Challenges in Developing Geroscience Trials

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Aug 19

PMID 37598227

Authors

Yves Rolland

Felipe Sierra

Luigi Ferrucci

Nir Barzilai

Rafael de Cabo

Joan Mannick

Anthony Oliva

William Evans

Davide Angioni

Philipe De Souto Barreto

Jeremy Raffin

Bruno Vellas

James L Kirkland

Affiliations

Soon will be listed here.

Abstract

Geroscience is becoming a major hope for preventing age-related diseases and loss of function by targeting biological mechanisms of aging. This unprecedented paradigm shift requires optimizing the design of future clinical studies related to aging in humans. Researchers will face a number of challenges, including ideal populations to study, which lifestyle and Gerotherapeutic interventions to test initially, selecting key primary and secondary outcomes of such clinical trials, and which age-related biomarkers are most valuable for both selecting interventions and predicting or monitoring clinical responses ("Gerodiagnostics"). This article reports the main results of a Task Force of experts in Geroscience.

Citing Articles

Roadmap for alleviating the manifestations of ageing in the cardiovascular system.

Liberale L, Tual-Chalot S, Sedej S, Ministrini S, Georgiopoulos G, Grunewald M Nat Rev Cardiol. 2025; .

PMID: 39972009 DOI: 10.1038/s41569-025-01130-5.

The bioavailability and blood levels of low-dose rapamycin for longevity in real-world cohorts of normative aging individuals.

Harinath G, Lee V, Nyquist A, Moel M, Wouters M, Hagemeier J Geroscience. 2025; .

PMID: 39873920 DOI: 10.1007/s11357-025-01532-w.

Hallmarks of aging: middle-aging hypovascularity, tissue perfusion and nitric oxide perspective on healthspan.

Phua T Front Aging. 2025; 5():1526230.

PMID: 39839443 PMC: 11747043. DOI: 10.3389/fragi.2024.1526230.

Deep learning and generative artificial intelligence in aging research and healthy longevity medicine.

Wilczok D Aging (Albany NY). 2025; 17(1):251-275.

PMID: 39836094 PMC: 11810058. DOI: 10.18632/aging.206190.

Mikhail 'Misha' Blagosklonny's enduring legacy in geroscience: the hyperfunction theory and the therapeutic potential of rapamycin.

Barzilai D Aging (Albany NY). 2025; 17(1):1-15.

PMID: 39808121 PMC: 11810056. DOI: 10.18632/aging.206189.

References

Shoemaker M, Curtis A, Vangsnes E, Dickinson M . Clinically meaningful change estimates for the six-minute walk test and daily activity in individuals with chronic heart failure. Cardiopulm Phys Ther J. 2013; 24(3):21-9. PMC: 3751711. View

Wissler Gerdes E, Misra A, Espindola Netto J, Tchkonia T, Kirkland J . Strategies for late phase preclinical and early clinical trials of senolytics. Mech Ageing Dev. 2021; 200:111591. PMC: 8627448. DOI: 10.1016/j.mad.2021.111591. View

Martyanov V, Kim G, Hayes W, Du S, Ganguly B, Sy O . Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease. PLoS One. 2017; 12(11):e0187580. PMC: 5679625. DOI: 10.1371/journal.pone.0187580. View

Rudnicka E, Napierala P, Podfigurna A, Meczekalski B, Smolarczyk R, Grymowicz M . The World Health Organization (WHO) approach to healthy ageing. Maturitas. 2020; 139:6-11. PMC: 7250103. DOI: 10.1016/j.maturitas.2020.05.018. View

Naylor R, Baker D, Van Deursen J . Senescent cells: a novel therapeutic target for aging and age-related diseases. Clin Pharmacol Ther. 2012; 93(1):105-16. PMC: 4051295. DOI: 10.1038/clpt.2012.193. View

Gonzales M, Garbarino V, Marques Zilli E, Petersen R, Kirkland J, Tchkonia T . Senolytic Therapy to Modulate the Progression of Alzheimer's Disease (SToMP-AD): A Pilot Clinical Trial. J Prev Alzheimers Dis. 2022; 9(1):22-29. PMC: 8612719. DOI: 10.14283/jpad.2021.62. View

Seals D, Justice J, LaRocca T . Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J Physiol. 2015; 594(8):2001-24. PMC: 4933122. DOI: 10.1113/jphysiol.2014.282665. View

Thompson W, Hornby B, Manuel R, Bradley E, Laux J, Carr J . A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Genet Med. 2020; 23(3):471-478. PMC: 7935714. DOI: 10.1038/s41436-020-01006-8. View

Onder G, Penninx B, Balkrishnan R, Fried L, Chaves P, Williamson J . Relation between use of angiotensin-converting enzyme inhibitors and muscle strength and physical function in older women: an observational study. Lancet. 2002; 359(9310):926-30. DOI: 10.1016/s0140-6736(02)08024-8. View

10.

Guida J, Agurs-Collins T, Ahles T, Campisi J, Dale W, Demark-Wahnefried W . Strategies to Prevent or Remediate Cancer and Treatment-Related Aging. J Natl Cancer Inst. 2020; 113(2):112-122. PMC: 7850536. DOI: 10.1093/jnci/djaa060. View

11.

Chiasson J, Josse R, Gomis R, Hanefeld M, Karasik A, Laakso M . Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA. 2003; 290(4):486-94. DOI: 10.1001/jama.290.4.486. View

12.

Tchkonia T, Kirkland J . Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic Strategies. JAMA. 2018; 320(13):1319-1320. DOI: 10.1001/jama.2018.12440. View

13.

Justice J, Miller J, Newman J, Hashmi S, Halter J, Austad S . Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes. J Gerontol A Biol Sci Med Sci. 2016; 71(11):1415-1423. PMC: 5055651. DOI: 10.1093/gerona/glw126. View

14.

Ness K, Armstrong G, Kundu M, Wilson C, Tchkonia T, Kirkland J . Frailty in childhood cancer survivors. Cancer. 2014; 121(10):1540-7. PMC: 4424063. DOI: 10.1002/cncr.29211. View

15.

Hong J, Zhang Y, Lai S, Lv A, Su Q, Dong Y . Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2012; 36(5):1304-11. PMC: 3631843. DOI: 10.2337/dc12-0719. View

16.

Tavassoli N, De Souto Barreto P, Berbon C, Mathieu C, de Kerimel J, Lafont C . Implementation of the WHO integrated care for older people (ICOPE) programme in clinical practice: a prospective study. Lancet Healthy Longev. 2022; 3(6):e394-e404. DOI: 10.1016/S2666-7568(22)00097-6. View

17.

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

18.

Tchkonia T, Palmer A, Kirkland J . New Horizons: Novel Approaches to Enhance Healthspan Through Targeting Cellular Senescence and Related Aging Mechanisms. J Clin Endocrinol Metab. 2020; 106(3):e1481-e1487. PMC: 7947756. DOI: 10.1210/clinem/dgaa728. View

19.

Franceschi C, Garagnani P, Morsiani C, Conte M, Santoro A, Grignolio A . The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Front Med (Lausanne). 2018; 5:61. PMC: 5890129. DOI: 10.3389/fmed.2018.00061. View

20.

Heerspink H, Stefansson B, Correa-Rotter R, Chertow G, Greene T, Hou F . Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020; 383(15):1436-1446. DOI: 10.1056/NEJMoa2024816. View