# Methylation and algorithms in biological aging: a scoping review

**Authors:** Alison Ziesel, Jennifer Reeves, Anastasia Mallidou, Lorelei Newton, Ryan E. Rhodes, Jie Zhang, Theone Paterson, Hosna Jabbari

PMC · DOI: 10.3389/fragi.2025.1682873 · Frontiers in Aging · 2025-12-18

## TL;DR

This paper reviews how DNA methylation and algorithms are used to study biological aging and measure age differences.

## Contribution

The paper provides a scoping review of methylation-based strategies and algorithmic methods for biological age assessment.

## Key findings

- Methylation-based strategies have evolved over time to better measure biological age.
- Novel methylation clocks and algorithms have been developed for age assessment.
- The review highlights both consistent and conflicting research findings in the field.

## Abstract

The role of DNA methylation in the process of biological aging is a particularly active area of research, where methylation changes may be a consequence or a driver in the deviation between biological and chronological age. We employ a scoping review strategy to analyze the results of 435 relevant research papers, 167 of which employed methylation-based strategies to interrogate biological age. Our work details the progression and refinement of these strategies over time, as well as the development of novel methylation-based clocks and algorithmic methods. Our chosen review strategy allows for the identification of research findings consistent and discordant with one another, as well as focusing on exciting, potential research areas regarding measurement, calculation, and assessment of epigenetic biological age.

## Full-text entities

- **Genes:** PCDHGA3 (protocadherin gamma subfamily A, 3) [NCBI Gene 56112] {aka PCDH-GAMMA-A3}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, EDARADD (EDAR associated via death domain) [NCBI Gene 128178] {aka CR, ECTD11A, ECTD11B, ED3, EDA3}, ELOVL2 (ELOVL fatty acid elongase 2) [NCBI Gene 54898] {aka SSC2}, PDE4C (phosphodiesterase 4C) [NCBI Gene 5143] {aka DPDE1, PDE21}, ISYNA1 (inositol-3-phosphate synthase 1) [NCBI Gene 51477] {aka INO1, INOS, IPS, IPS 1, IPS-1}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, RAB32 (RAB32, member RAS oncogene family) [NCBI Gene 10981] {aka PARK26}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, RHOT2 (ras homolog family member T2) [NCBI Gene 89941] {aka ARHT2, C16orf39, MIRO-2, MIRO2, RASL}, LRRK2 (leucine rich repeat kinase 2) [NCBI Gene 120892] {aka AURA17, DARDARIN, PARK8, RIPK7, ROCO2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, NR3C1 (nuclear receptor subfamily 3 group C member 1) [NCBI Gene 2908] {aka GCCR, GCR, GCRST, GR, GRL}, CRAT (carnitine O-acetyltransferase) [NCBI Gene 1384] {aka CAT, CAT1, NBIA8}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, ITGA2B (integrin subunit alpha 2b) [NCBI Gene 3674] {aka BDPLT16, BDPLT2, CD41, CD41B, FMAIT2, GP2B}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, ASPA (aspartoacylase) [NCBI Gene 443] {aka ACY2, ASP}
- **Diseases:** fibrosis (MESH:D005355), ALS (MESH:D000690), hyperglycemia (MESH:D006943), trauma (MESH:D014947), inflammatory (MESH:D007249), Parkinson's (MESH:D010300), apnea (MESH:D001049), hyperglycemic (MESH:D006944), Hypertension (MESH:D006973), daytime sleepiness (MESH:D012893), pain (MESH:D010146), life (MESH:D003643), diabetic complications (MESH:D048909), psychosocial (MESH:C535569), Diabetes (MESH:D003920), atrial fibrillation (MESH:D001281), COVID19 (MESH:D000086382), Morbidity (OMIM:614963), diabetic retinopathy (MESH:D003930), psychotic (MESH:D011618), ADHD (MESH:D001289), ischemic stroke (MESH:D002544), cancer (MESH:D009369), infertility (MESH:D007246), MCI (MESH:D060825), myocardial infarction (MESH:D009203), impairment of activities of (MESH:D001523), abuse (MESH:D019966), cardiovascular disease (MESH:D002318), age-related disease (MESH:D010024), HRS (OMIM:603663), schizophrenia (MESH:D012559), NAS (MESH:D019588), Anxiety (MESH:D001007), pre-eclampsia (MESH:D011225), head and neck cancer (MESH:D006258), Autism (MESH:D001321), Weight loss (MESH:D015431), gestational diabetes (MESH:D016640), Depression (MESH:D003866), Non-alcoholic steatohepatitis (MESH:D005235), Breast tumor (MESH:D001943), obese (MESH:D009765), triple-negative (MESH:D064726), knee pain (MESH:D046788), obstructive coronary artery disease (MESH:D003324), type I diabetics (MESH:D003922), overweight (MESH:D050177), dementia (MESH:D003704), stroke (MESH:D020521), HANDLS (MESH:C562385), COPD (MESH:D029424), disordered breathing (MESH:D012891), PTSD (MESH:D013313), Metabolic dysregulation (MESH:D021081), Multiple sclerosis (MESH:D009103), Chronic disease (MESH:D002908), frailty (MESH:D000073496), Cognitive dysfunction (MESH:D003072), neuropathological (MESH:D009422)
- **Chemicals:** vitamin D (MESH:D014807), polybrominated biphenyl (MESH:D011075), metal (MESH:D008670), organochlorine pesticides (-), clozapine (MESH:D003024), zinc (MESH:D015032), sulfate (MESH:D013431), mercury (MESH:D008628), 25-hydroxyvitamin D (MESH:C104450), inorganic phosphate (MESH:D010710), nickel (MESH:D009532), ammonium (MESH:D064751), metformin (MESH:D008687), cobalt (MESH:D003035), vanadium (MESH:D014639), Alcohol (MESH:D000438), cadmium (MESH:D002104), arsenic (MESH:D001151), vitamin B6 (MESH:D025101), lead (MESH:D007854), barium (MESH:D001464), folate (MESH:D005492), glucose (MESH:D005947), manganese (MESH:D008345), nitric oxides (MESH:D009569), cholesterol (MESH:D002784)
- **Species:** Homo sapiens (human, species) [taxon 9606], Human immunodeficiency virus 1 (no rank) [taxon 11676], Nicotiana tabacum (American tobacco, species) [taxon 4097], Cytomegalovirus (genus) [taxon 10358]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12756485/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12756485/full.md

## References

196 references — full list in the complete paper: https://tomesphere.com/paper/PMC12756485/full.md

---
Source: https://tomesphere.com/paper/PMC12756485