Bigger animals live longer

R.C.Dohare BE(Mech.),ME(ESE),MBA Dr. A. Benjamin JLN 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. 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

T= 7.545 M0.2689

The Atansove develop formula from

Log T = a+b log M

Kleibers Law,

T length of pregnancy, M body weight in gram, a= 0.878 0.060, b=0.2689 0.013

BMR = 0.442M
Lpred =21.5 E
0.65

0.266

-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 AM 1/8

T heart heart beat time of animal, M is body weight in grams

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 L span = 410 8 M 0.2 Wh= 4M-0.25 F= 0.84 M -0.26

Voxy volume of oxygen consumption/min, M body weight in kg. For human 0.217 lO2/gram hour L span expected life span of an animal. M in kg 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)

breath/sec

F is breathing rate of animal M is weight in gram.

Ke = E/M 0.172
(TLC)= 0.135M 0.92 0.225M 0.81

Ke Encephilization Index, E is brain weight, M body weight

in gram Lungs capacity of mammals = 56.7M milliliter M in kg, human 7% body weight, hump whale 1-3% for marine animals

for others

Cuviers fraction E/M

Species Small Birds Human Mouse Cat Dog Frog Lion Elephant Horse Shark Hippopotamus E/M 1/12 1/40 1/40 1/100 1/125 1/172 1/530 1/560 1/600 1/2496 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

where Mb mass specific metabolic rate, T b

Ks= Mb 10 0.5 T b
Body temperature

Blue Whale Lungs capacity 5000 liter Length 55-65 feet, weight 50 tons Brain weight 20 pound, largest of all animals Eat 3% of body weight 1 ton/day It 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 day The 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 Human Cat Cow Dog Guinea Pig Hamster Horse Rabbit Rat Average Rate 70 120 65 115 280 450 44 205 328 Normal Range 58 - 104 110 - 140 60 - 70 100 - 130 260 - 400 300 - 600 23 - 70 123 - 304 261 - 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) 10 C 18 C 28 C >40 C Average Rate (beats/minute) 1-8 15 - 20 24 - 40 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 (42C) placental mammal(37C) marsupial (35C) average = Ectotherms lizard (37C) frog (ranid) (25C) fish (25C) beetles (22-25C) average = .42 .29 .20 .23 0.4 .82 .75 .70 .86 .78 23.8 ? calculate 50 ? calculate 43.5 7.5 3.8 2.3 4.5 .72 .75 .75 .74 1.3 2.6 4.3 2.2

______________________________________________________________________________

African Grey Parrot American Alligator

73 56

Amazon Parrot American Box Turtle

104 123

American Newt Angleworm Ant --Queen Banksian Cockatoo Bear Bee -- Queen Binturong Boa Constrictor Bull Bull Snake Camel Canary Capybara Cat Chinchilla Cockatiel Congo Eel

3 15 3 29.3 40 5 18 23 28 18 50 24 12 25 20 35 27

American Toad Anole Ant -- Worker Bat Beaver Bee -- Worker Blackbird(redwinged) Budgerigar Bull Frog Caiman Canada Goose Canvasback duck Carp Chicken Civet Common Goldeneye Conure

15 3 1/2 24 20 1 15.8 29 16 28 24.3 22.4 100 14 13 14.3 22.5

Cottonmouth Mocassin

21

Cow

22

Crocodile Dog Donkey Egyptian Goose

45 22 45 25.5

Deer Domestic Pigeon Eclectus Parrot Elephant

26.8 18 30 70

Fence Lizard Flying Squirrel

4 14

Ferret Fox

12 14

Galah

27.2

Galapagos Land Tortoise

193

Gerbil Golden Hamster Grey Cheeked Parrot Grouse (blue) Hare Hippopotamus Horse Koala Lion Mallard Mouse Mudpuppy Norwegian Rat Opossum Painted Turtle Pheasant Pionus Parrot Porcupine Quail (California)

5 4 15 14 10 45 40 8 35 29 4 9 4 4 11 27 40 20 6.9

Goat Gouldian finch Grey Squirrel Guinea Pig Hellbender Hog Kangaroo Leopard Frog Macaw Mongoose Muscrat Mynah Nutria Ox Pea Fowl Pig -- wild Platypus Prarie Dog Rabbit

15 14 20 8 29 18 9 6 64 12 6 25 15 20 23.2 25 10 10 9

Rainbow Lorikeet Rattlesnake Ring-necked Duck Rosella

15 22 20.4 15.4

Rat Snake Red Eared Turtle Rhinoceros Sheep

23 30.5 40 15

Snapping Turtle

57

South African Clawed Toad

15

Sulphur Crested Cockatoo

80

Superb Parrot

36

Tapir Teal Tiger Salamander Tree Frog Wood Duck Wolf Zebra Finch

30 22.3 11 14 22.5 18 12

Tasmanian Tiger Tiger Toucan Trumpeter Swan Wombat Woodchuck

7 22 20 33 15 15

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)]:
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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
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uninitedaudio

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 (040C), 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 0C. 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 -10C. 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 6C (42.8F)! 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:
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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. 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 events/cell/day % of total daily damage TYPE OF DAMAGE Single-strand break N7-MethylGuanine Depurination O6-MethylGuanine Oxidized DNA Depyrimidation Cytosine deamination Double-strand breaks 120,000 84,000 24,000 3,120 2,880 1,320 360 9 50.9 35.6 10.2 1.3 1.2 0.5 0.2 0.01

Interstrand cross-links

0.0

rrr correlated with Maximum Life Span (MLS)

rrr = rat-relative repair (rat DNArepair = = 1.0)

Organism

Scientific name Ophioglossum reticulatum Equisetum arvense Botrypus virginianus Helminthostachys zeylanica Anotomys leander Penaeus semisulcatus Ichthyomys pittieri Sceptridum

Diploid number of chromosomes 1440 216 184 104 94 92

[2] [3] [1]

Notes This fern has the highest known chromosome number.

Adders-tongue Field Horsetail Rattlesnake fern Carp Kamraj (fern) Aquatic Rat Shrimp Crab-eating rat (semiaquatic rodent) Grape ferns Hedgehog Genus Atelerix (African hedgehogs) Moonworts Hedgehog Genus Erinaceus (Woodland hedgehogs) Nagaho-no-natsu-no-

Tied for highest number in mammals with Ichthyomys pittieri. Tied for highest number in mammals with Anotomys leander.

86-92 92 90 90
[2]

Botrychium

90 88

Botrypus strictus

88

B. strictus and B. virginianus have been

hana-warabi Pigeon Turkey African Wild Dog Chicken Coyote Dhole Dingo Dog Dove Golden Jackal Wolf Maned Wolf Bat-eared Fox Black nightshade White-tailed deer Elk (Wapiti) Red Deer Gray Fox Raccoon Dog Chinchilla Echidna Fennec Fox Horse Spotted Skunk Mule Donkey Giraffe Gypsy moth Bengal Fox Cow Goat Woolly Mammoth Elephant Capuchin Monkey Sheep Hyrax Cotton Hyracoidea Gossypium hirsutum Cebus x Mammuthus primigenius Vulpes bengalensis Bos primigenius Equus africanus asinus Giraffa camelopardalis Vulpes zerda Equus ferus caballus Spilogale x Canis aureus Canis lupus Otocyon megalotis Solanum nigrum Odocoileus virginianus Cervus canadensis Cervus elaphus Urocyon cinereoargenteus Nyctereutes procyonoides Chinchilla lanigera Lycaon pictus Canis latrans Cuon alpinus Canis lupus dingo Canis lupus familiaris 80 80 78 78 78 78 78 78 78 78 72 72 70 68 68 66 66 64 64 64 64 63 62 62 62 60 60 60 58 56 54 54 54 52
[13] [15] [12] [11] [5] [5] [9] [5] [6] [8] [5] [4] [5]

shown to be paraphyletic in the genus Botrypus

Gallus gallus domesticus 78

[5]

76 autosomal and 2 sexual.

[7]

Based on African collared dove

Chrysocyon brachyurus 76

Some variation in the number of [10] chromosomes between individuals 63 (XXY, male) and 64 (XXXX, female)

63/64
[5]

semi-infertile

extinct; tissue from a frozen carcass

Hyraxes are considered to be the closest [14] living relative to the Elephant. 2n=4x; Cultivated upland cotton is

derived from an allotetraploid Duck-billed Platypus Platypus Kit Fox Pineapple Striped skunk Beaver (Eurasian) Chimpanzee Deer Mouse Gorilla Hare
[18][19]

52 Ornithorhynchus anatinus Ananas comosus Mephitis mephitis Castor fiber Pan troglodytes 52 50 50 50 48 48 48 48 Pongo x Solanum tuberosum Nicotiana tabacum Homo sapiens Muntiacus reevesi Hippotragus niger Delphinidae Delphis Meles meles Cryptoprocta ferox Avena sativa Nyctereutes viverrinus 48 48 48 46 46 46 44 44 44 42 42 42 42 42 Triticum aestivum Gulo gulo Castor canadensis Mustela putorius Mustela putorius furo Mangifera indica Mus musculus Martes americana Martes foina Felis catus 42 42 40 40 40 40 40 40 38 38 38
[ [17] [15] [16]

Ten sex chromosomes.

Peromyscus maniculatus 48

Orangutan Potato Tobacco Human Reeves's Muntjac Sable Antelope Dolphin Eurasian Badger Rabbit Fossa Oats Raccoon Dog Rat Rhesus Monkey Wheat Wolverine Beaver (American) European Polecat Ferret Hyena Mango Mouse American Marten Beech Marten Cat

This is a tetraploid; wild relatives mostly [15] have 2n=24. Cultivated species is a tetraploid. 44 autosomal and 2 sex
[15]

This is a hexaploid with 2n=6x=42. Diploid and tetraploid cultivated species also [15] exist. some sources say sub-species differ with 38, 54, and even 56 chromosomes

This is a hexaploid with 2n=6x=42. Durum wheat is Triticum turgidum var. durum, [15] and is a tetraploid with 2n=4x=28.

Coatimundi European Mink Fisher (animal) Lion Oriental Small-clawed Otter Pig Pine Marten Raccoon Sable Sea Otter Tanuki/Raccoon Dog Tiger Earthworm Long-nosed Cusimanse (a type of mongoose) Meerkat Red Panda Starfish Tibetan sand fox Yellow Mongoose Porcupine Red Fox Alfalfa American Badger European honey bee Yeast American Mink Pill millipede Zebrafish Husk Tomato Silverleaf nightshade Rice Snail Bean Phaseolus sp. Vulpes ferrilata Cynictis penicillata Erethizon dorsatum Vulpes vulpes Medicago sativa Taxidea taxus Apis mellifera Saccharomyces cerivisiae Neovison vison Arthrosphaera magna attems Danio rerio Physalis pubescens Oryza sativa Suricata suricatta Nyctereutes procyonoides albus Panthera tigris Lumbricus terrestris Martes martes Procyon lotor Martes zibellina Panthera leo Aonyx cinerea Mustela lutreola

38 38 38 38 38 38 38 38 38 38 38 38 36 36 36 36 36 36 36 34 34 32 32 32 32 30 30 26 24 24 24 24 22 All species in the genus have the same chromosome number, including P. vulgaris, P. coccineus, P. acutifolis,and P. [15] lunatus.
[23]

a type of marten

Plus 3-5 microsomes. Cultivated alfalfa is tetraploid, with [15] 2n=4x=32. Wild relatives have 2n=16. 32 for females, males are haploid and thus have 16.

Bittersweet nightshade Solanum dulcamara

Solanum elaeagnifolium 24

Virginia Opossum Cannabis Maize Cabbage Radish Kangaroo Barley Pea Rye Slime Mold Swamp Wallaby Nematode Thale Cress Fruit fly Hawkweed Mosquito

Didelphis virginiana Cannabis sativa Zea mays Brassica oleracea Raphanus sativus

22 20 20 18 18 16 This includes several members genus Macropus, but not the red kangaroo (M. [29] rufus, 40) Broccoli, cabbage, kale, kohlrabi, brussels sprouts, and cauliflower are all the same species and have the same chromosome [15] number.

Hordeum vulgare Pisum sativum Secale cereale Dictyostelium discoideum Wallabia bicolor Arabidopsis thaliana Drosophila melanogaster

14 14 14 12 10/11 10 8 8 6 autosomal, and 2 sexual 11 for male, 10 for female

[31]

Caenorhabditis elegans 12/11

12 for hermaphrodites, 11 for males

Aedes aegypti

The 2n=6 chromosome number is conserved in the entire family Culicidae, except in Chagasia bathana which has [33] 2n=8. Spider mites (family Tetranychidae) are typically haplodiploidy (males are [34] haploid, while females are diploid) 2 for females, males are haploid and thus have 1; smallest number possible. Other [35] ant species have more chromosomes.

Spider mite Jack jumper ant Myrmecia pilosula

414 2

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 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," says Jan 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. 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

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 DNArepair 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 GNTHER1 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. Speakman Aberdeen Centre for Energy regulation and Obesity (ACERO), School of Biological Sciences, University of Aberdeen,Aberdeen AB24 2TZ, Scotland, UK -mail: peakman@abdn.ac.uk Accepted 23 February 2005