Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

Abstract

One of the most remarkable medical accomplishments in the last century has been the increasing longevity of the human population. A decrease in birth rates, accompanied by a reduction in mortality among the elderly population, has collectively increased the percentage of the aged population, particularly in developed countries. Globally, it is estimated that the proportion of the population over the age of 60 will increase from 11% to 22% by 2050, and 28% by 2100. Currently, 18% of the US population is over 60 years of age (57 million), which is predicted to rise to 27% (107 million) in 2050 and up to 31% (149 million) by 2100 (1). The aging population has propelled an increase in the overall prevalence of chronic conditions. Several lung diseases, including acute lung injury and asthma, and some infectious diseases, such as pneumonia, increase in severity and mortality with age. Additionally, there has been a significant increase in incidence of chronic lung diseases -including chronic obstructive pulmonary disease, most forms of lung cancer, and idiopathic pulmonary fibrosis (IPF) -resulting in aging-related increases in prevalence.IPF is the most common form of idiopathic interstitial lung diseases. Its overall incidence in the US is 7 to 17 per 100,000 persons with a prevalence between 13.2 and 63 per 100,000 persons (2). A 1996 study initially demonstrated a higher incidence and prevalence of IPF in patients over 65 (3). These observations were confirmed more recently by Raghu et al. (4) and others, using both broad and narrow case-finding criteria for IPF diagnosis. These studies estimated that in the US, the prevalence of IPF increases with age, ranging from 4 per 100,000 for population aged between 18 and 34 years old to 227.2 per 100,000 among those 75 or older (4). This aging-related increase in cumulative incidence and prevalence of IPF has been corroborated by several studies that include populations in Europe and Asia (5-9). Accordingly, the median age at diagnosis of sporadic IPF ranges between 50 and 85 years old, and patients younger than 50 are more commonly associated with familial, rather than sporadic, forms of the disease (2). Mortality rates from IPF are steadily increasing worldwide, and a positive association has also been observed with advanced age (10). Examination of US government health insurance data for people aged 65 and older shows an increasing prevalence of IPF among older age groups (11). These studies confirm the growing concern that aging, and consequently age-related diseases, will drive up health care expenditures. As the elderly population in developed countries is expected to double in the next 25 years, there is an urgent need to understand the pathogenesis of IPF and develop interventions to attenuate or reverse lung fibrosis. The physiology of aging and the lungEvolutionary theories of aging include the concept of selection shadow that permits the accumulation of mutations with late deleterious effects, and the theory of antagonistic pleiotropy, which supports the sele...

Reducing protein oxidation reverses lung fibrosis

“…Our previous work showing that Fas-SSG occurred in association with ER-redox perturbations 38 point to a potential role of ER-linked oxidative processes in pulmonary fibrosis 31 . Additionally, dysregulation of mitochondrial homeostasis, and associated increases in ROS, have been implicated in pulmonary fibrosis 39,40 . PSSG observed herein could be a potential consequence of NOX4- or mitochondrially-derived oxidants, although additional studies will be required to address these possibilities.…”

Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic inflammatory diseases

“…Pulmonary fibrosis, a disease associated with aging, has been shown to have altered mitochondria (reviewed in (Mora et al, 2017)). Dysfunctional mitochondria in alveolar epithelial cells in IPF has been linked to reduced expression of PINK1 (a regulator of mitochondrial homeostasis) (Bueno et al, 2015; Patel et al, 2015).…”

The indicators of general clinical methods as prognostic markers of the severity of systemic scleroderma complicated by the development of pneumosclerosis.

“…У ряді досліджень з проблеми легеневого пневмосклерозу/фіброзу встановлена роль генетичної схильності [10]. На кращу діагностику пневмосклерозу впливає роз-виток та доступність методів дослідження леге-невої тканини, таких як комп'ютерна томографія (КТ) високої якості, трансторакальні, трансброн-хіальні методи біопсії легень [13].…”