Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging

Grammatikakis, Ioannis; Panda, Amaresh C.; Abdelmohsen, Kotb; Gorospe, Myriam

doi:10.18632/aging.100710

Cited by 185 publications

(127 citation statements)

References 191 publications

(206 reference statements)

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“…For example, long non-coding RNAs (lncRNAs) such as XIST and HOTAIR promote gene silencing through interactions with chromatin-modifying enzymes (Rinn and Chang, 2012). These regulatory RNAs are emerging as important players in the progression of aging (Grammatikakis et al, 2014). One interesting example of an lncRNA that is associated with aging is the H19 lncRNA.…”

Section: The Aging Epigenomic Regulatory Landscapementioning

confidence: 99%

The Aging Epigenome

2016

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During aging, the mechanisms that normally maintain health and stress resistance strikingly decline, resulting in decrepitude, frailty, and ultimately death. Exactly when and how this decline occurs is unknown. Changes in transcriptional networks and chromatin state lie at the heart of age-dependent decline. These epigenomic changes are not only observed during aging but also profoundly affect cellular function and stress resistance, thereby contributing to the progression of aging. We propose that the dysregulation of transcriptional and chromatin networks is a crucial component of aging. Understanding age-dependent epigenomic changes will yield key insights into how aging begins and progresses and should lead to the development of new therapeutics that delay or even reverse aging and age-related diseases.

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Section: The Aging Epigenomic Regulatory Landscapementioning

confidence: 99%

The Aging Epigenome

2016

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“…The notion of lncRNAs (over 200 bp in length) is still young (48), but they are the subject of an emerging body of work to uncover their role in aging and pathological processes (49). It is hypothesized that they can function as competing endogenous miRNAs (ceRNA).…”

Section: Cellular Perturbations In the Ipf Lungmentioning

confidence: 99%

Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

Mora¹,

Bueno²,

Rojas³

2017

Journal of Clinical Investigation

170

158

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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...

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“…Recent reports indicate that lncRNAs are critical regulators of physiological processes such as cell division and differentiation, and numerous human diseases including cancer and neurodegeneration [76–78]. Recently, we screened for senescence-associated lncRNAs in human diploid fibroblasts and found that the expression of several lncRNAs was altered in senescent cells [79, 80]. In this section, we will discuss the role of lncRNAs in SASP.…”

Section: Long-noncoding Rnas (Lncrnas)mentioning

confidence: 99%

SASP regulation by noncoding RNA

Panda

Abdelmohsen

Gorospe

2017

Mechanisms of Ageing and Development

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Noncoding RNAs (ncRNAs), including micro (mi)RNAs, long noncoding (lnc)RNAs, and circular (circ)RNAs, control specific gene expression programs by regulating transcriptional, post-transcriptional, and post-translational processes. Through their broad influence on protein expression and function, ncRNAs have been implicated in virtually all cellular processes such as proliferation, senescence, quiescence, differentiation, apoptosis, and the stress and immune responses. Senescence is a cellular phenotype associated with the physiologic decline of aging and with age-related pathologies. Besides their characteristic terminal growth arrest and differential gene expression programs, senescent cells are known to secrete potent pro-inflammatory, angiogenic, and tissue-remodeling factors. This important trait, known as the senescence-associated secretory phenotype (SASP), influences many biological processes such as tissue repair and regeneration, tumorigenesis, and the aging-associated pro-inflammatory state. Here, we review the microRNAs, lncRNAs, and circRNAs that influence the production of SASP factors and discuss the rising interest in SASP-regulatory ncRNAs as diagnostic and therapeutic targets.

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Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging

Cited by 185 publications

References 191 publications

The Aging Epigenome

The Aging Epigenome

Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis

SASP regulation by noncoding RNA

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