How RNA Polymerase Holds the Key to Reverse Aging! 🕰️✨ Dive into the Groundbreaking Findings Now!

The Role of RNA Polymerase in Reverse Aging

In an innovative study, scientists from the University of Cologne in Germany examined the complex realm of aging in different species. They found that the mechanisms involved are the same in humans, fruit flies, rats, mice, and worms. Their most important discovery, which opens up new avenues for aging effect reversal, is the critical role that RNA polymerase II (RNA pol II) plays in the aging process.

The Aging Transcriptional Landscape:

The researchers observed a consistent pattern across the studied animals – an increase in the speed of transcription with age. This surge in RNA pol II activity, however, came at a cost. The enzyme’s accuracy diminished, leading to a higher incidence of mutations compared to reference genomes. This revelation hinted at a pivotal relationship between transcriptional speed and aging across diverse species.

Nucleosomes and Aging:

The investigation extended to human lung cells and umbilical vein cells, revealing a correlation between aging and the depletion of nucleosomes. Nucleosomes, the tightly compacted structures of DNA and histones, play a vital role in packaging DNA within cells and regulating its accessibility to enzymes like RNA pol II. Increasing histone expression in these cells resulted in a deceleration of RNA pol II, a finding replicated in fruit flies, hinting at a potential key to extending lifespan.

Restoring Balance in Cellular Processes:

As organisms age, physiological homeostasis becomes compromised due to impairments in cellular processes, including transcription and RNA splicing. The study unveiled that the average transcriptional elongation speed, represented by RNA polymerase II speed, increased with age in all five species. Intriguingly, interventions known to extend lifespan, such as dietary restriction and lowered insulin–IGF signaling, reversed most aging-related changes in transcription.

Genetic Variants and Lifespan Extension:

The researchers also identified genetic variants in RNA polymerase II that, when reduced in speed, extended the lifespan of nematodes and fruit flies. Moreover, manipulating the speed of RNA polymerase II by overexpressing histone components countered age-associated changes in nucleosome positioning, extending both the lifespan of flies and the division potential of human cells. These findings offer a glimpse into the fundamental molecular mechanisms governing aging and suggest potential preventive measures.

The University of Cologne study highlights the crucial function of RNA polymerase II and offers a thorough understanding of the aging process in various species. Gaining insight into the complexities of transcriptional modifications and how they affect aging creates new opportunities for creating anti-aging therapies. With continued research into the molecular processes that underlie aging, it may become possible to preserve youthful vitality.

References:

Zhao, S. et al. PiggyBac transposon vectors: the tools of the human gene encoding. Transl Lung Cancer Res.5, 120–125 (2016). [PMC free article] [PubMed]

Adachi K, et al. Esrrb unlocks silenced enhancers for reprogramming to naive pluripotency. Cell Stem Cell. 2018;23:266–275.e6. doi: 10.1016/j.stem.2018.05.020. [PubMed] [CrossRef] [Google Scholar]

Dimri GP, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc. Natl Acad. Sci. USA. 1995;92:9363–9367. doi: 10.1073/pnas.92.20.9363. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Zirkel A, et al. HMGB2 loss upon senescence entry disrupts genomic organization and induces CTCF clustering across cell types. Mol. Cell. 2018;70:730–744.e6. doi: 10.1016/j.molcel.2018.03.030. [PubMed] [CrossRef] [Google Scholar]

Berridge MV, Tan AS. Characterization of the cellular reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT): subcellular localization, substrate dependence, and involvement of mitochondrial electron transport in MTT reduction. Arch. Biochem. Biophys. 1993;303:474–482. doi: 10.1006/abbi.1993.1311. [PubMed] [CrossRef] [Google Scholar]

Sepp KJ, Schulte J, Auld VJ. Peripheral glia direct axon guidance across the CNS/PNS transition zone. Dev. Biol. 2001;238:47–63. doi: 10.1006/dbio.2001.0411. [PubMed] [CrossRef] [Google Scholar]

Share on Facebook

Tweet