Analysis of Aging-Related Nuclear Architecture Alterations

The long-term maintenance of the nuclear architecture is vital for the normal functioning of cells and tissues over a lifetime. Alterations in the function of the nuclear lamina may be drivers of normal aging. It is reported that a conserved DNA damage response induces cumulative changes in chromatin structure and nuclear architecture that are important driving forces behind the inexorable changes that occur in organisms over time.

Fig. 1 Age-related changes in mammalian cell nuclear architecture. (Oberdoerffer P and Sinclair DA, 2011)

Using several imaging technologies for visualizing nuclear architecture, CD BioSciences offers a comprehensive analysis of aging-related nuclear architecture alterations, including nuclear lamina, gene stability, and three-dimensional chromatin organization.

Our Aging-Related Nuclear Architecture Alterations Services

Analyzing nuclear lamina and genome stability

We investigate changes in the composition and organization of the nuclear lamina with aging, focusing on changes in lamina proteins, chromatin interactions, and epigenetic modifications. At the same time, we assess the impact of age-related changes in the nuclear lamina on genome stability, including accumulation of DNA damage, telomere dysfunction, and impaired DNA repair mechanisms.

Analyzing three-dimensional chromatin organization

We help our clients study changes in three-dimensional chromatin structure and nuclear organization with age, by examining changes in chromatin regions, topologically associated domains (TADs), and nuclear localization of genomic loci. Additionally, we explore the impact of age-related changes in chromatin organization on gene expression, DNA accessibility, and cell differentiation processes.

Technical Tools for Analyzing Nuclear Architecture Alterations

Nuclear imaging and tracking technologies

We investigate changes in nuclear dynamics and nuclear structure over time by time-lapse imaging and tracking of fluorescently labeled nuclear components, such as lamellipodial proteins, chromatin, and nuclear pore complex proteins. We also use atomic force microscopy (AFM) for direct visualization and mechanical probing of nuclear structure and nuclear mechanics at the nanoscale, which contributes to a deeper understanding of the nuclear hardness and elasticity changes associated with aging.

Chromosome conformation capture (3C) techniques

We use 3C-based methods (e.g., Hi-C) to investigate spatial interactions between genomic loci, chromatin domains, and nuclear compartments, providing insights into three-dimensional chromatin organization.

Workflow for Analyzing Nuclear Architecture Alterations

• Sample collection, nuclear isolation, and fractionation
  We obtain tissue or cell samples from aged individuals or model organisms representing different stages of aging. We isolate intact nuclei from the collected samples using established nuclear isolation protocols to obtain pure nuclear fractions for subsequent analyses.
• Imaging and visualization of nuclear architecture
  We employ advanced imaging technologies to visualize nuclear structures, nuclear envelope morphology, chromatin organization, and nuclear pore complex architecture. Then, we utilize time-lapse microscopy to observe dynamic changes in nuclear architecture and dynamics during aging.
• Data interpretation
  We interpret the imaging and omics data to identify specific nuclear architecture alterations associated with aging. If requested, we also can assess the functional implications of aging-related nuclear architecture alterations on processes such as gene expression, DNA repair, cellular senescence, and nuclear signaling pathways.

Analyzing nuclear architecture alterations associated with aging is a complex and multifaceted endeavor. CD BioSciences provides analysis of nuclear lamina, genome stability, and chromatin organization, to unravel the mysteries of nuclear architecture alterations driving aging. If you are interested in our services, please feel free to contact us or make an online inquiry.

Reference

1. Oberdoerffer P, Sinclair DA. The role of nuclear architecture in genomic instability and aging. Nat Rev Mol Cell Biol. 2011, 8 (9): 692-702.