ReviewAgeing research reviews2022
The hyperfunction theory: An emerging paradigm for the biology of aging.
Review in Ageing research reviews, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
70 citing papers in PubMed.
- Weight Regain Reverses Caloric Restriction-Induced Benefits on the Insulin-IGF-1 Nutrient-Sensing Pathway: Post Hoc Analysis From the CALERIE-2 Randomized Controlled Trial.Diabetes care · 2026Trial
- A conserved post-maturity imbalance between housekeeping and integrative genome activity in aging.GeroScience · 2026Article
- Physiological Age and Homeostatic Dysregulation Following Child Maltreatment in Youth.Molecular psychiatry · 2026Article
- Review
- Embracing non-linearity in human ageing.Nature reviews. Genetics · 2026Review
- Reversing aging-like 3D genome disorganization in abioRxiv : the preprint server for biology · 2026Article
- Review
- Old worms, new tricks: dynamical instability explains late-life rejuvenation inbioRxiv : the preprint server for biology · 2026Article
- Gene expression and co-expression heterogeneity patterns and biodemography analyses during the cell cycle encourage aging studies in archaea.GeroScience · 2026Article
- In Vivo Chemical Reprogramming Is Associated With a Toxic Accumulation of Lipid Droplets Hindering Rejuvenation.Aging cell · 2026Article
- Epigenetic program of ontogenesis and hyperfunction theory: reinterpreting the mechanisms of aging.Frontiers in aging · 2026Article
- EWAS in a polyphenol dense, DNA methylation-targeted, controlled diet and lifestyle study.Frontiers in nutrition · 2026Article
- Integrating evolutionary theory into a framework for the mechanistic evaluation of candidate anti-aging interventions.Frontiers in aging · 2026Article
- Evolutionary perspectives on endometrial cancer: antagonistic pleiotropy.Molecular & cellular oncology · 2026Review
- Review
- Aging as a Loss of Goal-Directedness: An Evolutionary Simulation and Analysis Unifying Regeneration with Anatomical Rejuvenation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Astrocytes as Metabolic Sensors Orchestrating Energy-Driven Brain Vulnerability in Alzheimer's Disease.Journal of neurochemistry · 2025Review
- The Bioelectrics of Immortality and Mortality in Cold-SensitiveBioelectricity · 2025Article
- How aging causes osteoarthritis: An evolutionary physiology perspective.Osteoarthritis and cartilage · 2025Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
Abstract
The process of senescence (aging) is predominantly determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function that senescence serves, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood's disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is assessed.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.