Maximum life span explained
Maximum life span is a measure of the maximum amount of time one or more members of a group has been observed to survive between birth and death.
In animal studies, maximum life span is often taken to be the mean life span of the most long-lived 10% of a given cohort. By another definition, however, maximum life span corresponds to the age at which the oldest known member of a species or experimental group has died. Calculation of the maximum life span in the former sense depends upon initial sample size.
Maximum life span is in contrast with mean life span (average life span 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".
The oldest recognized person on record is Jeanne Calment, a French woman who lived for 122 years and 164 days. Maximum recorded life span for humans has remained about 105-122 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 have 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. Although calorie restriction has not been proven to extend the maximum human life span, as of 2006, results in ongoing primate studies are promising .
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.
In other animals
Small animals such as 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 or have effective defenses against predation, such as bird flight, tortoise shells, porcupine quills, or large primate brains. When compared to primates, of the approximately 20,000 to 25,000 genes in the human genome, it is estimated that 6% of these are different from those of a chimpanzee which has an average lifespan of only 52 years, in contrast to the human lifespan. The difference in longevity between humans and chimps could be due to as few as a hundred genes or less; however there may be other factors that shorten the life span of chimpanzees.
The differences between life span between species demonstrate the role of genetics in determining maximum life span ("rate of aging"). The records (in years) are these:
The longest-lived vertebrates have been variously described as
Although this idea was considered specious 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 at least 211 years  .
Invertebrate species which continue to grow as long as they live (e.g., certain clams, some coral species) can on occasion live hundreds of years:
However, with the possible exception of the Bowhead whale, the claims of lifespans >100 year must be taken with some skepticisms as they rely on conjecture (e.g. counting otoliths) rather than empirical, continuous documentation.
Plants are referred to as annuals which only live one year, biennials which live two years, and perennials which live longer than that. The longest-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 millennium. A Great Basin Bristlecone Pine called Methuselah is 4,838 years old and the Bristlecone Pine called Prometheus was a little older still, 4,844 years, when it was cut down in 1964.
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. "Maximum life span" here means the mean life span of the most long-lived 10% of a given cohort, 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 that contains 40–60% of the calories (but all of the required nutrients) that 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 caloric restriction is begun just before puberty.). 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).
Mammals fed antioxidants show up to a 30% increase in mean life span, but no increase in maximum life span (though even that is controversial: many studies report no increase in lifespan at all). 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.
A few transgenic species of mice have been created that have maximum life spans greater than that of wild-type or laboratory mice. The Ames and Snell mice, which have mutations in pituitary transcription factors and hence are deficient in Gh, LH, TSH, and secondarly IGF1, have extensions in maximal lifespan of up to 65%. To date, both in absolute and relative terms, these Ames and Snell mice have the maximum lifespan of any mouse not on caloric restriction (see below on GhR). Mutations/knockout of other genes affecting the GH/IGF1 axis, such as Lit, Ghr and Irs1 have also shown extension in lifespan, but much more modest both in relative and absolute terms. The longest ever lived laboratory mouse was a Ghr knockout on caloric restriction, which lived to ~1800 days (maximum for normal B6 mice under ideal conditions is 1200 days) in the lab of A. Bartke at Southern Illinois University.
Most biomedical gerontologists (gerontologists who search for ways to extend maximum life span) believe that biomedical molecular engineering will eventually extend maximum lifespan and even bring about rejuvenation.
While most aging researchers are rather cautious, fearing a vitalist public backlash, one theoretical gerontologist not shy of expressing opinions on the extension of human lifespan is Aubrey de Grey. His theoretical project to reverse the damage called aging is called 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. A. Bartker collected the prize for the GhR knockout mouse and Speakman collected the prize for extending the maximum lifespan of an adult mouse, using caloric restriction initiated late in lifespan.
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-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 This theory is difficult to square with the fact that mice lacking Glutathione peroxidase 1 entirely do not show any reduction in lifespan whatsoever.
- 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-1 gene of the nematode worm Caenorhabditis elegans increased mean life span 65% and maximum life span 110% . However, the degree of lifespan extension in relative terms by both the age-1 and daf-2 mutations is strongly dependent on ambient temperature, with ~10% extension at 16*C and 65% extension at 27*C.
- 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
- Short-term induction of oxidative stress due to calorie restriction increases life span in Caenorhabditis elegans by promoting stress defense, specifically by inducing an enzyme called catalase. As shown by Michael Ristow and co-workers nutritive antioxidants completely abolish this extension of life span by inhibiting a process called mitohormesis. 
Notes and References
- [Leonid A. Gavrilov]
- Jane E. Brody (Tuesday, August 26, 2008) "Living Longer, in Good Health to the End", New York Times p. D7, is an article on compression of morbidity: adults can be vigorous well into their 80s, with their illnesses and disabilities compressed into a short period before their deaths.
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