longevity
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Introduction
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]
- 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:
- sequence variant spectrum comparable to non-supercentenarian genomes
- well-established human longevity variants were not found
- comparable number of disease-associated variants relative to most human genomes sequenced to-date
- ~1% of the variants these individuals possess are novel & may point to new genes involved in exceptional longevity
- 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]
- four or more children by age 30
- farmer
- slim or medium body build
- taller height marginally associated
Personality traits of men associated with better longevity
- openness to new experiences
- conscientiousness
- BMI > 25 in elderly women associated with diminished mortality[9]
- no relationship between BMI & mortality in elderly men[9]
- higher higher muscle mass associated with increased longevity among older adults[27]
Management
Means to extend healthy life span:
- diet is the most effective means
- Mediterranean diet & DASH diet associated with benefit[31]
- the MIND diet is a composite of the two
- calorie restriction extends maximum life span in rodents, yeast[2]
- calorie restriction extends mean life span & delays onset of age-associated pathologies in rhesus monkeys, including diabetes, cancer, cardiovascular disease, & brain atrophy[6]
- calorie restriction appears to exert its effects via Sirt1 activity in the hypothalamus[26]
- neither blueberry, pomegranate, green tea, black tea, cinnamon, sesame, pycnogenol & taxifolin), curcumin, morin, or quercetin extends life span of mice[24]
- very low meat diet may increase life expectancy[25]
- Mediterranean diet & DASH diet associated with benefit[31]
- life style modification
- 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]
- not smoking
- alcohol especially red wine, or not at all
- rich social environment[22][30]
- engaging in mental, social, physical, & productive leisure
- healthy body mass index[37]
- healthy lifestyle is associated with longer life expectancy among men & women, & a larger percentage of their life without Alzheimer's dementia[46]
- exercise
- pharmaceuticals & nutraceuticals are the most lucrative
- high-dose resveratrol mitigates delterious effects of high-calorie, high-fat diet in mice[3]
- rapamycin increases longevity in mice probaby via inhibition of mTOR[5]
- antioxidants (vitamin A, vitamin C, vitamin E) of no benefit
- no pharmaceutical/nutraceutical ready for clinical implementation
- feeling younger than your actual age may increase longevity[28]
- social integration associated with living longer[35]
- 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]
More general terms
More specific terms
Additional terms
- aging
- centenarian
- healthy (successful) aging; sustained independence
- human longevity protein
- life expectancy
- mortality
- prevention of cognitive impairment
- supercentenarian
References
- ↑ Netscape News cites Associated Press
- ↑ 2.0 2.1 Weindruch R and Walford RL, The retardation of aging and disease by dietary restriction. Charles C Thomas, Springfield IL, 1988
Guarente L, Picard F. Calorie restriction--the SIR2 connection. Cell. 2005 Feb 25;120(4):473-82. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15734680 - ↑ 3.0 3.1 Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. Resveratrol improves health and survival of mice on a high- calorie diet. Nature. 2006 Nov 1; [Epub ahead of print] <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/17086191 <Internet> http://dx.doi.org/10.1038/nature05354
- ↑ 4.0 4.1 Barzilai N et al, A genotype of exceptional longevity is associated with preservation of cognitive function. Neurology 2006, 67:2170 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17190939
- ↑ 5.0 5.1 Gavrilov L & Gavrilova N University of Chicago's Center on Aging Gerontological Society of America annual meeting, San Francisco, CA Nov 19, 2007 (per NetScape)
- ↑ 6.0 6.1 Colman RJ et al Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 2009 Jul 10; 325:201. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19590001
- ↑ Miller T Proceedings of the 38th Annual Meeting of the American Aging Association: Integrative Biology: Hormones, Signaling, and Aging. May 29-June 1, 2009, Scottsdale, AZ
Harrison DE et al Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009 Jul 8 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/19587680 <Internet> http://dx.doi.org/10.1038/nature08221 - ↑ 8.0 8.1 Taylor MD et al Five factor model personality traits and all-cause mortality in the Edinburgh Artery Study cohort. Psychosom Med 2009 May 28 http://dx.doi.org/10.1097/PSY.0b013e3181a65298 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19483118
- ↑ 9.0 9.1 9.2 Stessman J et al Normal body mass index rather than obesity predicts greater mortality in elderly people: The Jerusalem Longitudinal Study. J Am Geriatr Soc 2009 Dec; 57:2232 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19925614
- ↑ 10.0 10.1 10.2 Li Y et al Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet. 2009 Dec 15;18(24):4897-904. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19793722
- ↑ 11.0 11.1 Di Cianni F et al MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case-control study using a multilocus genotyping. Age (Dordr). 2012 May 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22576335
- ↑ 12.0 12.1 Benigni A et al Variations of the angiotensin II type 1 receptor gene are associated with extreme human longevity. Age (Dordr). 2012 May 9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22569962
- ↑ 13.0 13.1 Soerensen M. Genetic variation and human longevity. Dan Med J. 2012 May;59(5):B4454. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22549493
- ↑ 14.0 14.1 Kerber RA et ak A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional loci. PLoS One. 2012;7(4):e34746. Epub 2012 Apr 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22506048
- ↑ 15.0 15.1 Lai JY et al Family history of exceptional longevity is associated with lower serum uric acid levels in Ashkenazi Jews. J Am Geriatr Soc. 2012 Apr;60(4):745-50 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22429185
- ↑ 16.0 16.1 Sebastiani P et al Whole genome sequences of a male and female supercentenarian, ages greater than 114 years. Front Genet. 2011;2:90. Epub 2012 Jan 3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22303384
- ↑ 17.0 17.1 17.2 Sebastiani P et al Genetic signatures of exceptional longevity in humans. PLoS One. 2012;7(1):e29848. Epub 2012 Jan 18. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22279548
- ↑ 18.0 18.1 Soerensen M et al Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22234866
- ↑ 19.0 19.1 Yamakuchi M MicroRNA Regulation of SIRT1. Front Physiol. 2012;3:68. Epub 2012 Mar 30. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22479251
- ↑ 20.0 20.1 Passtoors WM Transcriptional profiling of human familial longevity indicates a role for ASF1A and IL7R. PLoS One. 2012;7(1):e27759. Epub 2012 Jan 11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22247756
- ↑ 21.0 21.1 Katzmarzyk PT and Lee I-M. Sedentary behavior and life expectancy in the USA: A cause- deleted life table analysis. BMJ Open 2012 Jul 9; 2:e000828 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22777603
- ↑ 22.0 22.1 Rizzuto D et al. Lifestyle, social factors, and survival after age 75: Population based study. BMJ 2012 Aug 30; 345:e5568 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22936786
- ↑ 23.0 23.1 Mangelsdorf D, Zhang Y, Kliewer S The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. elife. 2012;1:e00065. Epub 2012 Oct 15. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23066506
- ↑ 24.0 24.1 Spindler S, Mote PL, Flegal JM, Teter B. Influence on longevity of blueberry, cinnamon, green and black tea, pomegranate, sesame, curcumin, morin, Pycnogenol, quercetin and taxifolin fed isocalorically to long-lived, outcrossed mice. Rejuvenation Res. 2013 Feb 24. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23432089
- ↑ 25.0 25.1 Singh PN, Sabate J, Fraser GE. Does low meat consumption increase life expectancy in humans? Am J Clin Nutr. 2003 Sep;78(3 Suppl):526S-532S. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12936945
- ↑ 26.0 26.1 Satoh A, Brace CS, Rensing N et al Sirt1 Extends Life Span and Delays Aging in Mice through the Regulation of Nk2 Homeobox 1 in the DMH and LH. Cell Metab. 2013 Sep 3;18(3):416-30 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24011076
- ↑ 27.0 27.1 Srikanthan P and Karlamangla AS. Muscle mass index as a predictor of longevity in older adults. Am J Med 2014 Jun; 127:547 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24561114
- ↑ 28.0 28.1 Rippon I, Steptoe A Feeling Old vs Being Old. Associations Between Self-perceived Age and Mortality. JAMA Intern Med. Published online December 15, 2014 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25506678 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2020288
- ↑ GBD 2013 DALYs and HALE Collaborators, Murray CJ et al Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990-2013: quantifying the epidemiological transition. Lancet. Aug 26, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26321261 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2961340-X/abstract
- ↑ 30.0 30.1 Larzelere MM, Campbell J, Adu-Sarkodie NY. Psychosocial factors in aging. Clin Geriatr Med. 2011;27:645-660. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22062446
- ↑ 31.0 31.1 Mathers JC. Impact of nutrition on the ageing process. Br J Nutr. 2015;113:S18-S22. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25415221
- ↑ Paganini-Hill A, Kawas C, Corrada M. Antioxidant vitamin intake and mortality: the Leisure World Cohort Study. Am J Epidemiol. 2015;181:120-126 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25550360
- ↑ 33.0 33.1 Puterman E, Gemmill A, Karasek D et al. Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study. Proc Natl Acad Sci U S A 2016 Oct 3; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27698131 Free Article
- ↑ 34.0 34.1 Chen BH, Marioni RE, Colicino E et al. DNA methylation-based measures of biological age: Meta-analysis predicting time to death. Aging (Albany NY) 2016 Sep 28; 8:1844. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27690265 Free Article
- ↑ 35.0 35.1 Hobbs WR et al. Online social integration is associated with reduced mortality risk. Proc Natl Acad Sci U S A 2016 Nov 15; 113:12980 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27799553 Free PMC Article
- ↑ 36.0 36.1 Khan SS, Shah SJ, Klyachko E et al A null mutation in SERPINE1 protects against biological aging in humans. Science Advances. 15 Nov 2017:Vol. 3, no. 11, eaao1617 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29152572 Free PMC Article <Internet> http://advances.sciencemag.org/content/3/11/eaao1617.full
- ↑ 37.0 37.1 37.2 Li Y, Pan A, Wang DD et al Impact of Healthy Lifestyle Factors on Life Expectancies in the US Population. Circulation. April 30, 2018 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29712712 <Internet> http://circ.ahajournals.org/content/early/2018/04/25/CIRCULATIONAHA.117.032047
- ↑ 38.0 38.1 Mandsager K, Harb S, Cremer P et al. Association of cardiorespiratory fitness with long-term mortality among adults undergoing exercise treadmill testing. JAMA Netw Open 2018 Oct 19; 1:e183605 Not indexed in PubMed https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2707428
- ↑ 39.0 39.1 Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
- ↑ 40.0 40.1 Lee LO, James P, Zevon ES et al. Optimism is associated with exceptional longevity in 2 epidemiologic cohorts of men and women. Proc Natl Acad Sci U S A 2019 Sep 10; 116:18357. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31451635 https://www.pnas.org/content/116/37/18357
- ↑ 41.0 41.1 Hoenig MC, Willscheid N, Bischof GN et al Assessment of Tau Tangles and Amyloid-beta Plaques Among Super Agers Using PET Imaging. JAMA Netw Open. 2020;3(12):e2028337. Dec 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33306113 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2774071
- ↑ 42.0 42.1 Gefen T, Kawles A, Makowski-Woidan B et al Paucity of Entorhinal Cortex Pathology of the Alzheimer's Type in SuperAgers with Superior Memory Performance. Cerebral Cortex. 2021. Feb 17 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33592091 https://academic.oup.com/cercor/advance-article/doi/10.1093/cercor/bhaa409/6137893
- ↑ Samuelson K Next step in Alzheimer's research: Brain shrinkage rates. SuperAger brains shrink more slowly than peers' brains. Northwestern Now. April 04, 2017 https://news.northwestern.edu/stories/2017/april/alzheimers-research-superagers-brain-shrinkage/
Cook AH, Sridhar J, Ohm D et al Rates of Cortical Atrophy in Adults 80 Years and Older With Superior vs Average Episodic Memory JAMA. 2017;317(13):1373-1375 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28384819 <Internet> http://jamanetwork.com/journals/jama/article-abstract/2614177 - ↑ 44.0 44.1 Harrison L People Who Live Past 100 Have Good DNA Repair Genes. Medscape - Jun 01, 2021. https://www.medscape.com/viewarticle/952117
Garagnani P, Marquis J, Delledonne M et al eLife 2021;10:e57849. May 4. https://elifesciences.org/articles/57849 - ↑ 45.0 45.1 Finegood ED, Briley DQ, Turiano NA et al Association of Wealth With Longevity in US Adults at Midlife. JAMA Health Forum. 2021;2(7):e211652 Not indexed in PubMed https://jamanetwork.com/journals/jama-health-forum/fullarticle/2782410
- ↑ 46.0 46.1 George J Longevity Without Alzheimer's Tied to Lifestyle. More years of life did not mean more years with dementia. MedPage Today April 13, 20 https://www.medpagetoday.com/neurology/alzheimersdisease/98199
Dhana K, Evans DA, Rajan KB et al Healthy lifestyle and the risk of Alzheimer dementia. Findings from 2 longitudinal studies. Neurology. 2020 95(4) July 28 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32554763 PMCID: PMC7455318 Free PMC article https://n.neurology.org/content/95/4/e374
Dhana K, Franco OH, Ritz EM et al Healthy lifestyle and life expectancy with and without Alzheimer's dementia: population based cohort study. BMJ. 2022 Apr 13;377:e068390 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35418416 - ↑ 47.0 47.1 Gorzelitz J, Trabert B, Katki HA et al Independent and joint associations of weightlifting and aerobic activity with all- cause, cardiovascular disease and cancer mortality in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Br J Sports Med. 2022. Sep 27;bjsports-2021-105315 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/36167669 <Internet> http://press.psprings.co.uk/bjsm/september/bjsm105315.pdf
- ↑ 48.0 48.1 Melville NA Pumping Iron Improves Longevity in Older Adults. Medscape. October 07, 2022 https://www.medscape.com/viewarticle/982033
- ↑ 49.0 49.1 Webber BJ, Piercy KL, Hyde ET et al Association of Muscle-Strengthening and Aerobic Physical Activity With Mortality in US Adults Aged 65 Years or Older. JAMA Netw Open. 2022;5(10):e2236778. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36251297 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797402
- ↑ 50.0 50.1 Optimism linked to longevity and well-being in two recent studies. National Institute on Aging. Dec 8, 2022 https://www.nia.nih.gov/news/optimism-linked-longevity-and-well-being-two-recent-studies
Koga HK, Trudel-Fitzgerald C, Lee LO et al. Optimism, lifestyle, and longevity in a racially diverse cohort of women. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35674052 PMCID: PMC9588526 Free PMC article https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.17897
Lee LO, Grodstein F, Trudel-Fitzgerald C et al. Optimism, daily stressors, and emotional well-being over two decades in a cohort of aging men. J Gerontol B Psychol Sci Soc Sci. 2022 Aug 11;77(8):1373-1383 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35255123 PMCID: PMC9371455 (available on 2023-03-07) - ↑ DeVito LM, Barzilai N, Cuervo AM et al Extending human healthspan and longevity: a symposium report. Ann N Y Acad Sci. 2022 Jan;1507(1):70-83 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34498278 https://nyaspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/nyas.14681
- ↑ 52.0 52.1 Lopez-Bueno R et al. Prospective associations of different combinations of aerobic and muscle- strengthening activity with all-cause, cardiovascular, and cancer mortality. JAMA Intern Med 2023 Sep; 183:982-990. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37548973 PMCID: PMC10407764 (available on 2024-08-07) https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2807854
- ↑ 53.0 53.1 53.2 Brooks-Wilson AR. Genetics of healthy aging and longevity. Hum Genet. 2013 Dec;132(12):1323-38. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23925498 PMCID: PMC3898394 Free PMC article. Review.