The quest to slow ageing through drug discovery
Open accessAbstract
Although death is inevitable, individuals have long sought to alter the course of the ageing process. Indeed, ageing has proved to be modifiable; by intervening in biological systems, such as nutrient sensing, cellular senescence, the systemic environment and the gut microbiome, phenotypes of ageing can be slowed sufficiently to mitigate age-related functional decline. These interventions can also delay the onset of many disabling, chronic diseases, including cancer, cardiovascular disease and neurodegeneration, in animal models. Here, we examine the most promising interventions to slow ageing and group them into two tiers based on the robustness of the preclinical, and some clinical, results, in which the top tier includes rapamycin, senolytics, metformin, acarbose, spermidine, NAD+ enhancers and lithium. We then focus on the potential of the interventions and the feasibility of conducting clinical trials with these agents, with the overall aim of maintaining health for longer before the end of life.
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Attenuation of age-related inflammation is a common mechanism by which pharmacological interventions into ageing exert their beneficial effects.
“Indeed, attenuation of age-related inflammation has emerged as a common mechanism by which (pharmacological) interventions into ageing exert their beneficial effects4.”
From cGAS–STING drives ageing-related inflammation and neurodegeneration (2023) · cites this paper as [4]
Drug intervention can slow down the aging phenotype to alleviate age-related functional decline.
“Recently, it has been proven that drug intervention can slow down the aging phenotype to alleviate age-related functional decline [176].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [176]
Several mTOR-targeting drugs, including rapalogs, have been developed to perturb cancer cell metabolism and are also explored as geroprotective strategies.
“Several mTOR-targeting drugs, including different rapalogs, have been developed to perturb cancer cell metabolism but are also being explored as part of geroprotective strategies.224,226”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [226]
Metformin, rapamycin, and dasatinib plus quercetin have shown benefit in non-clinical models of aging and AD.
“Three senolytics in current AD trials are metformin, rapamycin, and dasatinib plus quercetin; these therapies have shown benefit in non‐clinical models of aging and AD. 39 , 40 , 41”
From Alzheimer’s disease drug development pipeline: 2021 (2021) · cites this paper as [41]
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Hallmarks of aging: An expanding universe
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- Authors
- Partridge, L., Fuentealba, M., & Kennedy, B. K.
- Affiliations
- Max Planck Institute for Biology of Ageing (DE)
- Agency for Science, Technology and Research (SG)
- Corresponding author
- Partridge, Linda
- Kennedy, Brian K.
- Venue
- Nature Reviews Drug Discovery
- Published
- 2020-05-28
- Volume
- 19
- Issue
- 8
- Pages
- 513-532
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W3029220716
- Cited by
- 468
- References
- 395
- Citations by year
- 2026: 46 · 2025: 76 · 2024: 93 · 2023: 80 · 2022: 90 · 2021: 62 · 2020: 21
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (098565/Z/12/Z)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- aging, anti-aging interventions, healthspan, rapamycin, senolytics, metformin, acarbose, spermidine, lithium, nutrient sensing, cellular senescence, gut microbiota, age-related diseases, clinical trials, drug discovery
- MeSH terms
- Aging, Animals, Humans, Drug Discovery
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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