Senescence 2

Time-lapse imaging

Recording of cell division over time

HEK293

Cell line used in the experiment

Dox:GFP-tau

Fluorescent protein expressed in the cells

Isoform 0N4R

Specific variant of the tau protein

Cells imaged every 10 min

Frequency of imaging during the experiment

15 hr

Duration of the imaging experiment

MTOC

Microtubule organizing center

Progression of the cell cycle

Advancement through different stages of cell division

Molecular interactions

Chemical reactions between molecules

CDK

Cyclin-dependent kinase

Inactivated form

State of CDK when not active

Cyc

Cyclin binding to CDK

Promote entry into the cell cycle

Facilitate the start of cell division

p16, p21, p27

CDK inhibitors

E2F

Transcription factor involved in cell cycle regulation

RB

Tumor suppressor retinoblastoma

CCN

Cyclin protein

CDC

Cell division cycle protein

CDT1

Chromatin licensing and DNA replication factor 1

MAD2L1

Mitotic arrest deficient-like 1 protein

MCM

Minichromosome maintenance complex component

PLK1

Polo-like kinase 1

Senescence pathway

Process leading to cellular senescence

Physiological conditions

Normal biological processes

Ageing processes

Natural aging of cells and organisms

Pathological stresses

Abnormal or harmful conditions

Age-related changes

Alterations that occur with aging

Chemotherapy

Treatment of disease with drugs

Radiation

Emission of energy in the form of waves or particles

Genomic DNA damage

Injury to the DNA sequence

Telomere shortening

Reduction in the length of telomeres

Consequence of DNA damage

Result or effect of DNA damage

Cellular senescence

State of permanent cell cycle arrest

Persistence

Continuation or lasting presence

DD

DNA damage

DDR

DNA damage response

SASP

Senescence-associated secretory phenotype

Impair stem cell properties

Reduce the function of stem cells

Alter differentiation

Change the process of cell specialization

DNA repair mechanisms

Processes that fix DNA damage

Cell cycle arrest

Halting of cell division

Regulated cell death

Controlled cell demise

Cancer

Disease characterized by uncontrolled cell growth

Replicative stress

Pressure on the DNA replication process

Telomere attrition

Gradual erosion of telomeres

DNA replication

Copying of DNA molecules

Replication fork

Site where DNA replication occurs

RNA primers

Short RNA sequences used to initiate DNA synthesis

Unwinds

Separates the DNA double helix

Coat

Protective layer or covering

Discontinuously

In a non-continuous manner

Seals

Closes or secures

DNA shortening

Reduction in the length of DNA molecules

Telomere

Short nucleotide sequences at the ends of chromosomes

Hexameric sequence TTAGGG

Repeating DNA pattern found in telomeres

Lagging strand

DNA strand synthesized in short fragments

Telomerase

Enzyme that adds telomere repeats to chromosome ends

Human leukocyte telomere length (LTL)

Measurement of telomere length in white blood cells

Telomere damage

Injury to telomeres

Proliferating tissues

Tissues with active cell division

DDR activation

Response to DNA damage

Molecular pathways of senescence

Biochemical processes leading to senescence

Multiple stressors

Various factors that induce stress

Damaging agents

Substances that cause harm or damage

Epigenetic modifications

Changes in gene expression without altering the DNA sequence

DNA methylation

Addition of a methyl group to DNA

Non-coding RNA

RNA molecules that do not code for proteins

Histone modification

Chemical changes to histone proteins

Cellular senescence

State of permanent cell cycle arrest

Neurodegenerative disorders

Conditions that cause progressive loss of brain function

Proteostasis network

System that maintains protein homeostasis

Molecular chaperones

Proteins that assist in protein folding

Proteolytic machinery

Enzymes that degrade proteins

Proteome

Complete set of proteins in a cell

Histones

Proteins that package DNA

Cytoskeletal proteins

Proteins that provide structural support to cells

Ribosomal proteins

Proteins that make up ribosomes

Proteostasis

Maintenance of protein balance

Senescence is a complex cell fate

Senescence involves multiple cellular processes

Acute senescent cells

Senescent cells with short-term effects

Kinetics of senescence induction

Rate at which senescence occurs

Wound healing

Process of repairing damaged tissue

Tissue repair

Restoration of damaged tissue

Embryonic development

Growth and differentiation of an embryo

Scheduled clearance

Planned removal of cells

Oncogene-induced senescence

Senescence triggered by oncogenes

Chronic senescence

Senescence with long-term effects

Cellular stress

Pressure on cells due to various factors

Macromolecular damage

Injury to large molecules in cells

Post-mitotic tissues

Tissues that no longer undergo cell division

Irreparable DNA damage

DNA damage that cannot be repaired

Persistent DDR activation

Continued response to DNA damage

Arrested proliferation

Halting of cell growth

SASP activation

Induction of senescence-associated secretory phenotype

Unified model of senescence

Comprehensive explanation of senescence

Tissue remodeling

Reorganization of tissues

Stem cell aging

Decline in function of stem cells with age

Stem cell number

Quantity of stem cells in an organism

Self-renewal

Ability of stem cells to produce more stem cells

Fates of damaged stem cells

Outcomes of stem cells with DNA damage