scholarly journals The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1222
Author(s):  
Domitilla Mandatori ◽  
Letizia Pelusi ◽  
Valeria Schiavone ◽  
Caterina Pipino ◽  
Natalia Di Pietro ◽  
...  

Osteoporosis (OP) and vascular calcification (VC) represent relevant health problems that frequently coexist in the elderly population. Traditionally, they have been considered independent processes, and mainly age-related. However, an increasing number of studies have reported their possible direct correlation, commonly defined as “bone-vascular crosstalk”. Vitamin K2 (VitK2), a family of several natural isoforms also known as menaquinones (MK), has recently received particular attention for its role in maintaining calcium homeostasis. In particular, VitK2 deficiency seems to be responsible of the so-called “calcium paradox” phenomenon, characterized by low calcium deposition in the bone and its accumulation in the vessel wall. Since these events may have important clinical consequences, and the role of VitK2 in bone-vascular crosstalk has only partially been explained, this review focuses on its effects on the bone and vascular system by providing a more recent literature update. Overall, the findings reported here propose the VitK2 family as natural bioactive molecules that could be able to play an important role in the prevention of bone loss and vascular calcification, thus encouraging further in-depth studies to achieve its use as a dietary food supplement.

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 737 ◽  
Author(s):  
Hyun-Joo Park ◽  
Yeon Kim ◽  
Mi-Kyoung Kim ◽  
Jae Joon Hwang ◽  
Hyung Joon Kim ◽  
...  

Vascular calcification is the pathological deposition of calcium/phosphate in the vascular system and is closely associated with cardiovascular morbidity and mortality. Here, we investigated the role of gastrin-releasing peptide (GRP) in phosphate-induced vascular calcification and its potential regulatory mechanism. We found that the silencing of GRP gene and treatment with the GRP receptor antagonist, RC-3095, attenuated the inorganic phosphate-induced calcification of vascular smooth muscle cells (VSMCs). This attenuation was caused by inhibiting phenotype change, apoptosis and matrix vesicle release in VSMCs. Moreover, the treatment with RC-3095 effectively ameliorated phosphate-induced calcium deposition in rat aortas ex vivo and aortas of chronic kidney disease in mice in vivo. Therefore, the regulation of the GRP-GRP receptor axis may be a potential strategy for treatment of diseases associated with excessive vascular calcification.


2014 ◽  
Vol 29 (3) ◽  
pp. 172-177 ◽  
Author(s):  
Margueritta El Asmar ◽  
Joseph Naoum ◽  
Elias Arbid

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Anjali Chauhan ◽  
Jacob Hudobenko ◽  
Anthony Patrizz ◽  
Louise D McCullough

Introduction: GDF 11 is a member of the transforming growth factor β superfamily. Loss of GDF11 occurs with aging and declining levels correlate with several detrimental age-associated phenotypes in both peripheral tissues and brain. Restoration of GDF11 enhances neurogenesis and cognitive function in aged mice. Brain expression of GDF11 has not been investigated after stroke. Stroke differentially affects the elderly. In this work we examined the role of GDF11 in aging, stroke and its potential utility as a neuroprotective agent. Methods: Male C57/BL6NCrl young (2-3 months) and aged (19-21) mice were used. Brain GDF11 expression was evaluated in young and aged mice by western blot. Focal ischemia was induced with a transient middle cerebral artery occlusion (MCAO). Mice were randomly assigned into two groups and were subjected to 90 min MCAO. Group 1 received vehicle (phosphate buffered saline) and group 2 was administered rGDF11 (100 ug/kg., ip) at the onset of ischemia. In additional experiments, the efficacy of delayed treatment (3 h after ischemia) with rGDF11 was tested. These mice were subjected to a 60 min MCAO. Mice were euthanized after 24 hours and 7 days respectively and brains were harvested to estimate infarct area. Results: A significant decrease in brain GDF11 levels was observed in aged mice as compared to young (p<0.05). Additionally, a significant decline in brain GDF11 expression was observed after stroke at 24 hours vs. sham groups (p<0.05). A significant decrease in cortical and hemispheric infarct area was observed in the rGDF11 group (cortical 48.73±1.05; hemisphere 49.68±3.58) as compared to vehicle group (60.54±4.88; 61.35±6.03), when GDF was administered at the time of ischemia. Delayed treatment with rGDF11 also reduced infarct at 7 days. Conclusions: Brain GDF11 levels decline with age and after stroke. Supplementation with rGDF11 ameliorates stroke induced injury in young mice at 24h and 7 days. These finding suggest potential role of GDF11 in age and stroke. Restoration of age-related loss of GDF may be a viable therapy for stroke.


Blood ◽  
1988 ◽  
Vol 71 (6) ◽  
pp. 1726-1730
Author(s):  
KA Melez ◽  
LF Fries ◽  
BS Bender ◽  
T Quinn ◽  
MM Frank

Decreased immune functions have been suggested as a cause for the increased incidence of autoimmunity, malignancy, and infection in the elderly population. To assess the possible role of changes in macrophage function in the aging process we studied the Fc receptor- mediated clearance of IgG-coated erythrocytes in 56 healthy normal volunteers by following the removal of radiolabeled autologous erythrocytes. An age-related decrease in Fc-mediated clearance rates in both female and male subjects was found, which suggests a physiological decline of this macrophage function in older individuals.


Author(s):  
В. С. Мякотных ◽  
А. П. Сиденкова ◽  
Е. С. Остапчук ◽  
И. А. Кулакова ◽  
Н. А. Белых ◽  
...  

Высокий риск когнитивных расстройств у лиц пожилого и старческого возраста заставляет, с одной стороны, искать их причины, с другой - возможности профилактики. В связи с этим в последние годы получило распространение понятие когнитивного резерва, подразумевающего совокупность количественных параметров головного мозга и его способности сохранять высокую функциональную активность в процессе старения и на фоне связанной с возрастом патологии головного мозга. Представленный в статье материал на основе обзора научной литературы освещает два основных момента, касающихся возможности сохранения когнитивного резерва, - гендерный и образовательный факторы. Указывается на разные возможности женщин и мужчин, связанные со структурными и функциональными особенностями ЦНС у представителей разного пола, и на особую роль поддерживаемого в течение всей жизни образовательного процесса. Обозначена авторская позиция о необходимости разделения понятий образования и образованности, то есть уровня общей культуры и создания удобного инструмента для определения последнего. Это, в свою очередь, помогло бы в разработке модели когнитивного резерва, нацеленной на предотвращение трансформации физиологического когнитивного старения в патологическое. The high risk of cognitive disorders in the elderly and senile age makes, on the one hand, to look for their causes, on the other - the possibility of prevention. In this regard, in recent years, the concept of cognitive reserve has become widespread, implying a set of quantitative parameters of the brain and its ability to maintain high functional activity in the process of aging and against the background of age-related brain pathology. The material presented in the article on the basis of the review of scientific literature highlights two main points concerning the possibility of preserving the cognitive reserve-gender and educational factors. It is pointed to the different opportunities of women and men associated with the structural and functional characteristics of the Central nervous system in representatives of different sexes and the special role of the educational process supported throughout life. The author’s position on the need to separate the concepts of education and the level of General culture, and the creation of a convenient tool for determining the latter is indicated. This, in turn, would help in the development of a cognitive reserve model aimed at preventing the transformation of physiological cognitive aging into pathological aging.


2020 ◽  
Vol 21 (8) ◽  
pp. 2745
Author(s):  
Yukihiro Kohara ◽  
Ryuma Haraguchi ◽  
Riko Kitazawa ◽  
Yuuki Imai ◽  
Sohei Kitazawa

The functional role of the Hedgehog (Hh)-signaling pathway has been widely investigated in bone physiology/development. Previous studies have, however, focused primarily on Hh functions in bone formation, while its roles in bone resorption have not been fully elucidated. Here, we found that cyclopamine (smoothened (Smo) inhibitor), GANT-58 (GLI1 inhibitor), or GANT-61 (GLI1/2 inhibitor) significantly inhibited RANKL-induced osteoclast differentiation of bone marrow-derived macrophages. Although the inhibitory effects were exerted by cyclopamine or GANT-61 treatment during 0–48 h (early stage of osteoclast differentiation) or 48–96 h (late stage of osteoclast differentiation) after RANKL stimulation, GANT-58 suppressed osteoclast formation only during the early stage. These results suggest that the Smo-GLI1/2 axis mediates the whole process of osteoclastogenesis and that GLI1 activation is requisite only during early cellular events of osteoclastogenesis. Additionally, macrophage/osteoclast-specific deletion of Smo in mice was found to attenuate the aging phenotype characterized by trabecular low bone mass, suggesting that blockage of the Hh-signaling pathway in the osteoclast lineage plays a protective role against age-related bone loss. Our findings reveal a specific role of the Hh-signaling pathway in bone resorption and highlight that its inhibitors show potential as therapeutic agents that block osteoclast formation in the treatment of senile osteoporosis.


Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 223 ◽  
Author(s):  
Katsuhiko Suzuki

Reduced levels of physical activity in people’s daily lives cause the development of metabolic syndromes or age-related disorders. Chronic inflammation is now understood to be an underlying pathological condition in which inflammatory cells such as neutrophils and monocyte/macrophages infiltrate into fat and other tissues and accumulate when people become obese due to overeating and/or physical inactivity. Pro-inflammatory mediators such as cytokines that are secreted in excess from inflammatory cells will not only lead to the development of arteriosclerosis when they chronically affect blood vessels but also bring tissue degeneration and/or dysfunction to various organs. Chronic inflammation is also involved in sarcopenia that brings hypofunction in the elderly, dementia, osteoporosis, or cancer and negatively affects many chronic diseases and people’s healthy life expectancy. In this paper, outlines of such studies are introduced in terms of homeostatic inflammation, which occurs chronically due to the innate immune system and its abnormalities, while focusing on the efficacy of exercise from aspects of immunology and oxidative stress. The preventative effects of functional food ingredients in combination with exercise are also introduced and described. The challenges and future directions in understanding the role of exercise in the control of chronic inflammation are discussed.


Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1801 ◽  
Author(s):  
Bee Ling Tan ◽  
Mohd Esa Norhaizan

Despite an increase in life expectancy that indicates positive human development, a new challenge is arising. Aging is positively associated with biological and cognitive degeneration, for instance cognitive decline, psychological impairment, and physical frailty. The elderly population is prone to oxidative stress due to the inefficiency of their endogenous antioxidant systems. As many studies showed an inverse relationship between carotenoids and age-related diseases (ARD) by reducing oxidative stress through interrupting the propagation of free radicals, carotenoid has been foreseen as a potential intervention for age-associated pathologies. Therefore, the role of carotenoids that counteract oxidative stress and promote healthy aging is worthy of further discussion. In this review, we discussed the underlying mechanisms of carotenoids involved in the prevention of ARD. Collectively, understanding the role of carotenoids in ARD would provide insights into a potential intervention that may affect the aging process, and subsequently promote healthy longevity.


2011 ◽  
Vol 6 (2) ◽  
pp. 253-257 ◽  
Author(s):  
Takahiro Nakamura ◽  
◽  
Motoya Takagi ◽  
Shinnosuke Usui ◽  
◽  
...  

As we age, we change physically and mentally. As society ages, the birthrate decreases and the older worker’s social role increases in importance. The social role of the elderly is, however, threatened by the potential increase in age-related accidents. This research used 34,217 cases to explore and clarify the features of age-related accidents, classified by type, victim age –10 to 30s, 40 to 50s, and those aged 60 and over– and the number of absentee days due to accidents. Our results show that more time is needed for an older worker to return to the job after an accident than for a young worker. The importance of accident prevention for older workers is growing throughout industry. Ensuring such safety improves safety for workers of all ages. Issues involving age-related worker safety thus are related to the safety and well-being of workers of all generation.


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