Molecular hallmarks of long non-coding RNAs in aging and its significant effect on aging-associated diseases

Abstract

Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes (e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA- and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.

The hallmarks of aging as a conceptual framework for health and longevity research

“…Another candidate hallmark supported by several studies is the dysregulation of RNA processing, a process that regulates gene expression ( Figure 4 ). This hallmark was first proposed in the Copenhagen aging meeting in 2022 ( Schmauck-Medina et al, 2022 ) and then supported by other studies that highlighted the relevance of long non-coding RNAs ( Sherazi et al, 2023 ) and RNA binding proteins ( Varesi et al, 2023 ) in the aging process. These works pointed out that these elements lose their regulation during aging and how the subsequent molecular and cellular changes promote the aging process and its associated diseases ( Sherazi et al, 2023 ; Varesi et al, 2023 ).…”

Regulatory RNAs in immunosenescence

“…124 Therefore, lncRNAs may affect several cellular processes, including cellular proliferation, differentiation, senescence, quiescence, and response to stress and immune agents. 125…”

“…LncRNAs are expressed during cell differentiation and development which makes them capable of regulating the cell cycle, DNA replication timing and chromosome stability, genetic imprinting, stem cell reprogramming, chromatin remodeling, gene transcription, mRNA stability, translation, and protein stability 124 . Therefore, lncRNAs may affect several cellular processes, including cellular proliferation, differentiation, senescence, quiescence, and response to stress and immune agents 125 …”

Neuronal dysfunction and gene modulation by non-coding RNA in Parkinson’s disease and synucleinopathies

“…In recent years, lncRNAs were particularly studied for their role in the regulation of transcription and translation in physiological conditions and disease. Since lncRNA are particularly expressed and conserved in the brain (Ponjavic et al, 2009;Chodroff et al, 2010;Barry, 2014;Yang et al, 2021;Kyzar et al, 2022), their role was investigated in the epigenetic adaption of gene expression in drug addiction, aging, neuroinflammation, brain injury, neurodegenerative and neurodevelopmental diseases (Wang et al, 2018;Srivastava et al, 2021;Sivagurunathan et al, 2022;Yang K. et al, 2022;Mazzeo et al, 2023;Ruffo et al, 2023;Sherazi et al, 2023). The expression rate of lncRNAs is epigenetically modulated.…”