SIRT4 in ageing.

Ageing is a phenomenon in which cells, tissues and organs undergo systemic pathological changes as individuals age, leading to the occurrence of ageing-related diseases and the end of life. It is associated with many phenotypes known as ageing characteristics, such as genomic instability, nutritional imbalance, mitochondrial dysfunction, cell senescence, stem cell depletion, and an altered microenvironment. The sirtuin family (SIRT), known as longevity proteins, is thought to delay ageing and prolong life, and mammals, including humans, have seven family members (SIRT1-7). SIRT4 has been studied less among the sirtuin family thus far, but it has been reported that it has important physiological functions in organisms, such as promoting DNA damage repair, participating in the energy metabolism of three substances, inhibiting inflammatory reactions and apoptosis, and regulating mitochondrial function. Recently, some studies have demonstrated the involvement of SIRT4 in age-related processes, but knowledge in this field is still scarce. Therefore, this review aims to analyse the relationship between SIRT4 and ageing characteristics as well as some age-related diseases (e.g., cardiovascular diseases, metabolic diseases, neurodegenerative diseases and cancer).

Adiponectin-Transfected Endothelial Progenitor Cells Have Protective Effects After 2-Hour Middle-Cerebral Artery Occlusion in Rats With Type 2 Diabetes Mellitus.

Objectives: This present study aimed to examine the effects of adiponectin-transfected endothelial progenitor cells (LV-APN-EPCs) on cerebral ischemia-reperfusion injury in rats with type 2 diabetes mellitus (T2DM) and to explore the underlying mechanisms. Methods: Seventy male Sprague-Dawley rats with T2DM were randomly divided into sham, phosphate-buffered saline (PBS), LV-APN-EPCs, LV-EPCs, and EPCs groups. Transient middle cerebral artery occlusion (MCAO) was induced by the intraluminal suture method. After 1 h of reperfusion, the five interventions were performed by tail-vein injections. The modified neurological severity score (mNSS) was used to assess neurological function before and on days 1, 7, and 14 after MCAO. After 14 days, magnetic resonance imaging scanning, hematoxylin and eosin staining, terminal dUTP nick-end labeling staining, Western blotting analysis, cluster of differentiation (CD) 31 immunofluorescence, and enzyme-linked immunosorbent assay were used to evaluate infarct rate, morphological damage, cell apoptosis, and microvessel density. Results: Compared with PBS, LV-EPCs, and EPCs groups, the LV-APN-EPCs group showed significantly lower mNSS score, lower infarct rate, and less morphological damage (all P < 0.05). In addition, compared with other groups, the LV-APN-EPCs group had significantly increased levels of B cell lymphoma/leukemia-2 (Bcl-2) protein, CD31+ microvessels, endothelial nitric oxide synthase, and vascular endothelial growth factor, and decreased levels of Bcl-2-associated X protein and neuronal apoptosis in the peri-infarct cortex (all P < 0.05). Conclusion: These results suggest that LV-APN-EPCs exert protective effects against cerebral ischemia-reperfusion injury in T2DM rats by increasing angiogenesis.

Association between red blood cell distribution width and white matter hyperintensities: A large-scale cross-sectional study.

BACKGROUND: Red blood cell distribution width (RDW) is a strong prognostic marker for various medical conditions, such as ischemic strokes. However, the relationships between higher RDW and the subtypes of white matter hyperintensities (WMHs) remain unclear. Hence, this study aimed to thoroughly evaluate the relationships between RDW and the subtypes of WMHs. PATIENTS AND METHODS: This cross-sectional study was a retrospective analysis of hospital database (Dongguan Medical System, from April 2015 to February 2017). The presence and subtypes of WMHs were evaluated using Fazekas score with the T2WI-FLAIR brain images from a 1.5-T MRI system. The overall sample was randomly split in half. One of the two split-half samples was used for determining the optimal cutoff value of higher RDW and another for further statistical analyses. RESULTS: A total of 555 subjects with WMHs and 642 controls were recruited. The optimal cutoff value of higher RDW was 13.25%. Logistic regression revealed that higher RDW (≥13.25%) was positively associated with periventricular WMHs (adjusted OR = 1.81, 95% CI: 1.16-2.82, p = .009). However, higher RDW was not associated with total WMHs (adjusted OR = 1.52, 95% CI: 0.99-2.33, p = .057) and deep WMHs (adjusted OR = 1.21, 95% CI: 0.76-1.94, p = .426). CONCLUSION: Our findings suggested that higher RDW may be independently associated with periventricular WMHs, but not with total WMHs and deep WMHs.

The Protective Effect of Adiponectin-Transfected Endothelial Progenitor Cells on Cognitive Function in D-Galactose-Induced Aging Rats.

Aging is a multifactorial process involving the cumulative effects of inflammation, oxidative stress, and mitochondrial dynamics, which can produce complex structural and biochemical alterations to the nervous system and lead to dysfunction of microcirculation, blood-brain barrier (BBB), and other problems in the brain. Long-term injection of D-galactose (D-gal) can induce chronic inflammation and oxidative stress, accelerating aging. The model of accelerated aging with long-term administration of D-gal have been widely used in anti-aging studies, due to the increase of chronic inflammation and decline of cognition that similarity with natural aging in animals. However, despite extensive researches in the D-gal-induced aging rats, studies on their microvasculature remain limited. Endothelial progenitor cells (EPCs), which are precursors to endothelial cells (ECs), play a significant role in the repair and regeneration process of endogenous blood vessel, and adiponectin (APN), a protein derived from adipocyte, has many effects on protective vascular endothelium and anti-inflammatory. Recently, many studies have shown that APN can promote improvements in cognitive function. Under these circumstances, we investigated the neuroprotective effect of the APN-transfected EPC (APN-EPC) treatment on rats after administration with D-gal and explored the likely underlying mechanisms. Compared to model group for D-gal administration, better cognitive function and denser microvessels were significantly found in the APN-EPC treatment group, and indicated APN-EPC treatment in aging rats could improve the cognitive dysfunction and microvessel density. The level of proinflammatory cytokines IL-1ß, IL-6, and TNF-α, activated astrocytes and apoptosis rate were significantly reduced in the APN-EPC group compared with the model group, showed that APN-EPCs alleviated the neuroinflammation in aging rats. In addition, the APN-EPC group inhibited the decrease of BBB-related proteins claudin-5, occludin, and Zo-1 in aging rats and attenuated BBB dysfunction significantly. These results of our study indicated that APN-EPC treatment in D-gal-induced aging rats have a positive effect on improving cognitive and BBB dysfunction, increasing angiogenesis, and reducing neuroinflammation and apoptosis rate. This research suggests that cell therapy via gene modification may provide a safe and effective approach for the treatment of age-related neurogenerative diseases.