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Bigger animals live longerR.C.DohareBE(Mech.),ME(ESE),MBADr. A. BenjaminJLN hospital Bhilai
All animals eventually grow old and die. It's an inevitable fact of life - except when it isn't. Some animals, like tortoises and lobsters, never grow old, and learning their secrets could let humans live as long as they want.For most animals, there are three basic ways they can die: disease, injury, or old age, which is also called senescence. But a select few species are seemingly immune from aging itself, a phenomenon known as negligible senescence. The gradual accumulation of cellular damage and degradation that will eventually kill other animals (including us) slows to a virtual standstill, prolonging the life - and, in fact, the youth - of any animal lucky enough to be negligibly senescent.
The sizes of organisms range over many orders of magnitude. The largest animals and plants weigh about 21 orders of magnitude (1021 times) more than the smallest microbes (Figure 2). The smallest known organism is the tiny microbe Nanoarchaeum equittans, which lives in hydrothermal vents off the coast of Iceland and measures only 400 nm (≈0.00002 inches). The largest organism is the giant sequoia, Sequaiodendron sempervirens, which can be 100 m tall and 17 m in diameter at its base. To a large extent the diversity of function in life is the result of diversity in size. George Bartholomew (1981) observed that "the most important attribute of an animal, both physiologically and ecologically is its size." Indeed, if we know an animal's mass, we can make accurate educated guesses about many of its characteristics. To see why this is so, we can go back to the ancient Greeks who discovered and applied the principle of geometric similarity: If a collection of objects has the same form, we call them geometrically similar, and surface area (S) increases as the square, and volume (V) as the cube, of linear dimensions. Here it is represented in formulae, taking L to represent any linear dimension (e.g., the total animal's length or the length of one of its legs):
Across all species a gram of tissue on average expends about the same amount of energy before it dies.
Tissues in smaller animals expends more energy before expiring than tissues in large animals. I.e. rate of energy consumption or expenditure more in smaller animal less in bigger animals per unit time.
However smaller individuals with higher rate of metabolism lives longer then their slower.
Mitochondria generate free radicals as a function of metabolism.
RMR/BMR = 0.66 to 0.8 where RMR is resting metabolic rate, BMR= basal metabolic rate.
T= 7.545 M0.2689 A.T.Atansov formula Where T is pregnancy length in days (gestation period), M is body weight in gram, 7.545 allometric constant, 0.2689 power allometric constant
The Atansove develop formula from
Log T = a+b log M T length of pregnancy, M body weight in gram, a= 0.878± 0.060, b=0.2689 ±0.013
Kleiber’s Law,
BMR = 0.442M 0.266
Lpred =21.5 E 0.65 M -0.28 Lpred Expected life predicted of mammals. M is body
Weight in gram, E is brain weight in gram.
T heart ∞ M 1/4 T heart heart beat time of animal, M is body weight in grams
A∞M 1/8 A is Surface area of the animal,
VOptimum ∞ 30 M 1/6 m/sec where VOptimum velocity of bird or animal,
A more straightforward way to the limits of animal locomotion is to look for mass dependence in their maximum velocities. Although the data available is not very accurate, Garland (1983) has plotted the velocity-mass graph, finding
log Vmax= 1.478 + 0.259 log M - 0.062 (log M)2
where Vmax is the maximal velocity (in km/h) of an animal weighing M (in kg). The logarithms are of
base 10. A mass 106 kg allows a running speed of 6 km/h – a man could walk and overtake!
Voxy = 0.2 M 0.76 Voxy volume of oxygen consumption/min, M body weight in kg. For human 0.217 lO2/gram hour
L span = 4×10 8 M 0.2 L span expected life span of an animal. M in kg
Wh= 4M-0.25 Wh heat generation rate of animal of body weight M in kg.
With a 0.5-0.6 0C reduction of CBT( core body temperature) Hcrt UCP2 mice showed up to a 20% increase in the median life expectancy in the absence of CR( calorie Restriction)
F= 0.84 M -0.26 breath/sec F is breathing rate of animal M is weight in gram.
Ke = E/M 0.172 Ke Encephilization Index, E is brain weight, M body weight
in gramLungs capacity of mammals = 56.7M milliliter M in kg, human 7% body weight, hump whale 1-3%
(TLC)= 0.135×M 0.92 for marine animals
0.225×M 0.81 for others
Cuvier’s fraction E/M
Species E/MSmall Birds 1/12Human 1/40Mouse 1/40Cat 1/100Dog 1/125Frog 1/172Lion 1/530Elephant 1/560Horse 1/600 Shark 1/2496Hippopotamus 1/2789
LogL = 0.334+0.252log M
logL = 0.776+0.327log E
log L = 1.33+0.65logE-0.28logM
logMb =0.549+0.723logM , Mb= mass specific metabolic
logL = 0.44+0.68logE0.34logM-0.16log Mb +0.026 T b
log Ks = log Mb - 0.05 T b
Ks= Mb 10 0.5 T b where Mb mass specific metabolic rate, T b
Body temperature
Blue WhaleLungs capacity 5000 literLength 55-65 feet, weight 50 tonsBrain weight 20 pound, largest of all animalsEat 3% of body weight 1 ton/dayIt can reach to the depth of 3KM It can stay there for 30 Min.Life span 70 years+Gestation Period(GP) 14-16 month.Max speed 20 miles/hr.Baby whale weight 1ton average, length 13 feet.Female maturity comes at 7-13 years.A lactation period is 19-42 months.Male reach it full size at the age of 50 years.Breathing rate 3-5 /min during rest, 6-7 after dive.Hummingbirds eat about every ten minutes, slurping down twice their body weight in nectar every dayThe American turkey vulture helps human engineers detect cracked or broken underground fuel pipes. The leaking fuel smells like vulture food (they eat carrion), and the clustered birds show repair people where the lines need fixing.
A bird's heart beats 400 times per minute while resting and up to 1000 beats per minute while flying
Falcons can swoop at over 200 mph
following table gives the average heart rates of some common mammals.
Heart Rates Comparison (beats/minute)
Organism Average Rate Normal Range
Human 70 58 - 104
Cat 120 110 - 140
Cow 65 60 - 70
Dog 115 100 - 130
Guinea Pig 280 260 - 400
Hamster 450 300 - 600
Horse 44 23 - 70
Rabbit 205 123 - 304
Rat 328 261 - 600
The heart rate of amphibians and reptiles is very dependent upon temperature. For example, the following table gives the approximate heart rate of a crocodile at the indicated temperatures. Notice that the higher the temperature, the faster the heart beat.
Temperature (Celsius)
Average Rate (beats/minute)
10 C 1 - 8
18 C 15 - 20
28 C 24 - 40
>40 C Irreversible cardiac damage
Typical values for vertebrates, where MR is in ml O2/hour, W in grams
______________________________________________________________________________
Taxon a b time (h) for a 1 g animal to use 10 ml O2
______________________________________________________________________________
Endotherms
passerine bird (42ºC) 7.5 .72 1.3
placental mammal(37ºC) 3.8 .75 2.6
marsupial (35ºC) 2.3 .75 4.3
average = 4.5 .74 2.2
Ectotherms
lizard (37ºC) .42 .82 23.8
frog (ranid) (25ºC) .29 .75 ? calculate
fish (25ºC) .20 .70 50
beetles (22-25ºC) .23 .86 ? calculate
average = 0.4 .78 43.5
______________________________________________________________________________
African Grey Parrot 73 Amazon Parrot 104
American Alligator 56 American Box Turtle 123
American Newt 3 American Toad 15
Angleworm 15 Anole 3
Ant --Queen 3 Ant -- Worker 1/2
Banksian Cockatoo 29.3 Bat 24
Bear 40 Beaver 20
Bee -- Queen 5 Bee -- Worker 1
Binturong 18 Blackbird(redwinged) 15.8
Boa Constrictor 23 Budgerigar 29
Bull 28 Bull Frog 16
Bull Snake 18 Caiman 28
Camel 50 Canada Goose 24.3
Canary 24 Canvasback duck 22.4
Capybara 12 Carp 100
Cat 25 Chicken 14
Chinchilla 20 Civet 13
Cockatiel 35 Common Goldeneye 14.3
Congo Eel 27 Conure 22.5
Cottonmouth Mocassin 21 Cow 22
Crocodile 45 Deer 26.8
Dog 22 Domestic Pigeon 18
Donkey 45 Eclectus Parrot 30
Egyptian Goose 25.5 Elephant 70
Fence Lizard 4 Ferret 12
Flying Squirrel 14 Fox 14
Galah 27.2 Galapagos Land Tortoise 193
Gerbil 5 Goat 15
Golden Hamster 4 Gouldian finch 14
Grey Cheeked Parrot 15 Grey Squirrel 20
Grouse (blue) 14 Guinea Pig 8
Hare 10 Hellbender 29
Hippopotamus 45 Hog 18
Horse 40 Kangaroo 9
Koala 8 Leopard Frog 6
Lion 35 Macaw 64
Mallard 29 Mongoose 12
Mouse 4 Muscrat 6
Mudpuppy 9 Mynah 25
Norwegian Rat 4 Nutria 15
Opossum 4 Ox 20
Painted Turtle 11 Pea Fowl 23.2
Pheasant 27 Pig -- wild 25
Pionus Parrot 40 Platypus 10
Porcupine 20 Prarie Dog 10
Quail (California) 6.9 Rabbit 9
Rainbow Lorikeet 15 Rat Snake 23
Rattlesnake 22 Red Eared Turtle 30.5
Ring-necked Duck 20.4 Rhinoceros 40
Rosella 15.4 Sheep 15
Snapping Turtle 57 South African Clawed Toad 15
Sulphur Crested Cockatoo 80 Superb Parrot 36
Tapir 30 Tasmanian Tiger 7
Teal 22.3 Tiger 22
Tiger Salamander 11 Toucan 20
Tree Frog 14 Trumpeter Swan 33
Wood Duck 22.5 Wombat 15
Wolf 18 Woodchuck 15
Zebra Finch 12
Max Kleiber, a nutritionist at the University of California published a data set that included mammals of a much wider range of sizes. Like Rubner, Kleiber found that the rate of energy use in mammals increased with mass. But unlike Rubner, he found that the exponent of the relationship was not 2/3 but instead was close to 3/4 (0.75), which Kleiber suggested should be used (Figure 3). Kleiber's suggestion of using an exponent of 0.75 was subsequently adopted, and Kleiber's law supplanted Rubner's rule.
Figure 3: Max Kleiber's (1947) original figure reporting the relationship between the metabolic rate of a collection of mammals and body massNote that the relationship has a gradient that differs from both 1 and 2/3.
Why Temperature Matters
We can say much about an organism if we know how big it is. We can say more if, in addition, we know how hot it is. The relationship between how fast biological processes take place has been known for a long time. Harold Shapley, who is better known as an astronomer than an ant-watcher, found that the speed at which ants ran along the trails of Mount Wilson Observatory increased so regularly with temperature that he could use ant speed as an accurate thermometer. Recognizing that the speed of biological processes increases roughly exponentially with temperature, physiologists devised a thermal sensitivity index called the Q10 factor. Q10 simply tells you the factor by which the reaction increases when you raise temperature by 10 degrees centigrade (or Kelvin). If temperature equals T and rate equals q, then Q10 equals the ratio of the rate of the process at T + 10 [q (T + 10)] divided by that at T[q
(T)]:
A better relationship was derived for chemical reactions by the pioneering physical chemists Jacob Van't Hoff and Svante Arrhenius in the late nineteenth century:
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Ea and kB are the "energy of activation" and Boltzmann constant, respectively. The Arrhenius equation is
particularly convenient in its linearized form
which tells you that if you plot the natural log of the rate (q) in the y axis, and the reciprocal of temperature (T in degrees Kelvin) in the x axis, you get a straight line with gradient equal to -Ea/kB. For organisms, both the Q10 and the Arrhenius equation are only convenient approximations. They work adequately well in a portion of the narrow range of temperatures that are suitable for life (0–40°C), but for most organisms, they do not work outside this range. Enzymes are very susceptible to thermal inactivation at high temperatures, and most metabolic processes cease around 0°C. As usual, microbes are an exception: Archaea from hydrothermal vents can thrive at temperatures higher than 100° C and the bacterium Psychrobacter cryopegella, found in Siberian permafrost, can remain active and grow at temperatures as low as -10°C. Most organisms can only live if their body temperature is within an interval of temperatures that is narrower than the full range of temperature occupied by life. Thus, some Antarctic fishes die if you place them in water that is only 6°C (42.8°F)! The relatively narrow range of temperatures at which the life processes of an organism can take place makes the relationship between biological rates and temperature within a single species humped-shaped and asymmetrical (Figure 4).
The Metabolic Theory: Combining Allometry and Temperature
With remarkable insight, James Gillooly and his collaborators at the University of New Mexico conjectured that we can estimate metabolic rate (B) as the product of an allometric function and the
Arrhenius equation:
This simple equation has enormous descriptive power, and is at the center of what is called the metabolic theory of ecology (MTE). MTE aims to find the relationship between body mass and temperature and a variety of ecological phenomena, and does it successfully. MTE's central equation is very useful for four major reasons:
1. It summarizes a lot of biological information in a very compact form.
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2. We can combine it with other equations to make a variety of inferences about ecological processes that range from the behavior of individuals to the biogeochemical processes in ecosystems.
3. MTE's central equation can be used to make educated guesses ("first order predictions") about features of organisms and magnitudes of ecological processes that have not been studied directly. We use the term educated guesses because, although MTE's predictions can be quite accurate, they are also rather imprecise.
4. MTE's central equation allows us to make comparisons between the traits of different organisms that might differ in body mass and temperature.
MTE's equation allows us to ask if the traits of organisms vary only because of differences in body mass and temperature or because other factors are at play. Because body mass and temperature have such pervasive effects on all biological processes, we need to account for their differences in both body mass and temperature when we compare the traits of different species. For example, if we want to know whether animals that live in arid places have larger home ranges than those that live in moister, more productive places, we need to account for the observation that the animals that we want to compare
might differ in both size and body temperature.
Simple scaling laws are not limited to metabolic
rates, (a) A log-lofi plot of heart rate as a function
of body mass for a variety of mammals.
Ceils in living organisms and cells cullured in
vitro have different metabolic rates. The plot shows the
metabolic rates of mammalian cells in vivo (blue) and in
vitro (red) as a function of organism mass M. While slill
in the body and constrained by vascular supply networks,
cellular metabolic rates scale as M '•' (blue line).
Cells removed from the body and cultured in vitro generally
take on a constani metabolic rale (red line) predicted
by theory. Consistent with theory, the in vivo and in vitro
lines meet at the mass M,,^,, of a theoretical smallest
mammal, which is close to that of a shrew.
(Adapted from rel. 6.)
Types and Frequency of DNA Damage
TYPE OF DAMAGEevents/cell/day % of total daily damage
Single-strand break 120,000 50.9
N7-MethylGuanine 84,000 35.6
Depurination 24,000 10.2
O6-MethylGuanine 3,120 1.3
Oxidized DNA 2,880 1.2
Depyrimidation 1,320 0.5
Cytosine deamination 360 0.2
Double-strand breaks 9 0.01
Interstrand cross-links 8 0.0
rrr correlated with Maximum Life Span (MLS)
rrr = rat-relative repair (rat DNA−repair = = 1.0)
Organism Scientific nameDiploid number of chromosomes
Notes
Adders-tongue Ophioglossum reticulatum 1440 This fern has the highest known
chromosome number.Field Horsetail Equisetum arvense 216Rattlesnake fern Botrypus virginianus 184[1]
Carp 104
Kamraj (fern) Helminthostachys zeylanica 94
Aquatic Rat Anotomys leander 92[2] Tied for highest number in mammals with Ichthyomys pittieri.
Shrimp Penaeus semisulcatus 86-92 [3]
Crab-eating rat (semiaquatic rodent) Ichthyomys pittieri 92[2] Tied for highest number in mammals with
Anotomys leander.Grape ferns Sceptridum 90Hedgehog Genus Atelerix (African hedgehogs)
90
Moonworts Botrychium 90Hedgehog Genus Erinaceus (Woodland hedgehogs)
88
Nagaho-no-natsu-no-hana-warabi Botrypus strictus 88
B. strictus and B. virginianus have been shown to be paraphyletic in the genus Botrypus
Organism Scientific nameDiploid number of chromosomes
Notes
Pigeon 80Turkey 80[4]
African Wild Dog Lycaon pictus 78[5]
Chicken Gallus gallus domesticus 78Coyote Canis latrans 78[5]
Dhole Cuon alpinus 78Dingo Canis lupus dingo 78[5]
Dog Canis lupus familiaris 78[6] 76 autosomal and 2 sexual.[7]
Dove 78[8] Based on African collared doveGolden Jackal Canis aureus 78[5]
Wolf Canis lupus 78Maned Wolf Chrysocyon brachyurus 76Bat-eared Fox Otocyon megalotis 72[5]
Black nightshade Solanum nigrum 72[9]
White-tailed deer Odocoileus virginianus 70Elk (Wapiti) Cervus canadensis 68Red Deer Cervus elaphus 68
Gray Fox Urocyon cinereoargenteus 66[5]
Raccoon Dog Nyctereutes procyonoides 66 Some variation in the number of
chromosomes between individuals [10]
Chinchilla Chinchilla lanigera 64 [11]
Echidna 63/64 63 (XXY, male) and 64 (XXXX, female)Fennec Fox Vulpes zerda 64[5]
Horse Equus ferus caballus 64Spotted Skunk Spilogale x 64Mule 63 semi-infertileDonkey Equus africanus asinus 62Giraffe Giraffa camelopardalis 62Gypsy moth 62Bengal Fox Vulpes bengalensis 60Cow Bos primigenius 60Goat 60
Woolly Mammoth Mammuthus primigenius 58 extinct; tissue from a frozen carcass
Elephant 56Capuchin Monkey Cebus x 54[12]
Sheep 54
Hyrax Hyracoidea 54[13] Hyraxes are considered to be the closest living relative to the Elephant.[14]
Cotton Gossypium hirsutum 52[15] 2n=4x; Cultivated upland cotton is derived from an allotetraploid
Duck-billed Platypus 52
Platypus Ornithorhynchus anatinus 52 [16] Ten sex chromosomes.
Organism Scientific nameDiploid number of chromosomes
Notes
Kit Fox 50Pineapple Ananas comosus 50[15]
Striped skunk Mephitis mephitis 50Beaver (Eurasian) Castor fiber 48Chimpanzee Pan troglodytes 48[17]
Deer Mouse Peromyscus maniculatus 48Gorilla 48Hare [18] [19] 48Orangutan Pongo x 48
Potato Solanum tuberosum 48 This is a tetraploid; wild relatives mostly have 2n=24.[15]
Tobacco Nicotiana tabacum 48 Cultivated species is a tetraploid.[15]
Human Homo sapiens 46 44 autosomal and 2 sexReeves's Muntjac Muntiacus reevesi 46Sable Antelope Hippotragus niger 46Dolphin Delphinidae Delphis 44Eurasian Badger Meles meles 44Rabbit 44Fossa Cryptoprocta ferox 42
Oats Avena sativa 42This is a hexaploid with 2n=6x=42. Diploid and tetraploid cultivated species also exist.[15]
Raccoon Dog Nyctereutes viverrinus 42 some sources say sub-species differ with 38, 54, and even 56 chromosomes
Rat 42Rhesus Monkey 42[
Wheat Triticum aestivum 42This is a hexaploid with 2n=6x=42. Durum wheat is Triticum turgidum var. durum, and is a tetraploid with 2n=4x=28.[15]
Wolverine Gulo gulo 42Beaver (American) Castor canadensis 40European Polecat Mustela putorius 40Ferret Mustela putorius furo 40Hyena 40Mango Mangifera indica 40Mouse Mus musculus 40American Marten Martes americana 38Beech Marten Martes foina 38Cat Felis catus 38Coatimundi 38European Mink Mustela lutreola 38Fisher (animal) 38 a type of martenLion Panthera leo 38Oriental Small-clawed Otter Aonyx cinerea 38
Organism Scientific nameDiploid number of chromosomes
Notes
Pig 38Pine Marten Martes martes 38Raccoon Procyon lotor 38Sable Martes zibellina 38Sea Otter 38
Tanuki/Raccoon Dog Nyctereutes procyonoides albus 38
Tiger Panthera tigris 38Earthworm Lumbricus terrestris 36Long-nosed Cusimanse (a type of mongoose) 36
Meerkat Suricata suricatta 36Red Panda 36Starfish 36Tibetan sand fox Vulpes ferrilata 36Yellow Mongoose Cynictis penicillata 36Porcupine Erethizon dorsatum 34 Red Fox Vulpes vulpes 34 Plus 3-5 microsomes.
Alfalfa Medicago sativa 32 Cultivated alfalfa is tetraploid, with 2n=4x=32. Wild relatives have 2n=16.[15]
American Badger Taxidea taxus 32
European honey bee Apis mellifera 32 32 for females, males are haploid and thus have 16.
Yeast Saccharomyces cerivisiae 32
American Mink Neovison vison 30
Pill millipede Arthrosphaera magna attems 30 [23]
Zebrafish Danio rerio 26Bittersweet nightshade Solanum dulcamara 24Husk Tomato Physalis pubescens 24Silverleaf nightshade Solanum elaeagnifolium 24Rice Oryza sativa 24Snail 24
Bean Phaseolus sp. 22
All species in the genus have the same chromosome number, including P. vulgaris, P. coccineus, P. acutifolis,and P. lunatus.[15]
Virginia Opossum Didelphis virginiana 22Cannabis Cannabis sativa 20Maize Zea mays 20
Cabbage Brassica oleracea 18
Broccoli, cabbage, kale, kohlrabi, brussels sprouts, and cauliflower are all the same species and have the same chromosome number.[15]
Organism Scientific nameDiploid number of chromosomes
Notes
Radish Raphanus sativus 18
Kangaroo 16This includes several members genus Macropus, but not the red kangaroo (M. rufus, 40)[29]
Barley Hordeum vulgare 14Pea Pisum sativum 14Rye Secale cereale 14
Slime Mold Dictyostelium discoideum 12
Swamp Wallaby Wallabia bicolor 10/11 11 for male, 10 for female[31]
Nematode Caenorhabditis elegans 12/11 12 for hermaphrodites, 11 for malesThale Cress Arabidopsis thaliana 10
Fruit fly Drosophila melanogaster 8 6 autosomal, and 2 sexual
Hawkweed 8
Mosquito Aedes aegypti 6
The 2n=6 chromosome number is conserved in the entire family Culicidae, except in Chagasia bathana which has 2n=8.[33]
Spider mite 4–14Spider mites (family Tetranychidae) are typically haplodiploidy (males are haploid, while females are diploid)[34]
Jack jumper ant Myrmecia pilosula
22 for females, males are haploid and thus have 1; smallest number possible. Other ant species have more chromosomes.[35]
DNA Repair and Ageing
Life-span, diet and DNA
Why do tortoises live so long? It is not uncommon for a giant tortoise to reach 150 years in age. Some have even suggested there is a Galapagos tortoise old
Organism Scientific nameDiploid number of chromosomes
Notes
enough to have met Charles Darwin. Darwin himself only lived for half as long - still rather longer than the average human of his day. Since the 1800s, improvements in lifestyle and medicine now mean that humans in developed nations live on average 20 years longer. Not quite tortoise potential.
Scientists have come up with some interesting ideas, which might cast light on why different species have different life-spans. One such theory relates to metabolism. Humans and other mammals have higher metabolic rates than their reptilian counterparts. We make all our own heat rather than absorbing it from the sun. As we breathe in the air around us, oxygen diffuses into our cells, fuelling the combustive process of respiration, the driving force behind our metabolism, growth and development.
While we make energy from food in this way, hazardous by-products are created that can damage our DNA, so-called reactive-oxygen species (ROS). The higher the metabolic rate, the greater the damage potential and the more likely our cells are to mutate and malfunction. Reptiles, like tortoises might be less susceptible to DNA damage caused by ROS, because they produce lower levels of these reactive chemicals.
We don't know how much DNA damage speeds up ageing or indeed how much it is relevant to the natural ageing process, but recent research suggests that knowing more about our genetic maintenance might improve our quality of life. There's no point in living as long as a tortoise if you're not fit enough to enjoy it.
Life-span, diet and DNA
Dietary research on mice, monkeys, rats, spiders, fruit-flies and worms further emphasizes the link between metabolism and life-span. Severely restricting calorie intake (60-70% of our daily intake) can prolong life-span, given sufficient vitamins, minerals and other nutrients. The thinking is that fewer calories will result in a lower metabolic rate, less ROS and therefore less damage to DNA.
"That is the secret behind calorie restriction prolonging life-span in a natural manner," saysJan Hoeijmakers (Department of Cell Biology and Genetics, Erasmus, Rotterdam), whose team is researching the role of DNA damage in ageing. He and others support the view that calorie restriction reduces metabolism, lowering ROS and the resultant stress on the DNA repair system thereby keeping cells healthier for longer.
Organism Scientific nameDiploid number of chromosomes
Notes
Reactive oxygen species are charged molecules that can disrupt or alter energy bonds between other molecules. Chemicals like superoxide and hydrogen peroxide result from respiration in the powerhouses (mitochondria) of our cells. Neither chemical alone can harm DNA, but in the presence of iron or copper ions they form hydroxyl radicals that can damage organic bases (A, T, C or G) in DNA, which can translate through to protein function. Removal of damaged bases is estimated to occur 20 000 times a day in each body cell. Needless to say adequate measures must be taken to prevent chaos in the cell. Luckily we have a network of sophisticated DNA repair systems policing our genes and keeping genetic order. Scientists have identified well over a hundred genes involved in the various DNA repair pathways that both signal damage and effect a repair response. Ongoing research efforts continue daily to find pieces of this complex molecular jigsaw puzzle.
While DNA damage hasn't been shown to cause ageing directly, a number of rare human disorders, caused by mutations in DNA repair genes, include symptoms of premature ageing. Jan Hoeijmaker's team at Erasmus, in a recent Nature publication (Niedernhofer et al 2006), describe a new ageing syndrome in a teenage boy who encountered the fate of an old man before he even reached puberty.
The patient had mutation in a gene (called XPF) involved together with its partner ERCC1 in DNA repair. The two-protein complex (called XPF/ERCC1) protects against the kind of DNA damage caused by UV sunlight, which can mess up the DNA sequence (see DNA in human disorders). Mutations in the XPF gene are known to cause a rare condition known as Xeroderma pigmentosum (XP). Patients with XP are so sensitive to sunlight, they must completely cover themselves when they go outside and when indoors, live with curtains and shutters drawn. Failure to do so results in skin-cancer.
Patient 'XFE' was sensitive to sunlight, but more dramatic in his case, was the wizened, wasted appearance he developed by the age of 15, not characteristic of XP patients, who usually die from cancer later in life. He was blind and deaf and many of his body organs had wasted away. Jan explains that mutations in the XPF gene can be mild to extreme, mild mutations associating with cancers, in particular skin cancer, and severe mutations with premature ageing, as in the case of patient 'XFE'.
The Dutch team has created mouse models defective in the XPF/ERCC1 protein
Organism Scientific nameDiploid number of chromosomes
Notes
complex that map closely to the clinical conditions of patient 'XFE'. Mice with a defect in the ERCC1 protein also age prematurely and die after a few weeks. When Jan's group analysed genes in the liver of defective mice, well-over 1500 genes showed altered activity when compared to age-matched normal mice. The team confirmed that the same alterations to liver, a key player in metabolism, occur in naturally aged mice.
Among such changes is a low level of insulin-like growth factor-1(IGF-1). This protein-hormone, made and released into the bloodstream by the liver, normally boosts growth. Jan argues that the low levels of IGF-1 in aged and DNA-repair defective mice embody a stress-response that shifts priority from growth and development to maintenance and repair in the face of increasing DNA damage.
"Using the rapidly aging mouse mutants, our intention is to efficiently identify compounds in food or drugs that improve the heath status and life span of the mice. So I started up a company called DNage (recently acquired by Pharming ), whose mission is to provide solutions for medical/health care problems associated with ageing."
The links between the growth hormone axis, the DNA repair system and the 'ageing process' warrant further research, of which the above mentioned studies are an important step in the right direction. Jan is hopeful that with a better understanding of DNA damage, diet and ageing, we can significantly improve the quality of life for those living longer.
Texts by Brona McVittie, Science Writer, London, UK.
Changes in metabolic rate with changes in temperature: The hypothetical organism has a Q10 of 2, that is, its metabolic rate doubles with every 10oC rise in temperature. This rise is the result of the greater thermal energy of the reactants in the cell and the increasing effectiveness of the cellular enzymes. The abrupt decline above 40o represents the point at which the weak bonds that hold enzymes in their specific active conformations begin to break. As a result the enzymes become denatured and metabolic activity is severely disrupted.
Ref:-1. List of organisms by chromosome count Wikipedia, the free encyclopedia 2. Mechanisms of Aging by Ben Best 3. BRAllometric scaling of biological rhythms in mammals BRUNO GÜNTHER1 and ENRIQUE MORGADO2, 3 Biol Res 38: 207-212, 2005 4. Life's Universal Scaling Laws Geoffrey B. West and James H. Brown September 2004 Physics Today 5. Review,Body size, energy metabolism and lifespan- John R. SpeakmanAberdeen Centre for Energy regulation and Obesity (ACERO), School of Biological Sciences, University of Aberdeen,Aberdeen AB24 2TZ, Scotland, UK -mail: [email protected] Accepted 23 February 2005
