by Nick Lane
Soares, M. P., Lin, Y., Anrather, J., et al. Expression of heme oxygenase-1 can determine cardiac xenograft survival. Nature Medicine 4: 1073–1077; 1998.
Motterlini, R., Foresti, R., Bassi, R. and Green, C. J. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radical Biology and Medicine 28: 1303–1312; 2000.
Hygiene hypothesis
Rook, G. A. and Stanford, J. L. Give us this day our daily germs. Immunology Today 19: 113–116; 1998.
Frailty genes in centenarians
Yashin, A. I., De Benedictis, G., Vaupel, J. W., et al. Genes and longevity: lessons from studies of centenarians. Journal of Gerontology 55A: B319–B328; 2000.
Mitochondrial variants and ageing
Tanaka, M., Gong, J. S., Zhang, J., Yoneda, M. and Yagi, K. Mitochondrial genotype associated with longevity. Lancet 351: 185–186; 1998.
Vandenbroucke, J. P. Maternal inheritance of longevity. Lancet 351: 1064; 1999.
FURTHER READING • 359
Ooplasmic transfer and cloning
Barritt, J. A., Brenner, C. A., Malter, H. E. and Cohen, J. Mitochondria in human offspring derived from ooplasmic transplantation. Human Reproduction 16: 513–516; 2001.
Allen J. F. and Allen C. A. A mitochondrial model for premature ageing of somati-cally cloned mammals. Hypothesis paper. IUBMB Life 48: 369–372; 1999.
Lipid composition of mitochondria
Pamplona, R., Portero-Otín, M., Riba, D., Ruiz, C., Prat, J., Bellmunt, M. J. and Barja, G. Mitochondrial membrane peroxidizability index is inversely related to maximum life span in mammals. Journal of Lipid Research 39: 1989–1994; 1998.
Laganiere, S. and Yu, B. P. Modulation of membrane phospholipid fatty acid composition by age and food restriction. Gerontology 39: 7–18; 1993.
Mitochondrial medicine
Hagen, T., Ingersoll, R. T., Wehr, C. M., Lykkesfeldt, J., Vinarsky, V., Bartholomew, J. C., Song M. H. and Ames B. N. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proceedings of the National Academy of Sciences USA 95: 9562–9566; 1998.
Hagen, T. M., Liv, J., Lykkesfeldt, J., Wehr, C. M., Ingersoll, R. T., Vinarsky, V., Bartholomew, J. C. and Ames, B. N. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proceedings of the National Academy of Sciences USA 99: 1870–1875; 2002.
Brierley, E. J., Johnson, M. A., James, O. F. and Turnbull, D. M. Effects of physical activity and age on mitochondrial function. Quarterly Journal of Medicine 89: 251–258; 1996.
Fosslien, E. Mitochondrial medicine — molecular pathology of defective oxidative phosphorylation. Annals of Clinical Laboratory Science 31: 25–67; 2001.
Glossary
AGE (advanced glycation end-product) caramel-like
bacteriochlorophyll form of chlorophyll found in
material formed by the reaction of a protein
the most ancient photosynthetic bacteria,
with glucose and oxygen.
which do not generate oxygen.
age-1 gene that when mutated extends the life-
banded-iron formation rock formation comprising
span of nematode worms.
bands of ironstone (such as magnetite or
allele one of (usually) several variants of the
haematite) alternating with quartz or flint.
same gene.
binary fission bacterial method of cell division by
alpha tocopherol chemical name for the most
doubling cellular material, then splitting in
common form of vitamin E.
two.
amino acids the building blocks that are linked in
biomarker biochemical ‘fingerprint’ that could
chains to form proteins in all living things.
only have been produced by a particular form
Twenty different types are found in proteins;
of life.
the order in which they are linked together is
calorie restriction balanced diet with beneficial
specified by the DNA code.
effects on health and longevity in animals, in
amyloid protein fragment found in senile plaques
which free (unrestricted) calorie intake is
in Alzheimer’s disease.
restricted by 30 to 40 per cent.
anaerobic pertaining to organisms that do not
Cambrian geological period from about 543 to
use oxygen for respiration.
500 million years ago.
anoxygenic photosynthesis ancient form of photo-
Cambrian explosion sudden proliferation of many
synthesis, which uses sunlight to split hydro-
different types of complex animals around the
gen sulphide or iron salts (instead of water)
beginning of the Cambrian period (543
without generating oxygen.
million years ago).
antagonistic pleiotropy trade-off between oppos-
cap carbonates thick belts of limestone capping
ing (antagonistic) effects of a gene that has
glacial deposits laid down in the immediate
more than one effect (pleiotropy).
aftermath of global glaciations.
antigen bacterial protein or other ‘foreign’ par-
carbon burial burial of organic matter as coal, oil
ticle recognized by antibodies or cells of the
or natural gas, as well as barely noticeable
immune system.
carbon deposits in rocks such as sandstone.
antioxidant chemical that hinders the oxidation
carbon signature imbalance in carbon-isotope
of other molecules, such as fats or proteins.
ratios in rocks, betraying the activity of life.
ApoE4 a gene variant associated with a greater
carbonate rocks limestone rocks composed mostly
risk of Alzheimer’s disease.
of calcium and magnesium carbonates.
apoptosis programmed cell death, as opposed to
Carboniferous geological period from about 360
necrosis (unplanned or ‘violent’ cell death).
to 286 million years ago.
Archaea one of the three great domains of life.
cardiolipin lubricating lipid found at high levels
In many respects, archaea are intermediary
in mitochondrial membranes, especially in
between eukaryotes (cells with nuclei) and
physiologically active tissues such as heart
bacteria.
muscle.
ascorbate chemical name for vitamin C.
carnitine a molecular ‘shuttle’ responsible for
ascorbyl radical poorly reactive free radical,
transferring fatty acids into mitochondria for
formed when vitamin C is partially oxidized.
respiration, and left-over organic acids out
ATP (adenosine triphosphate) energy ‘currency’ of
again for disposal.
cells, generated by all forms of aerobic and
catalase enzyme responsible for breaking down
anaerobic respiration, as well as photo-
hydrogen peroxide to oxygen and water.
synthesis.
catalyst molecule that speeds up a chemical
autoimmune disease disease in which the immune
reaction without being altered permanently
system mistakenly attacks components of the
itself.
body rather than bacteria or other ‘foreign’
chain-breaking antioxidant chemical that blocks
particles.
free-radical chain reactions.
GLOSSARY • 361
chloro
phyll plant pigment that captures the
oxygen free radicals elicit the inflammatory
energy of the Sun in photosynthesis, con-
response to infection, so resolving the infec-
verting it into chemical energy.
tion; in ageing, free radical leakage from mito-
chloroplast specialized subcellular ‘organelle’
chondria activates the same inflammatory
containing chlorophyll, which is the site of
response, but because mitochondrial leakage
photosynthesis in algae and plants. Chloro-
is irresolvable, inflammation persists, leading
plasts originally derived from cyanobacteria.
to chronic diseases of old age.
chromosome strand of DNA encoding a number
Ediacaran fauna ancient fossils of primitive
of genes and wrapped in proteins.
animals from the Vendian period (about 570
chronic inflammation continuous, unresolved
million years ago), first discovered in the
inflammation.
Ediacara Hills in Australia.
cofactor molecule required for the proper func-
electromagnetic radiation spectrum of wave-par-
tion of an enzyme.
ticles of defined energy (depending on the
conjugation bacterial equivalent of sex, in which
wavelength), including visible light, infrared
spare genes (usually on small circular chromo-
rays, and ultraviolet rays.
somes called plasmids) are passed from one
electron subatomic wave-particle with negative
bacterium to another.
charge.
cyanobacteria blue-green photosynthetic bacteria
electron donor molecule with chemical tendency
(once called blue-green algae). They have been
to give up one or more electrons to other mol-
the most important producers of oxygen in
ecules (also called a reductant).
the air over evolutionary time.
epithelial cell cell from layer covering internal or
cytochrome oxidase critical enzyme in oxygen-
external surfaces in the body.
requiring respiration, which receives electrons
eukaryote organism with cells having a ‘true
and protons (hydrogen atoms) derived from
nucleus’. Eukaryotes comprise one of the
sugars or fats, and combines them with
three domains of life. Animals, plants, fungi,
oxygen to form water.
algae and protozoa are eukaryotes.
cytoplasm part of the cell outside the nucleus,
euxinic stagnant water saturated with hydrogen
encompassing both the watery cytosol and
sulphide, as in the deep waters of the Black Sea
the membrane-enclosed structures such as
(ancient name, the Euxine).
mitochondria.
fatty acid molecule with a hydrophilic head and
cytosol watery base solution of the cytoplasm.
a long hydrophobic hydrocarbon tail. Fatty
cytosolic SOD iron-zinc superoxide dismutase,
acids are components of fats, oils and mem-
found in the cytosol of eukaryotic cells.
brane lipids.
daf-16 gene that when mutated prolongs the
Fenton reaction reaction of iron with hydrogen
lifespan of nematode worms.
peroxide to form hydroxyl radicals.
daf-2 gene that when mutated prolongs the
fermentation form of anaerobic (oxygen-free)
lifespan of nematode worms.
respiration used by yeasts, which produces
dehydroascorbate oxidized form of vitamin C.
ethanol as an end-product.
differentiation specialization of a cell for a
ferritin cage-like protein that locks away iron
particular task, such as contraction in muscle
within cells.
cells or electrical transmission in neurons.
fibroblast connective-tissue cell, found in skin
diploid containing two equivalent sets of
and bodily organs, and important in healing
chromosomes.
wounds.
disposable soma theory literally the ‘throwaway
free radical atom or molecule with an unpaired
body’ theory. It argues that ageing is the out-
electron. In this book, the term mostly refers
come of a trade-off between resources com-
to reactive forms of oxygen, such as super-
mitted to sex and those committed to bodily
oxide radicals and hydroxyl radicals.
maintenance.
free-radical scavenger molecule that ‘scavenges’
DNA (deoxyribonucleic acid) genetic material of all
(reacts with) free radicals to neutralize them.
cells, twisted into the famous double helix.
free-radical theory of ageing theory arguing that
The sequence of four ‘letters’, A (adenine), T
continuous production of oxygen free radicals
(thymine), C (cytosine), and G (guanine)
during oxygen respiration is the root cause of
encodes the order of amino-acid building
ageing.
blocks in proteins.
gamete sex cell, with half the number of chromo-
dominance power of one gene in a pair of
somes of a somatic (body) cell.
equivalent genes (one inherited from each
gene unit of DNA comprising the coding
parent) to make its own effects felt at the
sequence for a single protein (or RNA mol-
expense of the ‘weaker’ (recessive) gene.
ecule).
double-agent theory theory arguing that oxygen
gene expression active production of the protein
plays a duplicitous role in health. In youth,
or RNA encoded by a gene.
362 • GLOSSARY
genome the complete set of genes of an organ-
inflammation general defensive reaction to infec-
ism.
tion or injury, characterized by heat, redness,
genotype the particular variant of a gene or genes
swelling, and pain. Low-grade, chronic
carried by an individual, which can be used to
inflammation is almost universal in diseases
distinguish one individual from another at
of old age.
the genetic level.
inflammatory cell a cell involved in propagating
germ line the cells responsible for passing genes
inflammation, such as a macrophage or
on to the next generation.
neutrophil.
glutathione small sulphur-containing antioxidant
inflammatory messenger chemical signal produced
that ‘polices’ the oxidation state of cells.
by inflammatory cells to recruit and activate
glycolysis form of anaerobic (oxygen-free) respir-
other inflammatory cells from elsewhere in
ation in which glucose is converted to pyru-
the body.
vate with the generation of a small amount of
infrared radiation electromagnetic rays with wave-
energy. In aerobic cells it is coupled to oxygen
length longer than about 800 nanometres.
respiration to produce more energy.
insulin hormone that promotes uptake of
group selection evolutionary selection of traits
glucose from blood, stimulating protein syn-
that benefi
t populations rather than indi-
thesis, fat deposition, weight gain and sexual
viduals. It is a weak selective force in most
maturation.
circumstances.
insulin-resistance genetic or acquired resistance to
haem pigment molecule containing iron embed-
the effects of insulin.
ded in a porphyrin ring. It is incorporated into
ionizing radiation radiation that dislodges elec-
many proteins, including haemoglobin, cyto-
trons from compounds to produce an electric
chrome oxidase and catalase.
charge.
haem oxygenase important stress protein that
iron pyrites (FeS2), or fool’s gold, formed by the
breaks down haem to release biologically
reaction of hydrogen sulphide (from bacteria
active products: iron, carbon monoxide (an
or volcanoes) with dissolved iron.
signalling molecule at low concentrations)
isotopes different atomic forms of the same
and bilirubin (an antioxidant).
element, with equal numbers of protons
haemoglobin haem-containing oxygen-transport
(making them chemically equivalent) but
molecule packed tightly in red blood cells.
different numbers of neutrons (giving them
haploid containing half the normal two sets of
different molecular weights).
chromosomes, that is, containing a single set.
junk DNA non-coding DNA which apparently
Hayflick limit maximum number of divisions that
serves no purpose; thought to comprise
any given type of somatic (body) cell will
‘selfish’ genes hitching a ride, inserted viral
undergo.
DNA sequences, and defunct genes.
Hox genes ‘master-switch’ genes that regulate
knock-out mice genetically manipulated mice, in
embryonic development in animals as diverse
which specific genes are mutated so that their
as nematode worms, flies, mice and men.
protein products are not expressed.
hydrogen peroxide (H O
lateral gene transfer
2
2) unstable chemical
‘horizontal’ movement of
intermediate between oxygen and water. It is
genes between individuals in a population, as
especially reactive with iron in the Fenton
opposed to ‘vertical’ inheritance from parents