Maximum life span

Maximum life span (or, for

Most living species have an upper limit on the number of times somatic cells not expressing telomerase can divide. This is called the Hayflick limit, although this number of cell divisions does not strictly control lifespan.

Definition

In animal studies, maximum span is often taken to be the

Demographic evidence

The longest living person whose dates of birth and death were verified according to the modern norms of Guinness World Records and the Gerontology Research Group was Jeanne Calment (1875–1997), a Frenchwoman who is verified to have lived to 122. The oldest male lifespan has only been verified as 116, by Japanese man Jiroemon Kimura. Reduction of infant mortality has accounted for most of the increased average life span longevity, but since the 1960s mortality rates among those over 80 years have decreased by about 1.5% per year. "The progress being made in lengthening lifespans and postponing senescence is entirely due to medical and public-health efforts, rising standards of living, better education, healthier nutrition and more salubrious lifestyles."^[4] Animal studies suggest that further lengthening of median human lifespan as well as maximum lifespan could be achieved through "calorie restriction mimetic" drugs or by directly reducing food consumption.^[5] Although calorie restriction has not been proven to extend the maximum human life span as of 2014^[update], results in ongoing primate studies have demonstrated that the assumptions derived from rodents are valid in primates.^[6][7]

It has been proposed that no fixed theoretical limit to human longevity is apparent today.^[8][9] Studies in the biodemography of human longevity indicate a late-life mortality deceleration law: that death rates level off at advanced ages to a late-life mortality plateau. That is, there is no fixed upper limit to human longevity, or fixed maximal human lifespan.^[10] This law was first quantified in 1939, when researchers found that the one-year probability of death at advanced age asymptotically approaches a limit of 44% for women and 54% for men.^[11]

However, this evidence depends on the existence of a late-life plateaus and deceleration that can be explained, in humans and other species, by the existence of very rare errors.^[12][13] Age-coding error rates below 1 in 10,000 are sufficient to make artificial late-life plateaus, and errors below 1 in 100,000 can generate late-life mortality deceleration. These error rates cannot be ruled out by examining documents^[13] (the standard) because of successful pension fraud, identity theft, forgeries and errors that leave no documentary evidence. This capacity for errors to explain late-life plateaus solves the "fundamental question in aging research is whether humans and other species possess an immutable life-span limit" and suggests that a limit to human life span exists.^[14] A theoretical study suggested the maximum human lifespan to be around 125 years using a modified stretched exponential function for human survival curves.^[15] In another study, researchers claimed that there exists a maximum lifespan for humans, and that the human maximal lifespan has been declining since the 1990s.^[16] A theoretical study also suggested that the maximum human life expectancy at birth is limited by the human life characteristic value δ, which is around 104 years.^[17]

In 2017, the United Nations conducted a Bayesian sensitivity analysis of global population burden based on life expectancy projection at birth in future decades. The 95% prediction interval of average life expectancy rises as high as 106 years old by 2090, with ongoing and layered effects on world population and demography should that happen. However, the prediction interval is extremely wide.^[18]

Non-demographic evidence

Evidence for maximum lifespan is also provided by the dynamics of physiological indices with age. For example, scientists have observed that a person's

In animals

Small animals such as birds and squirrels rarely live to their maximum life span, usually dying of accidents, disease or predation.

The maximum life span of most species is documented in the AnAge repository (The Animal Ageing and Longevity Database).^[22]

Maximum life span is usually longer for species that are larger or have effective defenses against predation, such as bird flight,^[23] chemical defenses^[24] or living in social groups.^[25]

The differences in life span between species demonstrate the role of genetics in determining maximum life span ("rate of aging"). The records (in years) are these:

• for common house mouse, 4^[26]
• for Brown rat, 3.8^[27]
• for
  List of oldest dogs)^[28]
• for cats, 38 (See List of oldest cats)^[29]
• for common cranes, 43^[30]
• for polar bears, 42^[31] (Debby)
• for horses, 62^[32]
• for Asian elephants, 86^[33]

The longest-lived vertebrates have been variously described as

• Large parrots (macaws and cockatoos can live up to 80–100 years in captivity)
• Koi (a Japanese species of fish, allegedly living up to 200 years, though generally not exceeding 50 – a specimen named Hanako was reportedly 226 years old upon her death)^[34][35]
• Tortoises (Seychelles tortoise) (192 years)^[36]
• Tuatara (a New Zealand reptile species, 100–200+ years^[37])
• Eels, the so-called Brantevik Eel (Swedish: Branteviksålen) is thought to have lived in a water well in southern Sweden since 1859, which makes it over 150 years old.^[38] It was reported that it had died in August 2014 at an age of 155.^[39]
• amino acids, has indicated a maximum life span of "177 to 245 years old".^[41][42][43]
• Greenland sharks are currently the vertebrate species with the longest known lifespan.^[44] An examination of 28 specimens in one study published in 2016 determined by radiocarbon dating that the oldest of the animals that they sampled had lived for about 392 ± 120 years (a minimum of 272 years and a maximum of 512 years). The authors further concluded that the species reaches sexual maturity at about 150 years of age.^[44]

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:

• A bivalve mollusk (Arctica islandica) (aka "Ming", lived 507±2 years.^[45][46])

Exceptions

• Some jellyfish species, including Turritopsis dohrnii, Laodicea undulata,^[47] and Aurelia sp.1,^[48] are able to revert to the polyp stage even after reproducing (so-called reversible life cycle), rather than dying as in other jellyfish. Consequently, these species are considered biologically immortal and have no maximum lifespan.^[49]
• There may be no natural limit to the Hydra's life span, but it is not yet clear how to estimate the age of a specimen.
• cellular division.^[50]
• Lobsters are sometimes said to be biologically immortal because they do not seem to slow down, weaken, or lose fertility with age. However, due to the energy needed for moulting, they cannot live indefinitely.^[51]

"Maximum life span" here means the mean life span of the most long-lived 10% of a given cohort. Caloric restriction has not yet been shown to break mammalian world records for longevity.

Accumulated DNA damage appears to be a limiting factor in the determination of maximum life span. The theory that DNA damage is the primary cause of aging, and thus a principal determinant of maximum life span, has attracted increased interest in recent years. This is based, in part, on evidence in humans and mice that inherited deficiencies in DNA repair genes often cause accelerated aging.^[59][60][61] There is also substantial evidence that DNA damage accumulates with age in mammalian tissues, such as those of the brain, muscle, liver, and kidney (reviewed by Bernstein et al.^[62] and see DNA damage theory of aging and DNA damage (naturally occurring)). One expectation of the theory (that DNA damage is the primary cause of aging) is that among species with differing maximum life spans, the capacity to repair DNA damage should correlate with lifespan. The first experimental test of this idea was by Hart and Setlow^[63] who measured the capacity of cells from seven different mammalian species to carry out DNA repair. They found that nucleotide excision repair capability increased systematically with species longevity. This correlation was striking and stimulated a series of 11 additional experiments in different laboratories over succeeding years on the relationship of nucleotide excision repair and life span in mammalian species (reviewed by Bernstein and Bernstein^[64]). In general, the findings of these studies indicated a good correlation between nucleotide excision repair capacity and life span. The association between nucleotide excision repair capability and longevity is strengthened by the evidence that defects in nucleotide excision repair proteins in humans and rodents cause features of premature aging, as reviewed by Diderich.^[60]

Further support for the theory that DNA damage is the primary cause of aging comes from study of

• A comparison of the heart
  cardiac output^[66]
• For mammals there is a direct relationship between mitochondrial membrane fatty acid saturation and maximum life span^[67]
• Studies of the liver lipids of mammals and a bird (pigeon) show an inverse relationship between maximum life span and number of double bonds^[68]
• Selected species of birds and mammals show an inverse relationship between telomere rate of change (shortening) and maximum life span^[69]
• Maximum life span correlates negatively with antioxidant enzyme levels and free-radicals production and positively with rate of DNA repair^[70]
• Female mammals express more Mn−SOD and glutathione peroxidase antioxidant enzymes than males. This has been hypothesized as the reason they live longer^[71] However, mice entirely lacking in glutathione peroxidase 1 do not show a reduction in lifespan.
• The maximum life span of transgenic mice has been extended about 20% by overexpression of human catalase targeted to mitochondria^[72]
• 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^[73]
• A study of 8 non-primate mammals showed an inverse correlation between maximum life span and oxidative damage to mtDNA (mitochondrial DNA) in heart & brain^[74]
• A study of several species of mammals and a bird (pigeon) indicated a linear relationship between oxidative damage to protein and maximum life span^[75]
• There is a direct correlation between DNA repair and maximum life span for mammalian species^[76]
• 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^[77]
• Overexpression of the enzyme which synthesizes glutathione in long-lived transgenic Drosophila (fruit-flies) extended maximum lifespan by nearly 50%^[78]
• A mutation in the age−1 gene of the
  mean life span 65% and maximum life span 110%.^[79]
  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%.^[80]
• 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.^[81]
• Short-term induction of
  mitohormesis.^[82]

• Extreme longevity tracking
• Genetics of aging
• Longevity quotient
• Strategies for engineered negligible senescence (SENS)

References