TY - JOUR
T1 - Longevity and lifespan control in mammals
T2 - Lessons from the mouse
AU - Chen, Yi Fan
AU - Wu, Chia Yu
AU - Kao, Cheng Heng
AU - Tsai, Ting Fen
N1 - Funding Information:
We acknowledge support from the National Science Council (NSC97-2320-B-010-015-MY3), the Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, and a grant from the Ministry of Education, Aim for the Top University Plan.
PY - 2010/11
Y1 - 2010/11
N2 - Aging, which affects all organ systems, is one of the most complex phenotypes. Recent discoveries in long-lived mutant mice have revealed molecular mechanisms of longevity in mammals which may contribute to our understanding of why humans age. These mutations include naturally occurring spontaneous mutations, and those of mice genetically modified by modern genomic technologies. It is generally believed that the most fundamental mechanisms of aging are evolutionarily conserved across species. The following types of longevity mechanisms have been intensively studied: suppression of the somatotropic (growth hormone/insulin-like growth factor 1) axis, decreased metabolism and increased resistance of oxidative stress, reduced insulin secretion and increased insulin sensitivity, and delayed reproductive maturation and reduced fertility. In addition, many of the mutations have a sex-dependent effect on lifespan, and when present in different genetic backgrounds, the effects of the same gene mutation can vary considerably. The present review discusses these phenotypic variations as well as describing the known longevity genes in long-lived mutant mice and the molecular mechanisms specifying longevity. We anticipate that these mouse studies will ultimately provide clues about how to delay the aging and prolong lifespan, and help to develop therapies for healthier human aging.
AB - Aging, which affects all organ systems, is one of the most complex phenotypes. Recent discoveries in long-lived mutant mice have revealed molecular mechanisms of longevity in mammals which may contribute to our understanding of why humans age. These mutations include naturally occurring spontaneous mutations, and those of mice genetically modified by modern genomic technologies. It is generally believed that the most fundamental mechanisms of aging are evolutionarily conserved across species. The following types of longevity mechanisms have been intensively studied: suppression of the somatotropic (growth hormone/insulin-like growth factor 1) axis, decreased metabolism and increased resistance of oxidative stress, reduced insulin secretion and increased insulin sensitivity, and delayed reproductive maturation and reduced fertility. In addition, many of the mutations have a sex-dependent effect on lifespan, and when present in different genetic backgrounds, the effects of the same gene mutation can vary considerably. The present review discusses these phenotypic variations as well as describing the known longevity genes in long-lived mutant mice and the molecular mechanisms specifying longevity. We anticipate that these mouse studies will ultimately provide clues about how to delay the aging and prolong lifespan, and help to develop therapies for healthier human aging.
KW - Aging
KW - Lifespan
KW - Long-lived mice
KW - Longevity
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U2 - 10.1016/j.arr.2010.07.003
DO - 10.1016/j.arr.2010.07.003
M3 - Review article
C2 - 20667513
AN - SCOPUS:77957937648
VL - 9
SP - S28-S35
JO - Ageing Research Reviews
JF - Ageing Research Reviews
SN - 1568-1637
IS - SUPPL.
ER -