IGF-1 Accelerates Cell Aging by Inhibiting POLD1 Expression.

Objective: The individual cascades of the insulin-like growth factor-1 (IGF-1) signaling pathway and the molecular mechanism of aging have not been fully clarified. In the current study, we explored the effect of DNA polymerase delta 1 (POLD1) on the IGF-1 signaling pathway in cell aging. Methods: First, we analyzed the relationship between IGF-1 and POLD1 expression in aging. To investigate the effect of IGF-1 on POLD1 expression and aging, the 2BS cells were incubated with young-age or old-age human serum, IGF-1 protein, or linsitinib. Next, the effect of IGF-1 on aging was examined in the 2BS cells with increased or decreased POLD1 expression to clarify the molecular mechanism. Results: In this study, we found that IGF-1 expression increased and POLD1 expression decreased with aging in human serum and hippocampal tissues of SAMP8 mice, and a negative relationship between IGF-1 and POLD1 expression was observed. Furthermore, the cells cultured with old-age human serum or IGF-1 showed lower POLD1 expression and more pronounced senescence characteristics, and the effect could be reversed by treatment with linsitinib or overexpression of POLD1, while the effect of linsitinib on cell aging could be reversed with the knockdown of POLD1. Conclusion: Taken collectively, our findings demonstrate that IGF-1 promotes aging by binding to IGF-1R and inhibiting the expression of POLD1. These findings offer a new target for anti-aging strategies.

Prognostic value of magnetic resonance imaging in patients with clinically isolated syndrome conversion to multiple sclerosis: a meta-analysis.

BACKGROUND: Numerous studies have investigated the associations of brain or spinal cord MRI with the risk of developing Multiple Sclerosis (MS) in people with Clinically Isolated Syndrome (CIS), however, the findings are uncertain. Therefore, we performed a meta-analysis based on 24 publications to comprehensively evaluate such associations. MATERIALS AND METHODS: The databases of EMBASE and MEDLINE (January 1980-August 2011) were searched electronically for all relevant studies. Data were extracted from each study independently by both reviewers using a predefined structured spreadsheet. The quality of each study was assessed independently by two reviewers according to Newcastle-Ottawa Scale for reading cohort study proposed by Deeks et al. The meta-analysis including 24 qualified studies was performed by using the Cochrane Collaborations RevMan5.0 software. RESULTS: Twenty-four identified studies met the inclusion criteria and minimum quality threshold. A meta-analysis of cohort studies indicated that the CISs having MRI lesions did have significantly increased risk for MS (risk ratio [RR] = 3.71, 95% confidence interval [CI], 3.27-4.21, P < 0.00001). In the subgroup analysis (according to the number of T2 lesions at baseline), the risk of developing MS in CIS patients with the medium MRI burden (4-9 lesions) was higher than with the low MRI burden (1-3 lesions) (RR = 0.66,95% CI, 0.45-0.95, P < 0.00001). While, no correlation was found in group between the medium MRI burden and the high MRI burden(>9 lesions) (RR = 0.97, 95% CI, 0.82-1.15, P = 0.72). Meanwhile, the CIS patients with abnormal baseline MRI, especially with infratentorial lesions, had a high risk of conversion to MS compared to patients without the such infratentorial lesions (RR = 1.37, % CI, 1.09-1.73, P = 0.0008). CONCLUSIONS: Despite some limitations, this meta-analysis established solid statistical evidence for an association between the presence or absence of MRI lesions within the brain or spinal cord MRI and the risk of developing MS, particularly for studies with large sample size. The CIS patients with abnormal baseline MRI, especially with infratentorial lesions, had a high risk of conversion to MS. However, this association warrants additional validation in larger and well designed studies.