Literature DB >> 30906924

Development of Clinical Trials to Extend Healthy Lifespan.

Jamie N Justice1, Laura Niedernhofer2, Paul D Robbins2, Vanita R Aroda3, Mark A Espeland4, Stephen B Kritchevsky1, George A Kuchel5, Nir Barzilai6.   

Abstract

Significant progress in defining the biology of aging, particularly in animal models, supports the geroscience hypothesis, which posits that by therapeutically targeting biological aging, the onset of multiple age-related diseases can be delayed "en suite". Geroscience investigators are preparing to test this hypothesis in humans for the first time. In this review, we describe development of large-scale clinical trials designed to determine if multiple age-related health conditions can be simultaneously alleviated with interventions targeting the underlying biology of aging. We describe the rationale and collaborative, consensus building approach used to design the first aging outcomes trial called Targeting Aging with Metformin (TAME). Through this case study, we outline features that could be more broadly extended to other geroscience-guided clinical trials, including a process for selecting biochemical and molecular markers of biologic age and we provide a perspective on the potential impact of clinical trials targeting aging.

Entities:  

Keywords:  aging; biomarkers; clinical trials; geroscience; healthspan; multi-morbidity

Year:  2018        PMID: 30906924      PMCID: PMC6428447          DOI: 10.1097/XCE.0000000000000159

Source DB:  PubMed          Journal:  Cardiovasc Endocrinol Metab        ISSN: 2574-0954


  31 in total

1.  Extending the lifespan of long-lived mice.

Authors:  A Bartke; J C Wright; J A Mattison; D K Ingram; R A Miller; G S Roth
Journal:  Nature       Date:  2001-11-22       Impact factor: 49.962

2.  Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice.

Authors:  Joanne S Allard; Evelyn J Perez; Koji Fukui; Priscilla Carpenter; Donald K Ingram; Rafael de Cabo
Journal:  Behav Brain Res       Date:  2015-12-14       Impact factor: 3.332

3.  Clinical Trials Targeting Aging and Age-Related Multimorbidity.

Authors:  Mark A Espeland; Eileen M Crimmins; Brandon R Grossardt; Jill P Crandall; Jonathan A L Gelfond; Tamara B Harris; Stephen B Kritchevsky; JoAnn E Manson; Jennifer G Robinson; Walter A Rocca; Marinella Temprosa; Fridtjof Thomas; Robert Wallace; Nir Barzilai
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2017-03-01       Impact factor: 6.053

4.  Senotherapeutics for healthy ageing.

Authors:  Laura J Niedernhofer; Paul D Robbins
Journal:  Nat Rev Drug Discov       Date:  2018-04-13       Impact factor: 84.694

5.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.

Authors:  William C Knowler; Elizabeth Barrett-Connor; Sarah E Fowler; Richard F Hamman; John M Lachin; Elizabeth A Walker; David M Nathan
Journal:  N Engl J Med       Date:  2002-02-07       Impact factor: 91.245

Review 6.  Interventions to Slow Aging in Humans: Are We Ready?

Authors:  Valter D Longo; Adam Antebi; Andrzej Bartke; Nir Barzilai; Holly M Brown-Borg; Calogero Caruso; Tyler J Curiel; Rafael de Cabo; Claudio Franceschi; David Gems; Donald K Ingram; Thomas E Johnson; Brian K Kennedy; Cynthia Kenyon; Samuel Klein; John J Kopchick; Guenter Lepperdinger; Frank Madeo; Mario G Mirisola; James R Mitchell; Giuseppe Passarino; Karl L Rudolph; John M Sedivy; Gerald S Shadel; David A Sinclair; Stephen R Spindler; Yousin Suh; Jan Vijg; Manlio Vinciguerra; Luigi Fontana
Journal:  Aging Cell       Date:  2015-04-22       Impact factor: 9.304

7.  Strategies and Challenges in Clinical Trials Targeting Human Aging.

Authors:  John C Newman; Sofiya Milman; Shahrukh K Hashmi; Steve N Austad; James L Kirkland; Jeffrey B Halter; Nir Barzilai
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2016-08-16       Impact factor: 6.053

Review 8.  Molecular and physiological manifestations and measurement of aging in humans.

Authors:  Sadiya S Khan; Benjamin D Singer; Douglas E Vaughan
Journal:  Aging Cell       Date:  2017-05-23       Impact factor: 9.304

9.  Senolytics improve physical function and increase lifespan in old age.

Authors:  Ming Xu; Tamar Pirtskhalava; Joshua N Farr; Bettina M Weigand; Allyson K Palmer; Megan M Weivoda; Christina L Inman; Mikolaj B Ogrodnik; Christine M Hachfeld; Daniel G Fraser; Jennifer L Onken; Kurt O Johnson; Grace C Verzosa; Larissa G P Langhi; Moritz Weigl; Nino Giorgadze; Nathan K LeBrasseur; Jordan D Miller; Diana Jurk; Ravinder J Singh; David B Allison; Keisuke Ejima; Gene B Hubbard; Yuji Ikeno; Hajrunisa Cubro; Vesna D Garovic; Xiaonan Hou; S John Weroha; Paul D Robbins; Laura J Niedernhofer; Sundeep Khosla; Tamara Tchkonia; James L Kirkland
Journal:  Nat Med       Date:  2018-07-09       Impact factor: 53.440

10.  Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males.

Authors:  David E Harrison; Randy Strong; David B Allison; Bruce N Ames; Clinton M Astle; Hani Atamna; Elizabeth Fernandez; Kevin Flurkey; Martin A Javors; Nancy L Nadon; James F Nelson; Scott Pletcher; James W Simpkins; Daniel Smith; J Erby Wilkinson; Richard A Miller
Journal:  Aging Cell       Date:  2013-11-19       Impact factor: 9.304

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  22 in total

Review 1.  Genetics of extreme human longevity to guide drug discovery for healthy ageing.

Authors:  Zhengdong D Zhang; Sofiya Milman; Jhih-Rong Lin; Shayne Wierbowski; Haiyuan Yu; Nir Barzilai; Vera Gorbunova; Warren C Ladiges; Laura J Niedernhofer; Yousin Suh; Paul D Robbins; Jan Vijg
Journal:  Nat Metab       Date:  2020-07-27

2.  Testing the Geroscience Hypothesis: Early Days.

Authors:  Stephen B Kritchevsky; Jamie N Justice
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2020-01-01       Impact factor: 6.053

3.  Commentary: rapamycin for the aging skin.

Authors:  Christian Sell
Journal:  Geroscience       Date:  2020-03-29       Impact factor: 7.713

Review 4.  The central moTOR of metabolism.

Authors:  Judith Simcox; Dudley W Lamming
Journal:  Dev Cell       Date:  2022-03-21       Impact factor: 12.270

5.  SARS-CoV-2, COVID-19 and the Ageing Immune System.

Authors:  Juliet M Bartleson; Dina Radenkovic; Anthony J Covarrubias; David Furman; Daniel A Winer; Eric Verdin
Journal:  Nat Aging       Date:  2021-09-14

6.  Considerations Regarding Public Use of Longevity Interventions.

Authors:  Yasmine J Liu; Rebecca L McIntyre; Georges E Janssens
Journal:  Front Aging       Date:  2022-04-25

Review 7.  Bring Back the Rat!

Authors:  Christy S Carter; Arlan Richardson; Derek M Huffman; Steven Austad
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2020-02-14       Impact factor: 6.053

Review 8.  No Time to Age: Uncoupling Aging from Chronological Time.

Authors:  Dana Larocca; Jieun Lee; Michael D West; Ivan Labat; Hal Sternberg
Journal:  Genes (Basel)       Date:  2021-04-21       Impact factor: 4.096

Review 9.  Autophagy and the hallmarks of aging.

Authors:  Susmita Kaushik; Inmaculada Tasset; Esperanza Arias; Olatz Pampliega; Esther Wong; Marta Martinez-Vicente; Ana Maria Cuervo
Journal:  Ageing Res Rev       Date:  2021-09-24       Impact factor: 10.895

Review 10.  Frailty and HIV: Moving from Characterization to Intervention.

Authors:  Kristine M Erlandson; Damani A Piggott
Journal:  Curr HIV/AIDS Rep       Date:  2021-04-05       Impact factor: 5.495

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