Influence of age on wound healing and fibrosis

Kapetanaki, Maria G.; Mora, Ana L.; Rojas, Mauricio

doi:10.1002/path.4122

Cited by 81 publications

(59 citation statements)

References 157 publications

(166 reference statements)

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“…2D). Fibrosis is a hallmark of aging in many organs (26,27). We found that blood vessels in islets of aged mice contained more laminin, a biomarker of fibrosis (28) (Fig.…”

Section: Aged Pancreatic Islets Have Inflamed and Fibrotic Blood Vessmentioning

confidence: 88%

Young capillary vessels rejuvenate aged pancreatic islets

Almaça

Molina

Drigo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

116

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Pancreatic islets secrete hormones that play a key role in regulating blood glucose levels (glycemia). Age-dependent impairment of islet function and concomitant dysregulation of glycemia are major health threats in aged populations. However, the major causes of the age-dependent decline of islet function are still disputed. Here we demonstrate that aging of pancreatic islets in mice and humans is notably associated with inflammation and fibrosis of islet blood vessels but does not affect glucose sensing and the insulin secretory capacity of islet beta cells. Accordingly, when transplanted into the anterior chamber of the eye of young mice with diabetes, islets from old mice are revascularized with healthy blood vessels, show strong islet cell proliferation, and fully restore control of glycemia. Our results indicate that beta cell function does not decline with age and suggest that islet function is threatened by an age-dependent impairment of islet vascular function. Strategies to mitigate age-dependent dysregulation in glycemia should therefore target systemic and/or local inflammation and fibrosis of the aged islet vasculature.A ging leads to progressive decline of various homeostatic processes in mammals, including a deteriorating regulation of blood glucose levels. Pancreatic islets are small organs composed of endocrine cells that secrete the major hormones insulin, glucagon, and somatostatin, which play a key role in regulating blood glucose levels. Age-dependent dysfunction of islets and the concomitant dysregulation of blood glucose levels increase the risk for type 2 diabetes (1), which in turn contributes to other age-related chronic diseases. In general, it has been assumed that aging causes an intrinsic dysfunction of the insulin-secreting beta cells through reduced proliferative capacity and/or defective insulin secretion (1-9). However, there have been numerous reports that age-dependent impairment of glucose homeostasis is not just a result of intrinsic, age-dependent dysfunction of islets but is also caused by systemic factors. For example, islet function may be compromised by age-related increases in adiposity (10, 11) and by bloodborne factors (12), or it could be affected indirectly by agerelated deficiencies in vascular remodeling (13). Thus, the replicative decline of old pancreatic beta cells can be attributed to systemic factors (12). Recent studies identified factors present in young blood that reverse age-related cognitive impairments and induce vascular remodeling and regeneration in the brain and skeletal muscle (14-16), but so far it has not been feasible to discriminate systemic influences from aging factors intrinsic to islet endocrine cells. Here we address the long-standing question of whether the age-dependent impairment of glucose homeostasis is caused by intrinsic, age-dependent dysfunction of islets or by systemic aging factors.Our strategy to discern age-related intrinsic changes in islet function was to study islets from young mature (2 mo) and aged (18 mo) mice and to fol...

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“…2D). Fibrosis is a hallmark of aging in many organs (26,27). We found that blood vessels in islets of aged mice contained more laminin, a biomarker of fibrosis (28) (Fig.…”

Section: Aged Pancreatic Islets Have Inflamed and Fibrotic Blood Vessmentioning

confidence: 88%

Young capillary vessels rejuvenate aged pancreatic islets

Almaça

Molina

Drigo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

116

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“…For example, mis-regulated apoptosis has been implicated in the age-associated increase in fibrotic lung disease in two ways: increased sensitivity to apoptosis in alveolar epithelial cells may lead to greater injury, whereas reduced sensitivity to apoptosis in fibroblasts and myofibroblasts may promote fibrosis (Kapetanaki et al, 2013). …”

Section: Pcd In Normal Tissue Development Adult Homeostasisand Agingmentioning

confidence: 99%

Programmed cell death in aging

Tower

2015

Ageing Research Reviews

331

208

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Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are required for normal cell turnover and tissue homeostasis. Mis-regulation of PCD is increasingly implicated in aging and aging-related disease. During aging the cell turnover rate declines for several highly-mitotic tissues. Aging-associated disruptions in systemic and inter-cell signaling combined with cell-autonomous damage and mitochondrial malfunction result in increased PCD in some cell types, and decreased PCD in other cell types. Increased PCD during aging is implicated in immune system decline, skeletal muscle wasting (sarcopenia), loss of cells in the heart, and neurodegenerative disease. In contrast, cancer cells and senescent cells are resistant to PCD, enabling them to increase in abundance during aging. PCD pathways limit life span in fungi, but whether PCD pathways normally limit adult metazoan life span is not yet clear. PCD is regulated by a balance of negative and positive factors, including the mitochondria, which are particularly subject to aging-associated malfunction.

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“…Histopathological studies have demonstrated that modifications in extracellular matrix might contribute to the physiological decline in lung function; essentially, fibronectin expression increases with excessive deposition of collagen proteins, whereas the content of elastin fibers is decreased; the result is an enlargement of the distal airspace and abnormal tissue remodeling [3]. …”

Section: Purposementioning

confidence: 99%

The Senile Lung as a Possible Source of Pitfalls on Chest Ultrasonography and Computed Tomography

Ciccarese¹,

Chiesa²,

Feletti

et al. 2015

Respiration

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Background: Age-associated changes in the pulmonary system could be detected with imaging techniques. Widespread use of lung ultrasonography (US) requires characterization of a normal pattern. Objectives: To compare US and computed tomography (CT) findings in healthy subjects undergoing both techniques (with CT as the gold standard). Methods: We prospectively selected 59 subjects undergoing chest CT and US on the same day, without a history of smoking, respiratory symptoms, or known pulmonary pathologies. There were 44 patients in group 1 (age =60 years - elderly) and 15 patients in group 2 (age =50 years - young). Lung US was performed with a convex and a linear probe, and 10 chest areas per patient were analyzed. Convex and linear probe agreement was evaluated by means of the Cohen κ statistic; Fisher's exact test was used to compare categorical variables between groups. Results: Isolated B-lines were frequent in both group 1 (54.5%) and group 2 (40.0%); the number of chest areas positive for B-lines increased with age (16.1% in group 1 vs. 5.3% in group 2, p = 0.0028). In group 2, we found that 37.5% of subjects with B-lines had at least 1 chest area with multiple B-lines, but only 2 subjects had 2 or more. Moreover, in group 1 the chest CT documented a reticular pattern (2.3%), areas of increased density (9.1%), ground glass (6.8%), cysts (2.3%), bronchiectasis (22.7%), and bronchial thickening (6.8%); in group 2, only cysts (6.7%) and bronchiectasis (6.7%) were found. Conclusions: The senile lung is characterized by mild changes on CT and US. Chest areas positive for B-lines increase with age, and focal multiple B-lines can be found. However, diffuse patterns, especially in symptomatic subjects, suggest a different diagnosis.

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Influence of age on wound healing and fibrosis

Cited by 81 publications

References 157 publications

Young capillary vessels rejuvenate aged pancreatic islets

Young capillary vessels rejuvenate aged pancreatic islets

Programmed cell death in aging

The Senile Lung as a Possible Source of Pitfalls on Chest Ultrasonography and Computed Tomography

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