Topic 8 - Key Terms

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activin - A signalling protein that induces cell differentiation of cultured Xenopus mesoderm cells in vitro. (T8P1)

age-specific mortality - A measure of the probability of dying at a particular age (of those who have survived to that age). (T8P3)

aneuploidy - Situation in which a cell contains an abnormal numbers of chromosomes. (T8P4)

animal pole - Pigmented hemisphere of an unfertilised frog oocyte, which (if fertilised) will develop into - the ectoderm and mesoderm of the embryo. (T8P1)

antagonistic pleiotropy theory - An ultimate (evolutionary) theory of ageing that posits that any mutations that confer advantages during early, reproductive life will be selected for, even if they confer disadvantages in post-reproductive life. Such mutations would be likely to occur in different populations/species. (T8P3)

biological ageing - Biological ageing refers to changes that occur with increasing chronological age and are deleterious (reduce or disrupt normal function), progressive (take place gradually), intrinsic (not a result of a modifiable environmental change) and universal (occur in all members of a species). See also senescence. (T8P3)

blastopore - A hole formed at the dorsal end of the blastula that secretes TGF-β family molecules; important for nervous system development. (T8P1)

blastula - The ball of cells that is formed as a result of the cleavage divisions of the zygote. (T8P1)The ball of cells that is formed as a result of the cleavage divisions of the zygote. (T8P1)

body plan - The basic shape of members of an animal phylum, assumed as an organism develops; includes features such as head-to-tail arrangement, any symmetry or segmentation, and the arrangement of any limbs. (T8P1)

caloric restriction - Provision of a reduced amount of food. The restriction is in calorific value; essential nutrients are still provided. Sometimes also called dietary restriction. (T8P3)

cellular senescence - Phenotypic changes observed in both replicatively senescent cells and also in non-dividing cells (e.g. neurons) in ageing animals. See also senescence-associated secretory phenotype (SASP). (T8P5)

cleavage - The first, rapid mitotic cell divisions that the zygotes of most animals undergo. No cell growth occurs between cleavage divisions, and a clump of smaller cells known as blastula is formed. (D. melanogaster is a notable exception, in that a syncytial blastoderm is formed.) (T8P1)

Cockayne syndrome - A segmental progeroid syndrome in which there is a defect in nucleotide excision repair. (T8P4)

colinearity - The observation that the 3′ to 5′ order in which Hox genes are located along their chromosomes mirrors the anterior–posterior order in which they are expressed in the body (T8P2).

cortical rotation - The movement of cytoplasm within the oocyte, induced by fertilisation. (T8P1)

daf genes - Genes that are involved in dauer formation in C. elegans. Mutations in some of the daf genes have also been found to increase both lifespan and stress resistance of adult worms. Homologous genes have similar role in other model organisms. (T8P5)

development - All the changes that take place during the formation of a mature organism from a zygote. (T8P1)

disposable soma theory - An ultimate (evolutionary) theory of ageing that posits that mutations that benefit the germ line, rather than the rest of the body (somatic cells), will be selected for. (T8P3)

DNA damage response (DDR) - A cellular response generated by telomere shortening, and DNA damage. The DDR involves upregulation of some signalling pathways, including activation of p38 MAP kinase (p38 MAPK), resulting in development of a secretory and pro-inflammatory phenotype (the SASP), which results in growth arrest, removal of damaged cells and an ageing phenotype. (T8P5)

Eph - Family of ephrin receptor tyrosine kinases, regulating cell–cell interactions such as cell migration, formation of tissue boundaries, and segmentation. (T8P2)

ephrin - Proteins (usually expressed on the cell surface) that interact with Eph receptors and play a variety of roles in development, such as cell migration, formation of tissue boundaries, and segmentation. For example, they are involved in preventing cells of the developing hindbrain moving from one rhombomere to another. (T8P2)

Free radicals - Atoms or molecules that possess unpaired electrons and so have the potential to cause molecular damage. (T8P4)

free radical theory of ageing - This proximate theory of ageing posits that ageing occurs as a result of damage to molecules, organelles and cells caused by free radicals (generated by oxidative metabolism and some other cellular processes). (T8P4)

germ layers - The three major regions of the embryo (ectoderm, endoderm, and mesoderm) that will develop in different tissues in the adult. (T8P1)

homeotic transformations - Changes in the identity of an entire body segment, such as transforming a leg-bearing segment into a wing-bearing segment. (T8P2)

Hox genes - A class of transcription factor-encoding genes important for specifying positional identity along the anterior–posterior axis. (T8P2)

induction - A change in the properties of a group of cells that occurs as a result of signals from a nearby group of cells. (T8P1)

INK4a/ARF locus - A locus that encodes two proteins, p16INK4 and p19ARF, which have important roles as tumour suppressors, but which also induce cell senescence. (T8P5)

in situ hybridisation (ISH) - The technique of revealing the presence of specific mRNAs within fixed tissue or cell samples, by using complementary sequences that are attached to a fluorescent dye or enzyme reporter (T8P1).

insulin/IGF1 pathway - A highly conserved signalling pathway that is activated by insulin and/or IGF1 in response to high nutrient levels. Reduced activity of this pathway leads to increased longevity and increased stress resistance. Sometimes also called the IIS pathway. (T8P5)

life history - Characteristic traits of species that include age at first reproduction, frequency of reproduction, the number and size of offspring, the extent of parental care given, and the investment of an organism in its own survival. (T8P3)

lifespan - The length of an organism’s life. See also longevity. (T8P3)

lipofuscin - An autofluorescent pigment formed by the incomplete breakdown of the fused autophagosome and lysosome. It appears as a mixture of electron-dense and paler structures under EM. Accumulation of lipofuscin often occurs in cells during ageing. (T8P4)

longevity - Length of life. (T8P3)

mitochondrial free radical theory of ageing - This proximate theory of ageing posits that free radical generation by mitochondria increases with increasing age, causing molecular, organelle and ultimately cellular damage that results in ageing. (T8P4)

morphogenesis - Changes in form that occur during development. (T8P1)

morphogen gradients - Gradients of secreted protein that play a role in morphogenesis because the response generated in cells is dependent upon the concentration of morphogen protein that the cell is exposed to. (T8P1)

mutation accumulation theory - An ultimate (evolutionary) theory of ageing that posits that any mutations that affect an individual after reproductive age will not be selected against, so can accumulate in a population. Such mutations would be predicted to be random. (T8P3)

‘network’ theory of ageing - A mechanistic proximate theory of ageing that posits that multiple mutations or damage have resulted in many changes (effectively a network of changes) that cause biological ageing. (T8P3)

neural induction - Specification of part of the ectoderm into neuroectoderm. (T8P1)

neural plate - A sheet of cells (part of the neuroectoderm) with epithelial properties that will give rise to the cells of the neural tube. (T8P1)

NeuroD - Downstream target of neurogenin responsible for establishing neuronal cell fates and suppressing glial cell fates. (T8P1)

neuroectoderm - The part of the ectoderm that will become neural tissue. (T8P1)

neurogenin - Transcription factor that acts on NeuroD to promote neural cell fates and to suppress glial cell fates. (T8P1)

neurulation - The developmental stage during which the neural plate invaginates and rolls into a tube to form the neural tube; the forerunner of the spinal cord and brain. (T8P2)

nitric oxide (NO) - A soluble gaseous free radical that acts as a signalling molecule in many animal species (and in some bacteria). It is formed by the action of the enzyme nitric oxide synthase (NOS). In mammals NO is used for intercellular signalling by neurons and vascular endothelial cells. (T8P6)

Noggin - Protein secreted from the organiser. It inhibits differentiation of ectodermal cells into epidermal cells and therefore promotes differentiation of neuroectoderm. (T8P1)

nuclear lamin proteins - Specific cytoskeletal proteins in the nuclear lamina that are essential for the maintenance of nuclear structure and for anchoring chromatin and nuclear pores. These proteins are of the intermediate filament type. (T8P4)

nutrient-sensing pathway - Signalling pathways that are activated by high or low levels of nutrients. Activation of these pathways affect lifespan and stress resistance. (T8P5)

organiser - Area of the dorsal lip region of the amphibian blastomere that produces signalling molecules that direct the later differentiation and hence development of different tissues of the embryo. Similar regions exist in other vertebrates. (T8P1)

oxidative damage - Molecular changes in molecules caused by free radicals. These can be structural and or chemical changes. (T8P4)

oxidative stress - The situation in which the levels of free radicals are elevated, and molecular damage occurs as a result. (T8P4)

population doubling (PD) - The number of times the total population of replicative cells in a culture has doubled before cell division ceases. (T8P5)

progeroid syndromes - Human disorders in which premature ageing occurs. There are two types of progeroid syndrome:

unimodal, in which only one type of tissue is affected (e.g. familial Alzheimer’s disease and Parkinson’s disease)

segmental, in which several tissues are affected (e.g. Werner syndrome and Cockayne syndrome).

(T8P4)

proteostasis - The maintenance (or homeostasis) of levels and folding of proteins in the cell. (T8P4)

proximate theories of ageing - Theories that aim to explain how ageing occurs, i.e. the molecular, cellular and physiological changes that take place in organisms as they get older and which result in ageing. (T8P3)

rapamycin - A drug with antifungal and immunosuppressant properties that is used as a post-transplantation therapy and in the treatment of some cancers. There is evidence that rapamycin enhances longevity in some model organisms (including mice, C. elegans, Drosophila and S. cerevisiae) through its inhibitory actions on the PI 3-kinase mTOR. (T8P5)

Rb (retinoblastoma) - A tumour-suppressor protein encoded by the Rb gene. The Rb protein ensures that cell division does not proceed until conditions are appropriate. In its unphosphorylated state, Rb acts as a brake on the cell cycle by binding to the transcription factors needed for the expression of the molecular machinery for cell proliferation, including those required for DNA replication. When Rb is phosphorylated (by G1 cyclin-Cdks), it releases the transcription factors and the cell can progress through the cell cycle. (T8P5)

reactive nitrogen species (RNS) - Free radicals and non-radical oxidants that are derived from nitrogen-based molecules. Note that some free radicals (such as nitric oxide) and non-radical oxidants (such as peroxynitrite) can be considered as both RNS and reactive oxygen species (ROS). (T8P4)

replicative senescence - The state at which the ability of a mitotic cell to divide ceases. Replicative senescence was first observed during analysis of mitotic cells in culture, which were found to have a finite ability to divide. (T8P5)

rhombomeres - Distinct regions in the developing hindbrain. The cells in different rhombomeres go on to differentiate into neurons that will innervate different targets (such as different muscles of the face). (T8P2)

segmentation - The subdivision of an organism during development into multiple blocks of cells that may acquire specialised functions. (T8P1)

segmentation clock - The synchronised molecular feedback loops within groups of cells that regulate the timing of segment formation during development. (T8P2)

senescence - A term that is often used as an alternative to biological ageing, because the term ‘ageing’ does not discriminate between chronological and biological ageing. When used together with other terms it can have a specific meaning (e.g. replicative senescence). See also biological ageing. (T8P3)

senescence-associated secretory phenotype (SASP) - The secretory and pro-inflammatory phenotype exhibited by senescent cells (both replicative and non-replicative cell types). The SASP includes production and secretion of a range of molecules that can affect nearby cells and tissues. (T8P5)

sirtuin - A family of NAD-dependent protein deacetylases with a range of roles and actions that are implicated in ageing. (T8P4)

somites - Paired segmented structures formed as a result of changes along the anterior–posterior axis of the mesoderm, which give rise to the vertebrae, muscles and other tissues. (T8P2)

survival curve - A graph showing the number of individuals in a population that are surviving plotted against age. This can also be described as a graph showing when individuals in a population die; i.e. their lifespan or longevity. (T8P3)

tissues - Groups of cells that together perform a specific function or functions, but which may sometimes contain different cell types. (T8P1)

ultimate theories of ageing - Theories that aim to explain why ageing occurs, i.e. why it has evolved. (T8P3)

vegetal pole - Non-pigmented hemisphere of an unfertilised frog oocyte, which (if fertilised) will develop into the endoderm of the embryo. (T8P1)

VegT - A maternally provided transcription factor, expressed in cells in the vegetal pole. It induces the expression of Xnr genes, which along with another transcription factor, β-catenin, establishes a gradient of Xnr-related proteins along the dorsal–ventral axis. (T8P1)

Werner syndrome - A segmental progeroid syndrome in which the WRN gene, which encodes an enzyme of the RecQ helicase family, is defective. (T8P4)

xenobiotics - Foreign molecules to which an organism is exposed. These do not include extrinsic molecules (e.g. nutrients) that are normally present in an organism. (T8P4)

Xenopus nodal-related (Xnr) genes - A family of zygotic genes that encode proteins belonging to the TGF-β (transforming growth factor β) family, responsible for formation of mesendoderm (the common precursor of mesoderm and endoderm) in the frog blastula. (T8P1)

β-catenin - A multi-functional signalling molecule, involved in cell-cell adhesion via E-cadherin, and in transcriptional control via TCF/LEF. The amount of β-catenin is regulated by its synthesis and by a destruction complex and this balance tightly controls its activity. (T8P1)