Longer life is not always slower aging, researchers warn

A lot of science headlines talk about slowing aging, reversing aging, or turning back the clock. It sounds simple: live longer, look younger, stay sharp, and call it victory.

But what if many of the tools used to claim “anti-aging” effects do not actually track aging itself, just shifts in sickness and symptoms?

A new scientific review argues that this is exactly the problem. The study takes a hard look at how experts measure aging in the lab and in people.

According to the researchers, quite a few popular methods may be giving a false sense of progress.

Asking the uncomfortable questions

The review comes from two researchers who spend their careers studying aging biology. Dr. Dan Ehninger, who leads the Translational Biogerontology Laboratory at the German Center for Neurodegenerative Diseases, and Dr. Maryam Keshavarz pulled together data from many animal and human studies.

The team addressed a simple but sharp question: when we say an intervention “slows aging,” what do we actually mean?

The researchers argue that common stand-ins for aging – including lifespan extension, epigenetic clocks, frailty scores, and even the famous hallmarks of aging – often blur two distinct ideas.

One is altering the pace at which aging unfolds over time; the other is shifting the body’s overall state in ways that don’t depend on age at all.

Living longer doesn’t mean aging slower

One part of the review looks at what actually kills organisms at older ages. In humans, cardiovascular disease consistently accounts for 35 to 70 percent of deaths among older adults.

Autopsy work shows that even centenarians who seemed healthy still died from clear diseases rather than from pure old age.

In one striking study of individuals aged 97 to 106 years, vascular conditions remained leading causes of mortality, which shows that even extreme longevity usually ends with specific pathologies.

Aging in other species

The picture is not the same in other species. In mice, neoplasia accounts for 84 to 89 percent of age-related deaths across multiple studies. In dogs, almost half of older animals die from cancer.

In captive nonhuman primates such as rhesus macaques, cardiovascular disease causes over 60 percent of deaths in aged animals.

Among invertebrates, intestinal or neuromuscular failure limits lifespan in Drosophila, while pharyngeal infections and deterioration drive mortality in C. elegans.

“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 aging process,” wrote the researchers.

Lessons from longer lives

Human life expectancy has shot up over the last two centuries. In the past, infectious diseases such as bubonic plague, smallpox, and tuberculosis were the main killers.

Vaccines, antibiotics, and sanitation cut deaths from these infections and moved the big health threats into later life.

The review points out that this historical shift mostly changed what people die from and when, rather than showing that human biology started aging more slowly.

In other words, if you remove one major cause of death, people live longer, but the deep cellular processes of aging can continue at the same pace.

That means a longer lifespan alone does not prove that an intervention targets the mechanisms that drive aging.

Aging clocks may only tell time

Epigenetic aging clocks, especially those built from DNA methylation patterns, have become popular for estimating biological age and testing “rejuvenation” strategies.

These clocks learn patterns that correlate strongly with chronological age and with risks of disease, so they look appealing for both research and commercial tests.

Dr. Ehninger and Dr. Keshavarz caution that these clocks are mostly correlational. They are trained on features that change with age, but those features might not cause aging. They may just be downstream effects or side notes.

The review highlights epigenome-wide Mendelian randomization studies that found traditional aging clocks are not significantly enriched for CpG sites with causal roles in aging, which raises doubts about treating clock changes as proof of slowed aging.

Many clocks also give only a snapshot in time, which makes it hard to tell whether a “younger” clock reading reflects a slower rate of aging or just a shifted baseline in certain biomarkers.

Frailty scores miss the bigger picture

Frailty indices in animals are often built from a small set of traits such as fur quality, spine curvature, or tumor presence, scored on simple scales and added together.

These are useful for some purposes, but they capture only a slice of all the ways bodies change with age.

The review notes that when all the traits in a frailty index are treated as equal, a change in one component, like a drop in tumor burden, can lower the total score and make an intervention look like it broadly affects aging.

In reality, the effect may sit mostly in one pathology and say little about the trajectory of the wider organism.

The hallmarks of aging

The hallmarks of aging framework, first proposed in 2013 and expanded to 12 hallmarks in 2023, has guided much of modern aging research.

The framework lists features such as genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, and cellular senescence as core drivers of aging and suggests that targeting them should change how aging unfolds.

To see whether the evidence really supports that claim, Dr. Keshavarz and Dr. Ehninger went back to the primary papers cited for each hallmark, focusing on studies used to argue for causal links.

Limitations of past studies

The experts report that between 56.86 and 99.96 percent of supporting phenotypes for each hallmark were tested only in aged animals, without matching experiments in young treated animals.

Without those young groups, it is extremely hard to tell whether a change reflects a slower rate of age-related decline or a general effect that is similar at all ages.

In the subset of 602 phenotypes that did include young animals, 436, corresponding to 72.4 percent, showed intervention effects in young groups as well.

“Consequently, the evidence cited for most hallmarks supports the presence of general physiological effects rather than true anti-aging mechanisms,” the experts concluded.

Open questions about how bodies age

The review highlights several unanswered questions. Tissues do not age at identical speeds, and the reasons are murky.

Differences in development, cell turnover, metabolic demand, and exposure to stress all likely play a role, yet the exact mix is not settled.

The authors also note that species die from very different primary causes: cardiovascular disease in humans, neoplasia in mice, infections in fish, intestinal or neuromuscular failure in flies, bacterial infection in worms.

That pattern suggests aging is a patchwork of species- and tissue-specific mechanisms shaped by evolution and environment, rather than a single universal program.

The full study was published in the journal Genomic Psychiatry.

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