Basics of cellular aging and

Editor's Notes

• #7: SDH=Succinate dehydrogenase  AC Pase=Acid phosphatase 
• #20: Approximately 90% of individuals presenting Werner syndrome have any of a range of mutations in the gene, WRN, the only gene currently attributed to cause Werner syndrome.[11][12] WRN, which lies on chromosome 8 in humans,[23] encodes the WRNp protein, a 1432 amino acid protein with a central domain resembling members of the RecQhelicases. RecQ helicases are a special type of helicase that function at unique times during DNA repair of doubled Werner syndrome (WS), also known as "adult progeria",[1] is a rare, autosomal recessive disorder[2] which is characterized by the appearance of premature aging stranded breaks, which are a form of DNA damage that results in a break of both strands of DNA. Thus, RecQ helicases are important for maintaining DNA stability, and loss of function of these helicases has important implications in the development of Werner syndrome.
• #21: Spindle checkpoint From Wikipedia, the free encyclopedia Jump to navigationJump to searchDuring the process of cell division, the spindle checkpoint prevents separation of the duplicated chromosomes until each chromosome is properly attached to the spindle apparatus. In order to preserve the cell's identity and proper function, it is necessary to maintain the appropriate number of chromosomes after each cell division. An error in generating daughter cells with fewer or greater number of chromosomes than expected (a situation termed aneuploidy), may lead in best case to cell death, or alternatively it may generate catastrophic phenotypic results.[1] Examples include: In cancer cells, aneuploidy is a frequent event, indicating that these cells present a defect in the machinery involved in chromosome segregation, as well as in the mechanism ensuring that segregation is correctly performed. In humans, Down syndrome appears in children carrying in their cells one extra copy of chromosome 21, as a result of a defect in chromosome segregation during meiosis in one of the progenitors. This defect will generate a gamete (spermatozoide or oocyte) with an extra chromosome 21. After fertilisation, this gamete will generate an embryo with three copies of chromosome 21. The mechanisms verifying that all the requirements to pass to the next phase in the cell cycle have been fulfilled are called checkpoints. All along the cell cycle, there are different checkpoints. The checkpoint ensuring that chromosome segregation is correct is termed spindle assembly checkpoint (SAC), spindle checkpoint or mitotic checkpoint. During mitosis or meiosis, the spindle checkpoint prevents anaphase onset until all chromosomes are properly attached to the spindle. To achieve proper segregation, the two kinetochoreson the sister chromatids must be attached to opposite spindle poles (bipolar orientation).[2] Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. An adduct (from the Latin adductus, "drawn toward" alternatively, a contraction of "addition product") is a product of a direct addition of two or more distinct molecules, resulting in a single reaction product containing all atoms of all components.[1] The resultant is considered a distinct molecular species. Examples include the addition of sodium bisulfite to an aldehyde to give a sulfonate. It can just be considered as a single product resulting from direct addition of different molecules and constitutes all the reactant molecules' atoms.
• #28: DNA methylation is a process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts to repress gene transcription. [preventingtranscription of the genes into messenger RNA]
• #29: histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes.[1][2] They are the chief protein components of chromatin, acting as spools around which DNA winds, and playing a role in gene regulation. Without histones, the unwound DNA in chromosomes would be very long (a length to width ratio of more than 10 million to 1 in human DNA). For example, each human diploid cell (containing 23 pairs of chromosomes) has about 1.8 meters of DNA; wound on the histones, the diploid cell has about 90 micrometers (0.09 mm) of chromatin. When the diploid cells are duplicated and condensed during mitosis, the result is about 120 micrometers of chromosomes.[3]
• #31: Endogenous and exogenous stress causes the unfolding of proteins (or impairs proper folding during protein synthesis). Unfolded proteins are usually refolded by heat-shock proteins (HSP) or are targeted to destruction by the ubiquitin-proteasome or lysosomal (autophagic) pathways. The autophagic pathways include recognition of unfolded proteins by the chaperone Hsc70 and their subsequent import into lysosomes (chaperone-mediated autophagy) or sequestration of damaged proteins and organelles in autophagosomes that later fuse with lysosomes (macroautophagy). Failure to refold or degrade unfolded proteins can lead to their accumulation and aggregation, resulting in proteotoxic effects.
• #36: The bystander effect, or bystander apathy, is a social psychological phenomenon in which individuals are less likely to offer help to a victim when other people are present.
• #37: The proposed nine hallmarks of aging are grouped into three categories. (Top) Those hallmarks considered to be the primary causes of cellular damage. (Middle) Those considered to be part of compensatory or antagonistic responses to the damage. These responses initially mitigate the damage, but eventually, if chronic or exacerbated, they become deleterious themselves. (Bottom) Integrative hallmarks that are the end result of the previous two groups of hallmarks and are ultimately responsible for the functional decline associated with aging.
• #38: 5' AMP-activated protein kinase or AMPK or 5' adenosine monophosphate-activated protein kinase is an enzyme (EC 2.7.11.31) that plays a role in cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low. It belongs to a highly conserved eukaryotic protein family and its orthologues are SNF1 and SnRK1 in yeast and plants, respectively. The mammalian target of rapamycin (mTOR), also known as the mechanistic target of rapamycin and FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the MTOR gene.[5][6][7]mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases The sirtuins (SIRT1–7) are a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacylases with remarkable abilities to prevent diseases and even reverse aspects of ageing. Mice engineered to express additional copies of SIRT1 or SIRT6, or treated with sirtuin-activating compounds (STACs) such as resveratrol and SRT2104 or with NAD+ precursors, have improved organ function, physical endurance, disease resistance and longevity. Trials in non-human primates and in humans have indicated that STACs may be safe and effective in treating inflammatory and metabolic disorders, among others. These advances have demonstrated that it is possible to rationally design molecules that can alleviate multiple diseases and possibly extend lifespan in humans. Mitophagy is the selective degradation of mitochondria by autophagy. Low-level oxidative stress induces an adaptive response commonly defined as hormesis; this type of stress is often related to reactive oxygen species (ROS) originating from the mitochondrial respiratory chain (mitochondrial hormesis ormitohormesis).