Humans could live significantly longer than currently thought if science focuses on defeating specific age-related pathologies, even without slowing the underlying biological process of ageing.
A review published in Genomic Psychiatry argues that tackling specific “bottlenecks to survival” — such as cardiovascular disease — can dramatically extend lifespan “well beyond current limits”.
Researchers from the German Center for Neurodegenerative Diseases (DZNE) challenge the fundamental metrics of the longevity field, identifying a “lifespan paradox” where interventions effectively extend life by removing specific threats without necessarily altering the rate at which the body ages.
“This pattern illustrates that interventions targeting specific pathologies can extend lifespan by addressing critical bottlenecks to survival, but they do not necessarily slow the overall ageing process,” write authors Dr Dan Ehninger and Dr Maryam Keshavarz.
The review presents a detailed cross-species analysis revealing that the causes of death vary wildly between organisms, suggesting that ageing manifests as a mosaic of specific mechanisms rather than a single universal decline.
Pure old age
In humans, cardiovascular disease accounts for 35 to 70 per cent of deaths among older adults, while autopsy studies show that even centenarians universally die from identifiable diseases rather than “pure old age”.
In contrast, neoplasia (cancer) dominates in mice, accounting for 84 to 89 per cent of age-related deaths across multiple studies. Consequently, an intervention that delays cancer in a mouse might significantly extend its life, without relevance to human cardiovascular ageing.
The authors draw parallels to the dramatic increase in human lifespan over the past two centuries. This shift was driven by vaccines and antibiotics conquering infectious diseases, a transition that delayed death without modifying the underlying biological rate of ageing.
The team conducted a provocative evaluation of the celebrated “hallmarks of ageing” framework, identifying a “striking methodological gap” in the evidence supporting it.
Upon analysing studies cited to support these hallmarks, the researchers found that between 56.86 and 99.96 per cent of supporting phenotypes were examined solely in aged animals, without parallel assessments in young treated cohorts.
When the researchers analysed the minority of studies that included young groups, they found that 436 out of 602 phenotypes — corresponding to 72.4 per cent — showed intervention effects in young animals as well as in old ones.
“Consequently, the evidence cited for most hallmarks supports the presence of general physiological effects rather than true antiaging mechanisms,” the review concludes.
Risk prediction
The authors also raised fundamental concerns about molecular tools such as epigenetic clocks, noting that while they are valuable for risk prediction, they often struggle to distinguish whether measured features causally influence ageing or merely reflect downstream consequences.
The review draws an illuminating analogy, noting that “estimating age based on facial images can be highly predictive, yet wrinkles and grey hair offer limited insight into the biological processes driving ageing”.
To resolve these ambiguities, the team proposes a new methodological framework that distinguishes between “rate effects” — in which treatments reduce the slope of age-dependent change — and “baseline effects”– in which treatments produce similar changes in both young and old subjects.
“Refining both discovery pipelines and intervention testing frameworks will support a more mechanistic understanding of ageing by enabling researchers to distinguish between interventions that simply extend lifespan or improve isolated age-sensitive phenotypes, and those that fundamentally modify the biological processes driving age-related decline,” the authors wrote.
