Turning Back Time with Emerging Rejuvenation Strategies

Overview

Journal Nat Cell Biol

Specialty Cell Biology

Date 2019 Jan 4

PMID 30602763

Citations 78

Authors

Salah Mahmoudi

Lucy Xu

Anne Brunet

Affiliations

Soon will be listed here.

Abstract

Ageing is associated with the functional decline of all tissues and a striking increase in many diseases. Although ageing has long been considered a one-way street, strategies to delay and potentially even reverse the ageing process have recently been developed. Here, we review four emerging rejuvenation strategies-systemic factors, metabolic manipulations, senescent cell ablation and cellular reprogramming-and discuss their mechanisms of action, cellular targets, potential trade-offs and application to human ageing.

Citing Articles

A comparative study of metformin and nicotinamide riboside in alleviating tissue aging in rats.

Geng L, Zhang B, Liu H, Wang S, Cai Y, Yang K Life Med. 2025; 2(1):lnac045.

PMID: 39872949 PMC: 11749560. DOI: 10.1093/lifemedi/lnac045.

Uncoupling of mTORC1 from E2F activity maintains DNA damage and senescence.

Daigh L, Saha D, Rosenthal D, Ferrick K, Meyer T Nat Commun. 2024; 15(1):9181.

PMID: 39448567 PMC: 11502682. DOI: 10.1038/s41467-024-52820-6.

A cellular identity crisis? Plasticity changes during aging and rejuvenation.

Gorelov R, Hochedlinger K Genes Dev. 2024; 38(17-20):823-842.

PMID: 39293862 PMC: 11535162. DOI: 10.1101/gad.351728.124.

Non-pharmaceutical interventions and epigenetic aging in adults: Protocol for a scoping review.

Liebich A, Zheng S, Schachner T, Mair J, Jovanova M, Muller-Riemenschneider F PLoS One. 2024; 19(8):e0301763.

PMID: 39159141 PMC: 11332928. DOI: 10.1371/journal.pone.0301763.

Cell autocloning as a pathway to their real rejuvenation.

Salnikov L Front Aging. 2024; 5:1429156.

PMID: 39136004 PMC: 11317467. DOI: 10.3389/fragi.2024.1429156.

References

Lopez-Otin C, Blasco M, Partridge L, Serrano M, Kroemer G . The hallmarks of aging. Cell. 2013; 153(6):1194-217. PMC: 3836174. DOI: 10.1016/j.cell.2013.05.039. View

Kennedy B, Berger S, Brunet A, Campisi J, Cuervo A, Epel E . Geroscience: linking aging to chronic disease. Cell. 2014; 159(4):709-13. PMC: 4852871. DOI: 10.1016/j.cell.2014.10.039. View

Kenyon C . The genetics of ageing. Nature. 2010; 464(7288):504-12. DOI: 10.1038/nature08980. View

Gems D, Partridge L . Genetics of longevity in model organisms: debates and paradigm shifts. Annu Rev Physiol. 2012; 75:621-44. DOI: 10.1146/annurev-physiol-030212-183712. View

Brandhorst S, Choi I, Wei M, Cheng C, Sedrakyan S, Navarrete G . A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015; 22(1):86-99. PMC: 4509734. DOI: 10.1016/j.cmet.2015.05.012. View

Cheng C, Villani V, Buono R, Wei M, Kumar S, Yilmaz O . Fasting-Mimicking Diet Promotes Ngn3-Driven β-Cell Regeneration to Reverse Diabetes. Cell. 2017; 168(5):775-788.e12. PMC: 5357144. DOI: 10.1016/j.cell.2017.01.040. View

Cerletti M, Jang Y, Finley L, Haigis M, Wagers A . Short-term calorie restriction enhances skeletal muscle stem cell function. Cell Stem Cell. 2012; 10(5):515-9. PMC: 3561899. DOI: 10.1016/j.stem.2012.04.002. View

Newman J, Covarrubias A, Zhao M, Yu X, Gut P, Ng C . Ketogenic Diet Reduces Midlife Mortality and Improves Memory in Aging Mice. Cell Metab. 2017; 26(3):547-557.e8. PMC: 5605815. DOI: 10.1016/j.cmet.2017.08.004. View

Roberts M, Wallace M, Tomilov A, Zhou Z, Marcotte G, Tran D . A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metab. 2017; 26(3):539-546.e5. PMC: 5609489. DOI: 10.1016/j.cmet.2017.08.005. View

10.

Harrison D, Strong R, Sharp Z, Nelson J, Astle C, Flurkey K . Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009; 460(7253):392-5. PMC: 2786175. DOI: 10.1038/nature08221. View

11.

Longo V, Antebi A, Bartke A, Barzilai N, Brown-Borg H, Caruso C . Interventions to Slow Aging in Humans: Are We Ready?. Aging Cell. 2015; 14(4):497-510. PMC: 4531065. DOI: 10.1111/acel.12338. View

12.

de Cabo R, Carmona-Gutierrez D, Bernier M, Hall M, Madeo F . The search for antiaging interventions: from elixirs to fasting regimens. Cell. 2014; 157(7):1515-26. PMC: 4254402. DOI: 10.1016/j.cell.2014.05.031. View

13.

Conboy M, Conboy I, Rando T . Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging Cell. 2013; 12(3):525-30. PMC: 4072458. DOI: 10.1111/acel.12065. View

14.

de Keizer P . The Fountain of Youth by Targeting Senescent Cells?. Trends Mol Med. 2017; 23(1):6-17. DOI: 10.1016/j.molmed.2016.11.006. View

15.

Mahmoudi S, Brunet A . Aging and reprogramming: a two-way street. Curr Opin Cell Biol. 2012; 24(6):744-56. PMC: 3540161. DOI: 10.1016/j.ceb.2012.10.004. View

16.

Brack A, Conboy M, Roy S, Lee M, Kuo C, Keller C . Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science. 2007; 317(5839):807-10. DOI: 10.1126/science.1144090. View

17.

Conboy I, Conboy M, Wagers A, Girma E, Weissman I, Rando T . Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. 2005; 433(7027):760-4. DOI: 10.1038/nature03260. View

18.

Loffredo F, Steinhauser M, Jay S, Gannon J, Pancoast J, Yalamanchi P . Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell. 2013; 153(4):828-39. PMC: 3677132. DOI: 10.1016/j.cell.2013.04.015. View

19.

Baht G, Silkstone D, Vi L, Nadesan P, Amani Y, Whetstone H . Exposure to a youthful circulaton rejuvenates bone repair through modulation of β-catenin. Nat Commun. 2015; 6:7131. PMC: 4479006. DOI: 10.1038/ncomms8131. View

20.

Sinha M, Jang Y, Oh J, Khong D, Wu E, Manohar R . Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle. Science. 2014; 344(6184):649-52. PMC: 4104429. DOI: 10.1126/science.1251152. View