Life-extending interventions do not necessarily result in compression of morbidity: a case example offering a robust statistical approach

Fries JF. The compression of morbidity: near or far? Milbank Q. 1989;67(2):208–32. https://doi.org/10.2307/3350138.

Article  CAS  PubMed  Google Scholar 

Fries JF. The compression of morbidity. Milbank Q. 1983;83(4):801–23. https://doi.org/10.1111/j.1468-0009.2005.00401.x.

Article  Google Scholar 

Manuel DG, Schultz SE, Kopec JA. Measuring the health burden of chronic disease and injury using health adjusted life expectancy and the health utilities index. J Epidemiol Community Health. 2002;56(11):843–50. https://doi.org/10.1136/jech.56.11.843.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yamada Y, Kemnitz JW, Weindruch R, Anderson RM, Schoeller DA, Colman RJ. Caloric restriction and healthy life span: frail phenotype of nonhuman primates in the Wisconsin National Primate Research Center Caloric Restriction Study. J Gerontol A Biol Sci Med Sci. 2017;73(3):273–8. https://doi.org/10.1093/gerona/glx059.

Article  PubMed Central  Google Scholar 

Mattison JA, Colman RJ, Beasley TM, Allison DB, Kemnitz JW, Roth GS, et al. Caloric restriction improves health and survival of rhesus monkeys. Nat Commun. 2017;8(1):14063. https://doi.org/10.1038/ncomms14063.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009;325(5937):201–4. https://doi.org/10.1126/science.1173635.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD, Neumann-Haefelin E, et al. TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab. 2012;15(5):713–24. https://doi.org/10.1016/j.cmet.2012.04.007.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460(7253):392–5. https://doi.org/10.1038/nature08221.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bitto A, Ito TK, Pineda VV, LeTexier NJ, Huang HZ, Sutlief E, et al. Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice. Elife. 2016;5:e16351. https://doi.org/10.7554/eLife.16351.

Article  PubMed  PubMed Central  Google Scholar 

Alfaras I, Mitchell SJ, Mora H, Lugo DR, Warren A, Navas-Enamorado I, et al. Health benefits of late-onset metformin treatment every other week in mice. NPJ Aging Mech Dis. 2017;3(1):16. https://doi.org/10.1038/s41514-017-0018-7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, et al. Metformin improves healthspan and lifespan in mice. Nat Commun. 2013;4:2192. https://doi.org/10.1038/ncomms3192.

Article  CAS  PubMed  Google Scholar 

Strong R, Miller RA, Antebi A, Astle CM, Bogue M, Denzel MS, et al. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell. 2016;15(5):872–84. https://doi.org/10.1111/acel.12496.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harrison DE, Strong R, Allison DB, Ames BN, Astle CM, Atamna H, et al. Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell. 2014;13(2):273–82. https://doi.org/10.1111/acel.12170.

Article  CAS  PubMed  Google Scholar 

Miller RA, Harrison DE, Allison DB, Bogue M, Debarba L, Diaz V, et al. Canagliflozin extends life span in genetically heterogeneous male but not female mice. JCI Insight. 2020. https://doi.org/10.1172/jci.insight.140019.

Article  PubMed  PubMed Central  Google Scholar 

Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun. 2019;10(1):5284. https://doi.org/10.1038/s41467-019-13172-8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kirkland JL, Tchkonia T, Zhu Y, Niedernhofer LJ, Robbins PD. The clinical potential of senolytic drugs. J Am Geriatr Soc. 2017;65(10):2297–301. https://doi.org/10.1111/jgs.14969.

Article  PubMed  PubMed Central  Google Scholar 

Xu Q, Fu Q, Li Z, Liu H, Wang Y, Lin X, et al. The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice. Nat Metab. 2021;3(12):1706–26. https://doi.org/10.1038/s42255-021-00491-8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yousefzadeh MJ, Zhu Y, McGowan SJ, Angelini L, Fuhrmann-Stroissnigg H, Xu M, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18–28. https://doi.org/10.1016/j.ebiom.2018.09.015.

Article  PubMed  PubMed Central  Google Scholar 

Xu M, Pirtskhalava T, Farr JN, Weigand BM, Palmer AK, Weivoda MM, et al. Senolytics improve physical function and increase lifespan in old age. Nat Med. 2018;24(8):1246–56. https://doi.org/10.1038/s41591-018-0092-9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tain LS, Jain C, Nespital T, Froehlich J, Hinze Y, Grönke S, et al. Longevity in response to lowered insulin signaling requires glycine N-methyltransferase-dependent spermidine production. Aging Cell. 2020;19(1):e13043. https://doi.org/10.1111/acel.13043.

Article  CAS  PubMed  Google Scholar 

Eisenberg T, Knauer H, Schauer A, Büttner S, Ruckenstuhl C, Carmona-Gutierrez D, et al. Induction of autophagy by spermidine promotes longevity. Nat Cell Biol. 2009;11(11):1305–14. https://doi.org/10.1038/ncb1975.

Article  CAS  PubMed  Google Scholar 

Doeppner TR, Coman C, Burdusel D, Ancuta D-L, Brockmeier U, Pirici DN, et al. Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism. Aging. 2022;14(10):4195–210. https://doi.org/10.18632/aging.204069.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li W, Zou Z, Cai Y, Yang K, Wang S, Liu Z, et al. Low-dose chloroquine treatment extends the lifespan of aged rats. Protein Cell. 2022;13(6):454–61. https://doi.org/10.1007/s13238-021-00903-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Alle Q, Le Borgne E, Bensadoun P, Lemey C, Béchir N, Gabanou M, et al. A single short reprogramming early in life initiates and propagates an epigenetically related mechanism improving fitness and promoting an increased healthy lifespan. Aging Cell. 2022;21(11):e13714. https://doi.org/10.1111/acel.13714.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fischer KE, Hoffman JM, Sloane LB, Gelfond JA, Soto VY, Richardson AG, et al. A cross-sectional study of male and female C57BL/6Nia mice suggests lifespan and healthspan are not necessarily correlated. Aging. 2016;8(10):2370. https://doi.org/10.18632/aging.101059.

Article  PubMed  PubMed Central  Google Scholar 

Garmany A, Terzic A. Global healthspan-lifespan gaps among 183 World Health Organization member states. JAMA Netw Open. 2024;7(12):e2450241-e. https://doi.org/10.1001/jamanetworkopen.2024.50241.

Article  Google Scholar 

Manton KG, Gu X, Lowrimore GR. Cohort changes in active life expectancy in the US elderly population: experience from the 1982–2004 national long-term care survey. J Gerontol B Psychol Sci Soc Sci. 2008;63(5):S269–81. https://doi.org/10.1093/geronb/63.5.S269.

Comments (0)

No login
gif