These are further passages of the nine texts this paper read, word for word, grouped by text. The government work is in the public domain; the eight articles are published under a Creative Commons Attribution licence. Findings are their authors', with the limits their authors state, and the paper's reading of them is its own interpretation.
Gems, The aging-disease false dichotomy (2015)
An essay by a biogerontologist arguing that ageing is best understood as pathology.
Is senescence a disease? The very word senescence, denoting deterioration leading to death, certainly carries that implication.
Life extending treatments in the laboratory invariably decelerate aging (rather than stopping or reversing it); this results in a delay in the appearance of age-related pathology (extending youthspan), but then such pathologies still eventually appear, causing illness, and death.
The question of how to define anti-aging (or geroprotective) treatments is an open one, and I have discussed it more fully elsewhere (Gems, 2014).
I suspect that the more utopian definition of geroprotection, though inspiring to biogerontologists, is a turn-off for clinicians, who view it as unrealistic.
Barzilai, Healthy life extension (2026)
A commentary by a physician on the goal of geroscience and the outcomes by which it should be judged.
The only mission that is both scientifically coherent and clinically meaningful is healthy life extension: more years in full health.
Blagosklonny’s insistence on lifespan evidence was field-building: a protest against a literature that celebrates “healthspan” using endpoints so elastic that they cannot fail.
The practical bridge is to demand the right kinds of rigor, namely replicable lifespan effects in mammals where feasible, paired with human endpoints that map to health-adjusted survival, including delayed multimorbidity, frailty, function, and immune resilience.
Frailty and function are not soft outcomes.
Scott and others, The economic value of targeting aging (2021)
An article in economics, calibrated to United States data, comparing four imagined ways of changing how people age.
What are the gains from targeting aging itself compared to efforts to eradicate specific diseases?
We show that a slowdown in aging that increases life expectancy by 1 year is worth US$38 trillion, and by 10 years, US$367 trillion.
Although our dollar WTP values are sensitive to the precise calibration of our model, the relative importance of different treatments for aging is not.
Our estimates abstract from both inequalities in health and income.
In other words, measurement of aging biologically rather than chronologically leads to increasing returns for aging at the individual level, feeding into even greater increasing returns at the aggregate level.
Horvath, DNA methylation age of human tissues and cell types (2013)
The article that introduced a predictor of age from DNA methylation across most tissues and cell types.
It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure.
I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system.
It remains to be seen whether the DNAm age of easily accessible fluids/tissues (for example, saliva, buccal cells, blood, skin) can serve as a surrogate marker for inaccessible tissues (for example, brain, kidney, liver).
Future research will need to clarify whether DNAm age is only a marker of aging or relates to an effector of aging.
Belsky and others, Pace of biological aging (2020)
The article that built a blood test for the pace of ageing from a birth cohort followed over twelve years.
A useful measure should be non-invasive, inexpensive, reliable, and highly sensitive to biological change.
As a result, the clocks confound methylation patterns arising from early-life exposures to methylation-altering factors with methylation patterns related to biological aging during adulthood.
Ultimately, data on DunedinPoAm for all CALERIE participants (and participants in other geroprotector trails) at trial baseline and follow-up will be needed to establish utility of DunedinPoAm as a surrogate endpoint.
Foremost, DunedinPoAm is a first step toward a single-assay cross-sectional measurement of Pace of Aging.
Follow-up of DunedinPoAm in more diverse samples is needed to establish cross-population validity.
Fahy and others, Reversal of epigenetic aging (2019)
A report of a small pilot trial in healthy men, read here for how it uses epigenetic clocks as evidence.
Epigenetic “clocks” can now surpass chronological age in accuracy for estimating biological age.
The present study strongly supports this approach, having demonstrated regression of epigenetic age with high statistical significance even in a one‐year pilot trial involving only 9 volunteers.
It remains to be seen whether follow‐up measurements of epigenetic aging using the GrimAge clock will show a persistent 2‐year gain in predicted life expectancy or a gradual loss of increased life expectancy compared to baseline.
Although much more remains to be done, the general prospects for meaningful amelioration of human aging appear to be remarkably promising.
Mattison and others, Caloric restriction in rhesus monkeys (2017)
A comparison of two long-running studies in monkeys that had reported different effects on survival.
Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial.
The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect.
The initial goal of both NIA and UW studies was to determine the impact of CR on the health of rhesus monkeys, as it was not a foregone conclusion that CR would be an appropriate intervention in long-lived species.
The rationale for these design features at UW was to implement a study as it might have been conducted in humans.
Although the numerical values for estimated survival were lower in CR groups than in controls, the impact of juvenile onset CR on survival remains undetermined, as the mortality curves for both NIA J/A cohorts are incomplete.
Waziry and others, CALERIE DNA methylation analysis (2023)
A post hoc analysis of DNA methylation measures of ageing in a randomized trial of caloric restriction in adults.
The finding that CR modified DunedinPACE in a randomized controlled trial supports the geroscience hypothesis, building on evidence from small and uncontrolled studies
Ultimately, a conclusive test of the geroscience hypothesis will require trials with long-term follow-up to establish effects of intervention on primary healthy-aging endpoints, including incidence of chronic disease and mortality
However, these DNAm measures were developed using different methods and reflect different models of aging.
The CALERIE Trial sample does not represent the general population and treatment effects may not generalize beyond the population of healthy volunteers recruited to participate.
Whether treatment and any slowing in biological aging that resulted from it translated to long-term clinical benefit is currently unknown.
ARPA-H, PROSPR programme page
The programme page of a United States federal research programme on healthspan, a public-domain government work.
What if we had therapies to extend healthspan and prevent the onset of age-related diseases?
In response to these issues, the PROactive Solutions for Prolonging Resilience (PROSPR) program aims to identify biochemical and physiological markers and develop assessment tools that will allow researchers to better understand and target the underlying causes of age-related disease.
If successful, PROSPR will build a new therapeutic industry with interventions focused on maintaining health during aging.
A revolutionary approach to extending the healthspan of people across the U.S. requires a comfort with calculated research that only a funding agency such as ARPA-H can provide.