Genetic and epigenetic regulation of human aging and longevity
Open accessAbstract
Here we summarize the latest data on genetic and epigenetic contributions to human aging and longevity. Whereas environmental and lifestyle factors are important at younger ages, the contribution of genetics appears more important in reaching extreme old age. Genome-wide studies have implicated ~57 gene loci in lifespan. Epigenomic changes during aging profoundly affect cellular function and stress resistance. Dysregulation of transcriptional and chromatin networks is likely a crucial component of aging. Large-scale bioinformatic analyses have revealed involvement of numerous interaction networks. As the young well-differentiated cell replicates into eventual senescence there is drift in the highly regulated chromatin marks towards an entropic middle-ground between repressed and active, such that genes that were previously inactive "leak". There is a breakdown in chromatin connectivity such that topologically associated domains and their insulators weaken, and well-defined blocks of constitutive heterochromatin give way to generalized, senescence-associated heterochromatin, foci. Together, these phenomena contribute to aging.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Forests, parks, coastal areas, and mountainous regions are consistently associated with lower stress levels, improved cardiovascular function, and enhanced immune responses.
“Forests, parks, coastal areas, and mountainous regions, have been consistently associated with lower stress levels, improved cardiovascular function, and enhanced immune responses.”
From The Power of Environment: A Comprehensive Review of the Exposome's Role in Healthy Aging, Longevity, and Preventive Medicine-Lessons from Blue Zones and Cilento (2025) · cites this paper as [27]
The ‘Gene neighborhoods in longevity’ section discusses cellular stress responses involving FOXO3, not stress levels in people visiting natural settings. Searches for forests, parks, coastal and mountainous areas, and for natural-environment exposure found no passage linking those settings to cardiovascular function or immune responses in our copy. Page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 380 · Cited by 140
Research works printed but not linked: 1
- [93]Broer L, Buchman AS, Deelen J, Evans DS, Faul JD, Lunetta KL, Sebastiani P, Smith JA, Smith AV, Tanaka T, Yu L, Arnold AM, Aspelund T, Benjamin EJ, De Jager PL, Eirkisdottir G, Evans DA, Garcia ME, Hofman A, Kaplan RC, Kardia SL, Kiel DP, Oostra BA, Orwoll ES, Parimi N, Psaty BM, Rivadeneira F, Rotter JI, Seshadri S, Singleton A, Tiemeier H, Uitterlinden AG, Zhao W, Bandinelli S, Bennett DA, Ferrucci L, Gudnason V, Harris TB, Karasik D, Launer LJ, Peris TT, Slagboom PE, Tranah GJ, Weir DR, Newman AB, van Duijn CM, Murabito JM, GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy, J. Gerontol. A Biol. Sci. Med. Sci 70 (2015) 110– 118. 25199915 PMC4296168
- Authors
- Morris, B. J., Willcox, B. J., & Donlon, T. A.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- Corresponding author
- Morris, Brian J.
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2019-07
- Volume
- 1865
- Issue
- 7
- Pages
- 1718-1744
- ISSN
- 0925-4439 (ISSN-L)
- PMC
- PMC7295568
- OpenAlex
- W2889489983
- Cited by
- 140
- References
- 380
- Citations by year
- 2026: 7 · 2025: 23 · 2024: 23 · 2023: 17 · 2022: 24 · 2021: 26 · 2020: 10 · 2019: 7 · 2018: 1 · 2017: 1 · 2016: 1
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- National Institute on Aging
- Hawaii Community Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- human aging, longevity, lifespan, epigenetic regulation, chromatin regulation, cellular senescence, topologically associating domains, insulators, heterochromatin, senescence-associated heterochromatin foci, gene expression regulation, transcriptional regulatory networks, genetic loci, stress tolerance
- MeSH terms
- Aging, Chromatin, Histones, Humans, Longevity, Transcriptional Activation, Epigenesis, Genetic, Gene Regulatory Networks, Epigenomics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
