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longevity

In reference to a long life. Also see aging & healthy aging. See supercentenarian for World's oldest living persons. Pathology: - cerebral cortical atrophy occurs slower in elderly >= 80 years of age with preserved episodic memory [8] - longevity with unimpaired cognition into old age is associated with resistance to development of neurofibrillary tangles & senile plaques - normal aging is associated with isolated neurofibrillary tangles [41] - resistance to age-related neurofibrillary degeneration in the entorhinal cortex may contribute to preserved memory in SuperAgers. [42] Genetics: Genetic contributions to longevity: - heritability of age at death in adulthood is ~25 % [53] - longevity locus on chromosome 3 [53] - other putative longevity loci differ between studies - VV genotype (I450V) of CETP gene in humans promotes longevity & is protective against cognitive decline [4,17] - polymorphism(s) in SIRT1 may be associated with longevity [19] - SNPs of FOXO1A are associated with longevity in women [10] - SNPs of FOXO3A are associated with longevity in both men & women [10] - SNPs in intron 1 of MAP3K7 & intron 1 of GSTZ1 are associatedwith longevity [11] - two polymorphisms in AGTR1 promoter, in complete linkage disequilibrium are associated with human longevity [12] - polymorphism(s) in TERT may be associated with human longevity [13] - polymorphism(s) in APOE may be associated with human longevity [17] - polymorphism(s) in IL6 may be associated with human longevity [18] - human longevity is linked to chromosome 3p24.1 (gene unknown) [14] - lower serum uric acid levels in Ashkenazi Jews associated with longevity [15] - diminished expression of ASF1A & IL7R associated with longevity [20] - increased expression of FGF-21 may be associated with longevity [23] - heterozygousity of null SERPINE1 allele associated with longevity [36] - DNA repair mechanisms protecting against mutations in STK17A &/or COA1 or the region between the genes may play a role [44] - complete genomic sequences of male & female supercentenarians, both age > 114 years reveal: a) sequence variant spectrum comparable to non-supercentenarian genomes b) well-established human longevity variants were not found c) comparable number of disease-associated variants relative to most human genomes sequenced to-date d) ~1% of the variants these individuals possess are novel & may point to new genes involved in exceptional longevity e) both individuals are enriched for coding variants near longevity-associated variants [16] - individual genetic variants associated with longevity have weak effects, but specific combinations may have strong effects [39] - see human longevity protein for protein products of genes with SNPs found disportionately in persons with extreme longevity - telomere length [33] & DNA methylation patterns [34] have been proposed to predict life span Clinical manifestations: Characteristics of American men favoring achieving centenarian status [5] 1) four or more children by age 30 2) farmer 3) slim or medium body build 4) taller height marginally associated Personality traits of men associated with better longevity 1) openness to new experiences 2) conscientiousness Body mass index (BMI) 1) BMI > 25 in elderly women associated with diminished mortality [9] 2) no relationship between BMI & mortality in elderly men [9] 3) higher higher muscle mass associated with increased longevity among older adults [27] Management: Means to extend healthy life span: 1) diet is the most effective means a) Mediterranean diet & DASH diet associated with benefit [31] - the MIND diet is a composite of the two b) calorie restriction extends maximum life span in rodents, yeast [2] c) calorie restriction extends mean life span & delays onset of age-associated pathologies in rhesus monkeys, including diabetes, cancer, cardiovascular disease, & brain atrophy [6] d) calorie restriction appears to exert its effects via Sirt1 activity in the hypothalamus [26] e) neither blueberry, pomegranate, green tea, black tea, cinnamon, sesame, pycnogenol & taxifolin), curcumin, morin, or quercetin extends life span of mice [24] f) very low meat diet may increase life expectancy [25] 2) life style modification a) exercise - recommendations vary, 30 minutes/day [37] - sitting daily for <3 hours & watching TV for <2 hours extends life expectancy by ~ 1-2 years [21] - life expectancy increases as aerobic fitness improves with no upper limit of benefit at any age [38] - combination of aerobic exercise & weightlifting associated with 47-50% lower all-cause mortality risk in adults [47,52] - regular weightlifting with or without moderate to vigorous aerobic activity reduces all-cause & cardiovascular disease mortality, albeit less than combination of aerobic exercise & weightlifting [48] - leisure time muscle-strengthening exercise & moderate to vigorous aerobic exercise re independently associated with lower all-cause mortality US adults >= 65 years of age [49] b) not smoking c) alcohol especially red wine, or not at all d) rich social environment [22,30] - engaging in mental, social, physical, & productive leisure e) healthy body mass index [37] f) healthy lifestyle is associated with longer life expectancy among men & women, & a larger percentage of their life without Alzheimer's dementia [46] 3) pharmaceuticals & nutraceuticals are the most lucrative a) high-dose resveratrol mitigates delterious effects of high-calorie, high-fat diet in mice [3] b) rapamycin increases longevity in mice probaby via inhibition of mTOR[5] c) antioxidants (vitamin A, vitamin C, vitamin E) of no benefit d) no pharmaceutical/nutraceutical ready for clinical implementation 4) feeling younger than your actual age may increase longevity [28] 5) social integration associated with living longer [35] 6) optimism associated with living > 85 years [40] - optimism associated with longevity in women & well-being in men [50] Notes: - net worth at midlife may be associated with longevity [45]

Related

aging centenarian healthy (successful) aging; sustained independence human longevity protein life expectancy mortality prevention of cognitive impairment supercentenarian

Specific

evolutionary biology of longevity pharmaceutical extension of longevity

General

gerontology

References

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