In the VascularVita longevity programme, healthspan is the period in which a person can live independently and keep up daily tasks. Terms such as “biological age”, “epigenetic clock” and “ageing panel” are used often in this field. The evidence behind each of them is not of the same strength. The shared question for the clinical team and for the person being advised is: which evidence tier does this claim rest on, and which outcome does it measure?
This article summarises how to interpret evidence tiers in a healthspan setting. The nine hallmarks of ageing give the biological map. The name of a single hallmark is not enough to choose a test or a medicine. Functional stages are defined in healthspan, and the follow-up flow on the ageing stages page.
Why a tier is needed
In longevity, three kinds of source are often mixed together: basic science (cell and animal studies), early human studies, and established clinical guidelines. When all of them are called “evidence” in the same sentence, a clinical decision and a research observation look equally supported. A tier separates which data support which decision.
Regular exercise, for example, has been shown in many randomised controlled trials to affect walking capacity and frailty. By contrast, small studies reporting that an NAD⁺ precursor changes a blood marker do not show that healthspan has been extended. An epigenetic clock or telomere length is associated with risk at population level. That association is not enough for a treatment plan in one person.
H1–H4 in practice
In the VascularVita internal protocol, human evidence is coded at four levels. The code does not mean an intervention will be applied to everyone. It shows only how far the claim in question is supported by human data.
- H1, guidelines and many randomised trials: A functional or clinical outcome has been shown. Examples: stopping smoking, blood-pressure and lipid management, indicated antiplatelet treatment, supervised exercise programmes.
- H2, an early human study or an authorised treatment in a defined disease: Phase II studies, or treatments included in a guideline for a diagnosed disease. This does not show that healthspan is extended in the general population.
- H3, observational data and biomarkers: Cohort studies, small series, an epigenetic clock or inflammation markers. They generate a hypothesis; they do not set a treatment decision on their own.
- H4, preclinical data: Animal and cell studies, mechanism data. They set the direction of research; they are not used for a clinical decision.
Different interventions aimed at the same biological hallmark can belong to different tiers. In inflammation and vascular ageing, lipid and antiplatelet treatment in diagnosed vascular disease is H1. Interventions in a healthy person based on an inflammation panel remain at H3.
Relation to the classic evidence pyramid
The evidence pyramid of clinical epidemiology — systematic review and meta-analysis, randomised controlled trial, cohort, case series, expert opinion and mechanism — holds in the longevity discussion as well. What changes the interpretation is the choice of outcome. In healthspan the priority outcomes are walking, activities of daily living, cognitive function and independence. A laboratory value returning to the reference range is not, on its own, high-level evidence.
The World Health Organization ICOPE framework assesses intrinsic capacity in five domains: locomotion, cognition, vitality (nutrition), sensory function (vision and hearing) and psychological state. Validated clinical scales such as the Fried frailty phenotype are also used in frailty assessment. These tools measure function directly, so they are not replaced by molecular panels.
Where the tier draws a line
The evidence tier explains why some common practices are not enough for a clinical decision. Calculating a “biological age” from a single test and proposing a treatment package from it uses H3 data as if it were H1. Building an automatic medicine list from an ageing panel is the same error. Applying a result from animal studies straight to a patient carries H4 data into a clinical decision.
Vascular integrity and perfusion are one of the pillars of healthspan; that link is described in vascular health and longevity. The same question is asked of a new agent aimed at the vessel: is there randomised evidence on a functional outcome?
Order in clinical practice
- Functional screening: ICOPE domains, walking speed, grip strength, functional stages.
- Standard risk and diagnosis: Diabetes, peripheral artery disease, venous insufficiency, chronic wounds. Guideline-based treatment.
- Selected research: Biomarker measurement tied to a protocol. The result does not change the clinical decision on its own.
This order simplifies both the clinician–patient conversation and decisions inside an institutional committee. Marketing a product as a “longevity product” is no substitute for H1 evidence.
Summary
Claims about healthspan should be interpreted by evidence tier. At the top are interventions whose functional outcomes have been shown in randomised trials; at the bottom, mechanism and early biomarker data. The hallmarks of ageing offer a biological map; they are not, on their own, enough to choose a test or a medicine.
Sources
- López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186(2):243–278. doi:10.1016/j.cell.2022.11.001
- Martinović A, et al. Climbing the longevity pyramid: overview of evidence-driven healthcare prevention strategies for human longevity. Front Aging. 2024;5:1495029. doi:10.3389/fragi.2024.1495029
- Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146–M156. doi:10.1093/gerona/56.3.m146
- Cesari M, et al. Evidence for the domains supporting the construct of intrinsic capacity. J Gerontol A Biol Sci Med Sci. 2018;73(12):1653–1660. doi:10.1093/gerona/gly011
- World Health Organization. World report on ageing and health. Geneva: WHO; 2015. who.int