results, which are in contrast with previous findings showing an age-related decrease of the HSP70 synthesis and of hyperthermic response, corroborate the above mentioned hypothesis that the biological success of centenarians is due to the preservation of the capability to cope with stresses. An A/C polymorphism identified in the promoter region of HSP70-1 gene had been previously shown to affect the probability to attain longevity in females. To investigate if this effect was related to any influence of this polymorphism on HSP70 protein synthesis the correlation between A/C polymorphism and protein synthesis was investigated. We found that cells from AA centenarian females displayed a lower synthesis of HSP70.

Cytotoxic T lymphocyte antigen 4 polymorphism 49 (A>G) and migraine.

Migraine without aura (MO) and migraine with aura (MA) are disorders involving multiple environmental and genetic factors. The A/G polymorphism located within exon 1 of the gene encoding the cytotoxic T lymphocyte antigen 4 (CTLA-4) is associated with several HLA-associated multifactorial diseases. The CTLA-4 family shows a negative control on T-cell proliferation and cytokine production (TNF-alpha and IL-10). In the present study we investigated the contribution of the candidate gene CTLA-4 in migraine pathophysiology. Included in the study were 96 MO and 39 MA migraine patients and 106 healthy individuals as control group. The results showed no statistical difference of allele frequencies between patient group and control group. These results would indicate no association between MA and MO migraine and CTLA-4 polymorphism, excluding any possible role of the CTLA-4 gene as a genetic factor determining susceptibility to migraine.

Tumor necrosis factor gene polymorphism in migraine.

OBJECTIVE: To better define the involvement of human leukocyte antigen region (HLA) genes in migraine via an association study of the tumor necrosis factor (TNF) genes, located in the HLA class III region, with migraine with and without aura. BACKGROUND: Migraine without aura and migraine with aura are disorders involving multiple factors-environmental and genetic. In a previous study, we hypothesized a protective role for the HLA-DR2 antigen, providing additional basis for the proposed genetic heterogeneity between migraine without aura and migraine with aura. The cytokines produced by TNF genes are polypeptide effectors of inflammatory reaction and endothelial function. METHODS: Tumor necrosis factor (TNF)-308 (TNF-308A and TNF-308G alleles) and lymphotoxin alpha (TNFB*1 and TNFB*2 alleles) polymorphisms were analyzed by the NcoI-cleaved polymerase chain reaction-amplified fragments in 47 patients with migraine without aura, 32 patients with migraine with aura, and 101 migraine-free controls. RESULTS: The frequency of TNFB*2 allele was significantly increased in our patients with migraine without aura as compared with the control group (78.72% versus 61.4%, Pc =.004), but no significant differences were found between patients with migraine with aura and controls. Additionally, there was a significant decrease of TNFB*1 homozygotes in patients with migraine without aura compared with the control group (2.13% versus 16.8%, Pc =.0201). Carriage of the TNFB*2 allele confers a high risk for the development of migraine without aura. No significant association was found at TNF-308 polymorphism. CONCLUSION: These data support the hypothesis that lymphotoxin alpha could be a susceptibility gene in migraine without aura and confirm previous data indicating that migraine with and without aura are distinct entities with different genetic backgrounds.