Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for “inflamm‐aging”

Pinti, Marcello; Cevenini, Elisa; Nasi, Milena; Biasi, Sara De; Salvioli, Stefano; Monti, Daniela; Benatti, Simone; Gibellini, Lara; Cotichini, Rodolfo; Stazi, Maria Antonietta; Trenti, Tommaso; Franceschi, Claudio; Cossarizza, Andrea

doi:10.1002/eji.201343921

Cited by 326 publications

(272 citation statements)

References 43 publications

Supporting

Mentioning

247

Contrasting

Order By: Relevance

“…42 Circulating mt-DNA levels increase with age and are positively correlated with the plasma levels of proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and IL-6 in human. 43 In addition, we previously reported that intracellular nondegraded mt-DNA induces the innate immune response leading to inflammation via TLR9-dependent signaling in mouse hearts. 44 Thus, it is possible that the increased, undigested mt-DNA associated with aging is involved in SASP development in an autonomous manner.…”

Section: Inflammaging and Senescence-associated Secretory Phenotypementioning

confidence: 99%

Macromolecular Degradation Systems and Cardiovascular Aging

Nakayama

Nishida

Otsu³

2016

Circulation Research

View full text Add to dashboard Cite

7Cardiovascular aging or age-associated cardiovascular diseases include atherosclerosis, coronary artery disease, hypertension, heart failure, and atrial fibrillation. In addition, aged hearts are characterized by decreased contractility, impaired diastolic function, and atrium dilatation, indicating that both the functional and the morphological alterations that result in these diseases of the heart occur during the aging process. Abstract: Aging-related cardiovascular diseases are a rapidly increasing problem worldwide. Cardiac aging demonstrates progressive decline of diastolic dysfunction of ventricle and increase in ventricular and arterial stiffness accompanied by increased fibrosis stimulated by angiotensin II and proinflammatory cytokines. Reactive oxygen species and multiple signaling pathways on cellular senescence play major roles in the process. Aging is also associated with an alteration in steady state of macromolecular dynamics including a dysfunction of protein synthesis and degradation. Currently, impaired macromolecular degradation is considered to be closely related to enhanced inflammation and be involved in the process and mechanism of cardiac aging. Herein, we review the role and mechanisms of the degradation system of intracellular macromolecules in the process and pathophysiology of cardiovascular aging.

show abstract

Section: Inflammaging and Senescence-associated Secretory Phenotypementioning

confidence: 99%

Macromolecular Degradation Systems and Cardiovascular Aging

Nakayama

Nishida

Otsu³

2016

Circulation Research

View full text Add to dashboard Cite

show abstract

“…These factors impact mitochondrial function by either promoting the accumulation of mtDNA mutations/deletions, decreased OXPHOS capacity, or excessive mtROS production, which can trigger the release of mitochondria-derived damage-associated molecular patterns (mtDAMPs), such as mtDNA fragments and some mitochondrial proteins [ 169 ]. Progressive impairment of mitochondrial function and integrity and the associated release of immunogenic molecules may thus steadily stimulate the innate immune system and promote infl ammation both systemically and within the brain [ 171 ]. Here, Fig.…”

Section: Mitochondrial Immunogenic Signalsmentioning

confidence: 99%

Mitochondrial Signaling and Neurodegeneration

Picard

McManus

2016

Mitochondrial Dysfunction in Neurodegenerative Disorders

View full text Add to dashboard Cite

The endosymbiosis of mitochondria and the resulting increase in energy supply thus conferred upon the eukaryotic cell enabled the evolution of multicellular organisms and complex organs, such as the brain. As a result, the brain and other organs with high energy demands, depend heavily upon mitochondrial metabolism for normal function, and as a consequence, defects in mitochondrial function lead to neurodegenerative disorders. However, the mechanisms linking mitochondrial defects to hallmarks of neurodegeneration, such as the protein aggregates are also extracellular epigenetic alterations, abnormal gene expression, systemic infl ammation, and protein aggregates, remain unclear.Emerging evidence demonstrates that mitochondria are not only power-generating organelles, but also engage in signaling at multiple levels. During the bioenergetic decline associated with aging, dysfunctional mitochondria generate signals of stress (SOS) that can trigger and/or amplify neurodegenerative processes. In this chapter, we describe emerging mechanisms for mitochondrial signaling at four different levels. Mitochondria communicate (1) with each other via fusion and specialized inter-mitochondrial junctions, (2) with cytoplasmic components via posttranslational modifi cations that shift signaling pathways and promote protein aggregation, (3) with the nucleus to regulate epigenetic modifi cations and gene expression, and (4) with the systemic environment where they alter neuroendocrine and infl ammatory processes that impact neuronal function. The relevance of mitochondrial signaling to neurodegeneration is discussed.

show abstract

“…Both DNA receptors are able to sense microbial DNA during infections as well as endogenous DNA, which may be released upon cell death during aging [21]. In particular, mitochondrial DNA release from damaged mitochondria has been shown to increase with age and thus may drive inflamm-aging [22]. At this point, signaling networks for aging or infections may overlap.…”

Section: Introductionmentioning

confidence: 99%

STING SNP R293Q Is Associated with a Decreased Risk of Aging-Related Diseases

et al. 2018

View full text Add to dashboard Cite

Background: Aging is a multifactorial process driven by several conditions. Among them, inflamm-aging is characterized by chronic low-grade inflammation driving aging-related diseases. The aged immune system is characterized by the senescence-associated secretory phenotype, resulting in the release of proinflammatory cytokines contributing to inflamm-aging. Another possible mechanism resulting in inflamm-aging could be the increased release of danger- associated molecular patterns (DAMPs) by increased cell death in the elderly, leading to a chronic low-grade inflammatory response. Several pattern recognition receptors of the innate immune system are involved in recognition of DAMPs. The DNA-sensing cGAS-STING pathway plays a pivotal role in combating viral and bacterial infections and recognizes DNA released by cell death during the process of aging, which in turn may result in increased inflamm-aging. Objective: The aim of this study was to investigate whether a variation within the STING gene with known impaired function may be associated with protection from aging-related diseases by decreasing the process of inflamm-aging. Methods: STING (Tmem173) R293Q was genotyped in a cohort of 3,397 aged subjects (65–103 years). The distribution of the variant allele in healthy subjects and subjects suffering from aging-associated diseases was compared by logistic regression analysis. Results: We show here that STING 293Q allele carriers were protected from aging-associated diseases (OR = 0.823, p = 0.038). This effect was much stronger in the subgroup of subjects suffering from chronic lung diseases (OR = 0.730, p = 0.009). Conclusion: Our results indicate that decreased sensitivity of the innate immune receptors is associated with healthy aging, most likely due to a decreased process of inflamm-aging.

show abstract

Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for “inflamm‐aging”

Cited by 326 publications

References 43 publications

Macromolecular Degradation Systems and Cardiovascular Aging

Macromolecular Degradation Systems and Cardiovascular Aging

Mitochondrial Signaling and Neurodegeneration

STING SNP R293Q Is Associated with a Decreased Risk of Aging-Related Diseases

Contact Info

Product

Resources

About