# Molecular pathways linking chronic psychological stress to accelerated aging: mechanisms and interventions

**Authors:** Othman A. Alhazzaa, Hanin M. Abahussin, Majed A. Majrashi, Maryam S. Alotaibi, Mohammad N. Alkhrayef, Ziyad A. Alhamdan, Abdullah O. Alawad

PMC · DOI: 10.3389/fragi.2026.1743142 · Frontiers in Aging · 2026-02-04

## TL;DR

This paper explores how chronic psychological stress speeds up aging and suggests ways to counteract its harmful effects.

## Contribution

The paper reviews recent mechanisms linking chronic stress to aging and proposes interventions to mitigate these effects.

## Key findings

- Chronic psychological stress is linked to aging hallmarks like mitochondrial dysfunction and telomere attrition.
- Intervention strategies may help reduce the adverse effects of chronic stress on aging.
- Current research gaps highlight the need for further study on stress-aging interactions.

## Abstract

Chronic psychological stress refers to repeated or prolonged exposure to adverse social or emotional threats that exceed an individual’s adaptive capacity. It is recognized as a risk factor for aging-associated diseases. A growing body of research has shown that there is a link between chronic psychological stress and accelerated aging. Here, we highlight recent findings on the interconnected relationship between chronic psychological stress and major aging hallmarks, including mitochondrial dysfunction, telomere attrition, cellular senescence, epigenetic alterations, inflammation, and genomic instability. We discuss the mechanisms by which chronic psychological stress may drive this effect and explore intervention strategies that could mitigate its adverse effects and promote healthy aging. Moreover, we address current research gaps and propose future research directions to improve our understanding of the intricate relationship between psychological stress and aging.

## Full-text entities

- **Genes:** PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, RB1 (RB transcriptional corepressor 1) [NCBI Gene 5925] {aka OSRC, PPP1R130, RB, p105-Rb, p110-RB1, pRb}, ATM (ATM serine/threonine kinase) [NCBI Gene 472] {aka AT1, ATA, ATC, ATD, ATDC, ATE}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, NOX4 (NADPH oxidase 4) [NCBI Gene 50507] {aka KOX, KOX-1, RENOX}, RAD51 (RAD51 recombinase) [NCBI Gene 5888] {aka BRCC5, FANCR, HRAD51, HsRad51, HsT16930, MRMV2}, PINK1 (PTEN induced kinase 1) [NCBI Gene 65018] {aka BRPK, PARK6}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, CD38 (CD38 molecule) [NCBI Gene 952] {aka ADPRC 1, ADPRC1, cADPR1}, CRH (corticotropin releasing hormone) [NCBI Gene 1392] {aka CRF, CRH1}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, Cdkn2a (cyclin dependent kinase inhibitor 2A) [NCBI Gene 12578] {aka ARF-INK4a, Arf, INK4a-ARF, Ink4a/Arf, MTS1, Pctr1}, OGG1 (8-oxoguanine DNA glycosylase) [NCBI Gene 4968] {aka HMMH, HOGG1, MUTM, OGH1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, NR3C1 (nuclear receptor subfamily 3 group C member 1) [NCBI Gene 2908] {aka GCCR, GCR, GCRST, GR, GRL}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Snca (synuclein, alpha) [NCBI Gene 20617] {aka NACP, alpha-Syn, alphaSYN}, SOD2 (superoxide dismutase 2) [NCBI Gene 6648] {aka GC1, GClnc1, IPO-B, IPOB, MNSOD, MVCD6}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Nr4a1 (nuclear receptor subfamily 4, group A, member 1) [NCBI Gene 15370] {aka GFRP1, Gfrp, Hbr-1, Hbr1, Hmr, N10}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, XRCC1 (X-ray repair cross complementing 1) [NCBI Gene 7515] {aka RCC, SCAR26}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, CGAS (cyclic GMP-AMP synthase) [NCBI Gene 115004] {aka C6orf150, D4, MB21D1, h-cGAS}, CAT (catalase) [NCBI Gene 847], APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1) [NCBI Gene 328] {aka APE, APE1, APEN, APEX, APX, HAP1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Ucp2 (uncoupling protein 2 (mitochondrial, proton carrier)) [NCBI Gene 22228] {aka Slc25a8, UCP 2, UCPH}, Pink1 (PTEN induced putative kinase 1) [NCBI Gene 68943] {aka 1190006F07Rik, BRPK, mFLJ00387}, FKBP5 (FKBP prolyl isomerase 5) [NCBI Gene 2289] {aka AIG6, FKBP51, FKBP54, P54, PPIase, Ptg-10}, Slc25a14 (solute carrier family 25 (mitochondrial carrier, brain), member 14) [NCBI Gene 20523] {aka BMCP1, UCP5, UCP5L, UCP5S}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, SIRT3 (sirtuin 3) [NCBI Gene 23410] {aka SIR2L3}, CHGA (chromogranin A) [NCBI Gene 1113] {aka CGA, PHE5, PHES}, Cdkn1a (cyclin dependent kinase inhibitor 1A) [NCBI Gene 12575] {aka CAP20, CDKI, CIP1, Cdkn1, P21, SDI1}, BRCA1 (BRCA1 DNA repair associated) [NCBI Gene 672] {aka BRCAI, BRCC1, BROVCA1, FANCS, IRIS, PNCA4}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, Slc25a27 (solute carrier family 25, member 27) [NCBI Gene 74011] {aka 3632410G24Rik, 9430092A03Rik, D530043E16Rik, UCP 4, Ucp4}, POMC (proopiomelanocortin) [NCBI Gene 5443] {aka ACTH, CLIP, LPH, MSH, NPP, OBAIRH}, CDKN1B (cyclin dependent kinase inhibitor 1B) [NCBI Gene 1027] {aka CDKN4, KIP1, MEN1B, MEN4, P27KIP1}
- **Diseases:** PD (MESH:D010300), Mitochondrial dysfunction (MESH:D028361), emotional disturbances (MESH:D014832), anhedonia (MESH:D059445), Sleep (MESH:D012893), dyslipidemia (MESH:D050171), glucocorticoid resistance (MESH:C564221), Neurodegenerative (MESH:D019636), trauma (MESH:D014947), Chronic Inflammation (MESH:D007249), neuronal atrophy (MESH:D001284), anxiety (MESH:D001007), neuroinflammation (MESH:D000090862), diabetes (MESH:D003920), cancer (MESH:D009369), mental disorders (MESH:D001523), AD (MESH:D000544), neglect (MESH:D058069), fatigue (MESH:D005221), autoimmune disease (MESH:D001327), stress-related disorders (MESH:D000068099), low mood symptoms (MESH:D019964), frailty (MESH:D000073496), synaptic loss (MESH:D012183), depressive and anxiety disorders (MESH:D001008), psychological distress (MESH:D012128), metabolic dysregulation (MESH:D021081), major depression (MESH:D003865), OA (MESH:D010003), metabolic (MESH:D008659), stiffness (MESH:C566112), impaired emotional regulation (MESH:C565631), age-related diseases (MESH:D010024), insulin resistance (MESH:D007333), age- (MESH:D019588), mental health disorder (OMIM:603663), sexual abuse (MESH:D000082002), weight loss (MESH:D015431), psychological disorders (MESH:D000067073), deficits in executive functioning (MESH:D001289), cardiovascular complications (MESH:D002318), infection (MESH:D007239), dementia (MESH:D003704), telomere dysfunction (MESH:C536801), rotator cuff tendinopathy (MESH:D000070636), mucositis (MESH:D052016), depression (MESH:D003866), type 2 diabetes (MESH:D003924), sleep deprivation (MESH:D012892), inflammatory cytokines (MESH:D000080424), neuronal degeneration (MESH:D009410), chronic disease (MESH:D002908), cognitive and functional decline (MESH:D003072), synaptic dysfunction (MESH:C536122)
- **Chemicals:** oxygen (MESH:D010100), Rapamycin (MESH:D020123), adrenaline (MESH:D004837), corticosterone (MESH:D003345), Cortisol (MESH:D006854), PGE2 (MESH:D015232), CL (MESH:D002308), Metformin (MESH:D008687), EPA (MESH:D015118), buspirone (MESH:D002065), PGD2 (MESH:D015230), 8-oxo-2'-deoxyguanosine (MESH:D000080242), kynurenine (MESH:D007737), noradrenaline (MESH:D009638), isoprostane (MESH:D028421), Resveratrol (MESH:D000077185), caffeine (MESH:D002110), polyunsaturated fatty acids (MESH:D005231), benzodiazepines (MESH:D001569), phosphatidylethanolamine (MESH:C483858), SAM (-), superoxide (MESH:D013481), olive oil (MESH:D000069463), NMN (MESH:D009537), RNS (MESH:D026361), catecholamine (MESH:D002395), dexamethasone (MESH:D003907), nucleosides (MESH:D009705), DHA (MESH:D004281), lipid (MESH:D008055), oxylipins (MESH:D054883), polyphenol (MESH:D059808), ATP (MESH:D000255), ROS (MESH:D017382), NR (MESH:C018613), glucose (MESH:D005947), simvastatin (MESH:D019821), alcohol (MESH:D000438), NAD+ (MESH:D009243)
- **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mus musculus (house mouse, species) [taxon 10090], Arachis hypogaea (goober, species) [taxon 3818], Homo sapiens (human, species) [taxon 9606], Rodentia (rodent, order) [taxon 9989], Rattus norvegicus (brown rat, species) [taxon 10116]

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## References

313 references — full list in the complete paper: https://tomesphere.com/paper/PMC12914971/full.md

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Source: https://tomesphere.com/paper/PMC12914971