Maximum life span

Maximum life span is a measure of the maximum number of years a member of a group has been observed to survive. Maximum life span literally corresponds to the age at which the oldest known member of a species or experimental group has died, or the current age of the oldest living member, if higher. Maximum life span is contrasted to mean life span (average lifespan or life expectancy). Mean life span varies with susceptibility to disease, accident, suicide and homicide, whereas maximum life span is determined by "rate of aging". Epistemologically maximum life span also depends upon initial sample size. In animal studies, maximum life span is typically taken to be the mean life span of the most long-lived 10% of a given cohort. This may be taken to be "definition 2" of 'maximum life span.'

Overview
The oldest recognized person on record is Jeanne Calment, a Frenchwoman who lived for 122 years and 164 days. Maximum life span for humans has remained about 115&minus;120 calendar years throughout recorded history, despite steady improvements in life expectancy. Reduction of infant mortality has accounted for most of this increased average longevity, but since the 1960s mortality rates among those over 80 years has decreased by about 1.5% per year. Advances in medicine, calorie restriction with adequate nutrition, or other interventions are said to have slowed the aging process, but have not been proven to extend the maximum human life span (see below). This information has led to a hypothesis that the human body may have some sort of automatic "shut-off" switch, and it will get to a point where, no matter how healthy an individual has remained, their bodies simply cannot go on any longer.

The maximum life span of each species is different. These differences demonstrate the role of genetics in determining maximum life span ("rate of aging"). The records are: The longest-lived vertebrates have been variously described as
 * for mice, 4;
 * for dogs, 29;
 * for cats, 38;
 * for goldfish, 49
 * for horses, 62;
 * for elephants, 78;
 * for humans, 122.5
 * tortoises (Galápagos tortoise) (193 years)
 * whales (Bowhead Whale) (about 210 years)

Non-vertebrate species that continue to grow (i.e. clams, coral) can live hundreds of years, such as:


 * bivalve mollusks (Icelandic Cyprine) (374 years)

Plants tend to come in annuals, biennials, and perennials. The longer-lived perennials, woody-stemmed plants such as trees and bushes, often live for hundreds and even thousands of years (one may question whether or not they may die of old age). A giant sequoia, General Sherman is alive and well in its second millenary. A Great Basin Bristlecone Pine is almost 5000 years (4844 years), and Prometheus was even older, more than 5000 years.

Although considered fiction for a time, recent research has indicated that bowhead whales recently killed still had harpoons in their bodies from the 1790s, which, along with analysis of amino acids, has indicated a maximum life span so far of 211 years. Birds and squirrels rarely live to their maximum life span, usually dying of accidents and disease. Grazing animals show wear-and-tear to their teeth to the point where they can no longer eat, and they die of starvation.

The maximum life span of most species has not been accurately determined because the data collection has been minimal and the number of species studied in captivity (or by monitoring in the wild) has been small. Maximum life span is usually longer for species that are larger, can fly and have larger brains. Of the approximately 20,000 to 25,000 genes in the human genome, it is estimated that only 2% of these are different from those of a chimpanzee, which has an average lifespan of 52 years. The difference in longevity could be due to as few as a hundred genes or less, however there may be other factors which influence the life span of chimpanzees.

Identical twins tend to die within 3 years of each other, whereas fraternal twins tend to die within 6 years. Aging theories associated with DNA include programmed aging (or programmed aging-resistance) and theories that link aging with DNA damage/mutation or DNA repair capability.

Increasing maximum life span
Currently, the only (non-transgenic) method of increasing maximum life span that is recognized by biogerontologists is calorie restriction with adequate nutrition. However, this is true only if we use definition 2 of maximum life span, as caloric restriction has not yet been shown to break mammalian world records for longevity. Rats, mice and hamsters experience maximum life span extension from a diet which contains 40&minus;60% of the calories (but all of the required nutrients) which the animals consume when they can eat as much as they want. Mean life span is increased 65% and maximum life span is increased 50%, when calorie restriction is begun just before puberty. (For a recent review of maximum life span extension by calorie restriction in rodent studies, see GENES & DEVELOPMENT; Koubova,J; 17(3):313-321 (2003) ). For fruit flies the life extending benefits of calorie restriction are gained immediately at any age upon beginning calorie restriction and ended immediately at any age upon resuming full feeding SCIENCE; Mair,W; 301:1731-1733 (2003) ].

Mammals fed anti-oxidants show up to a 30% increase in mean life span, but no increase in maximum life span. Antioxidants are most valuable for animals that are cancer-prone, or subjected to radiation or chemical toxins. There are evidently homeostatic mechanisms in cells that govern the amount of allowable antioxidant activity. Many life-extensionists have dismissed the value of antioxidants simply because they have not been shown to increase maximum life span, but such a view neglects the significance of an extended mean life span.

Many transgenic species of mice have been created which have maximum life span greater than that of wild-type or laboratory mice, including Ames dwarf mice, Snell dwarf mice, mice with increased mitochondrial catalase, and others.

Some biomedical gerontologists (gerontologists who search for ways to extend maximum life span) believe that biomedical molecular engineering can someday extend maximum lifespan and even bring about rejuvenation.

One such researcher is Aubrey de Grey, who calls his project to reverse the damage we call aging SENS (Strategies for Engineered Negligible Senescence). Dr. de Grey has established the The Methuselah Mouse Prize to award money to researchers who can extend the maximum life span of mice.

Research data concerning maximum life span

 * A comparison of the heart mitochondria in rats (4-year maximum life span) and pigeons (35-year maximum life span) showed that pigeon mitochondria leak fewer free-radicals than rat mitochondria, despite the fact that both animals have similar metabolic rate and cardiac output


 * For mammals there is a direct relationship between mitochondrial membrane fatty acid saturation and maximum life span


 * Studies of the liver lipids of mammals and a bird (pigeon) show an inverse relationship between maximum life span and number of double bonds


 * Selected species of birds and mammals show an inverse relationship between telomere rate of change (shortening) and maximum life span


 * Maximum life span correlates negatively with antioxidant enzyme levels and correlates positively with lower rate of free-radicals production and higher rate of DNA repair


 * Females express both more Mn&minus;SOD and more glutathione peroxidase antioxidant enzymes than males, and this has been suggested to be the reason females live longer than males in mammalian species


 * The maximum life span of transgenic mice has been extended about 20% by overexpression of human catalase targeted to mitochondria


 * A comparison of 7 non-primate mammals (mouse, hamster, rat, guinea-pig, rabbit, pig and cow) showed that the rate of mitochondrial superoxide and hydrogen peroxide production in heart and kidney were inversely correlated with maximum life span


 * A study of 8 non-primate mammals showed a direct correlation between maximum life span and oxidative damage to mtDNA (mitochondrial DNA) in heart & brain


 * A study of several species of mammals and a bird (pigeon) indicated a linear relationship between oxidative damage to protein and maximum life span


 * There is a direct correlation between DNA repair and maximum life span for mammalian species


 * Drosophila (fruit-flies) bred for 15 generations by only using eggs that were laid toward the end of reproductive life achieved maximum life spans 30% greater than that of controls


 * Overexpression of the enzyme which synthesizes glutathione in long-lived transgenic Drosophila (fruit-flies) extended maximum lifespan by nearly 50%


 * A mutation in the age&minus;1 gene of the nematode worm Caenorhabditis elegans increased mean life span 65% and maximum life span 110%


 * Fat-specific Insulin Receptor KnockOut (FIRKO) mice have reduced fat mass, normal calorie intake and an increased maximum life span of 18%


 * The capacity of mammalian species to detoxify the carcinogenic chemical benzo(a)pyrene to a water-soluble form also correlates well with maximum life span