Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 May:59:101037.
doi: 10.1016/j.arr.2020.101037. Epub 2020 Feb 25.

The road ahead for health and lifespan interventions

Marta Gonzalez-Freire  1 , Alberto Diaz-Ruiz  2 , David Hauser  3 , Jorge Martinez-Romero  4 , Luigi Ferrucci  3 , Michel Bernier  3 , Rafael de Cabo  3
Affiliations
Review

The road ahead for health and lifespan interventions

Marta Gonzalez-Freire et al. Ageing Res Rev. 2020 May.

Abstract

Aging is a modifiable risk factor for most chronic diseases and an inevitable process in humans. The development of pharmacological interventions aimed at delaying or preventing the onset of chronic conditions and other age-related diseases has been at the forefront of the aging field. Preclinical findings have demonstrated that species, sex and strain confer significant heterogeneity on reaching the desired health- and lifespan-promoting pharmacological responses in model organisms. Translating the safety and efficacy of these interventions to humans and the lack of reliable biomarkers that serve as predictors of health outcomes remain a challenge. Here, we will survey current pharmacological interventions that promote lifespan extension and/or increased healthspan in animals and humans, and review the various anti-aging interventions selected for inclusion in the NIA's Interventions Testing Program as well as the ClinicalTrials.gov database that target aging or age-related diseases in humans.

Keywords: Aging; Frailty; Healthspan; Lifespan; Longevity; Translation; “anti-aging”.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest The authors declare no conflicts of interest, financial or otherwise.

Figures

Fig. 1.
Fig. 1.. Hallmarks of aging and the four domains of aging phenotypes.
Integrative view of the hallmarks of aging described by Lopez-Otin et al. (2013) and the domains of the aging phenotypes described by Ferrucci et al. (2010). Different factors (genes, environment, exercise and nutrition) contribute to the rate of biological aging. The loss of reserve capacity or resilience, at a molecular and cellular level, ultimately leads to the development of the aging phenotypes.
Fig. 2.
Fig. 2.. Compounds tested by the National Institute on Aging (NIA) Interventions Testing Program (ITP) for their anti-aging activity and effects on lifespan extension in mice.
Some compounds elicit anti-aging effects on lifespan that are sex-dependent. For instance, rapamycin and acarbose extend lifespan in both sexes whereas methylene blue (in red) has pro-longevity effects only in females. Four compounds (in blue) extend lifespan in males. Most of the compounds are still being tested and there is no data available.
Fig. 3.
Fig. 3.. Heatmap summarizing the different interventions and their effect in maximum and mean lifespan extension in mice.
These interventions target major signaling pathways whose dysregulation contributes to the emergence of the aging phenotypes and disease.
Fig. 4.
Fig. 4.. Personalized approach for the treatment of age and age-related diseases.
The identification of relevant biomarkers of healthspan and the integration of ‘omics’ data sets from the genome, transcriptome, proteome, and metabolome, and machine learning approaches, will likely allow the development of personalized treatments aimed at reducing age-related diseases.
See this image and copyright information in PMC

References

    1. Ables GP, Johnson JE, 2017. Pleiotropic responses to methionine restriction. Exp. Gerontol. 94, 83–88. 10.1016/j.exger.2017.01.012. - DOI - PubMed
    1. Alavez S, Vantipalli MC, Zucker DJS, Klang IM, Lithgow GJ, 2011. Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan. Nature 472, 226–229. 10.1038/nature09873. - DOI - PMC - PubMed
    1. Alfaras I, Mitchell SJ, Mora H, Lugo DR, Warren A, Navas-Enamorado I, Hoffmann V, Hine C, Mitchell JR, Le Couteur DG, Cogger VC, Bernier M, de Cabo R, 2017. Health benefits of late-onset metformin treatment every other week in mice. NPJ Aging Mech. Dis. 3, 16 10.1038/s41514-017-0018-7. - DOI - PMC - PubMed
    1. Allard JS, Perez EJ, Fukui K, Carpenter P, Ingram DK, de Cabo R, 2016. Prolonged metformin treatment leads to reduced transcription of Nrf2 and neurotrophic factors without cognitive impairment in older C57BL/6J mice. Behav. Brain Res. 301, 1–9. 10.1016/j.bbr.2015.12.012. - DOI - PMC - PubMed
    1. Alvers AL, Fishwick LK, Wood MS, Hu D, Chung HS, Dunn WAJ, Aris JP, 2009. Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae. Aging Cell 8, 353–369. 10.1111/j.1474-9726.2009.00469.x. - DOI - PMC - PubMed

Publication types