Endocrine Regulation in Aging: Hormonal Decline, Compensatory Mechanisms, and Prospects for Healthy Aging Interventions
DOI:
https://doi.org/10.64229/x6gbxf06Keywords:
Aging endocrine, Hormonal control, Metabolic impairment, Geroscience intervention, Precision endocrinologyAbstract
This study examines the processes, physiological outcomes, and novel interventions of endocrine aging through a systematic evidence-based analysis methodology. Peer-reviewed research published between 2020 and 2025 provided data collected on the basis of competitive endocrine achievements, hormonal disorderliness, and multi-organizational biological outcomes analyzed using predetermined inclusion criteria. The research also examines the modern and developing treatment methods, such as hormone modulation, lifestyle change, pharmacological agents, and precision endocrinology. The study suggest that endocrine aging is a consequence of progressive dysfunction in the production of hormones, the sensitivity of receptors, and cross-axis feedback regulation, which causes metabolic dysfunction, immune dysfunction, neurocognitive dysfunction, and frailty. New hormonal-based interventions show promise to enhance endocrine resistance and healthy lifespan. The paper identifies some major gaps in research in the areas of biomarker development, integration of multi-omics, artificial intelligence, and ethical aspects of hormone-based longevity treatment.
References
[1]Cappola AR, Auchus RJ, Fuleihan GE, Handelsman DJ, Kalyani RR, McClung MR, et al. Hormones and aging: An endocrine society scientific statement. The Journal of Clinical Endocrinology and Metabolism, 2023, 108(8), 1835-1874. DOI: 10.1210/clinem/dgad225
[2]van den Beld AW, Kaufman JM, Zillikens MC, Lamberts SW, Egan JM, van der Lely AJ. The physiology of endocrine systems with ageing. The Lancet Diabetes & Endocrinology, 2018, 6(8), 647-658. DOI: 10.1016/S2213-8587(18)30026-3
[3]Sellegounder D, Ferrucci L, Anbazhagan R, Basisty N. Molecular crosstalk between endocrine factors, paracrine signals, and the immune system during aging. Frontiers in Endocrinology, 2023, 14, 1203755. DOI: 10.3389/fendo.2023.1203755
[4]Harper J. Editorial: Insights in endocrinology of aging: 2021. Frontiers in Endocrinology, 2022, 13, 1066216. DOI: 10.3389/fendo.2022.1066216
[5]Camon C, Garratt M, Correa SM. Exploring the effects of estrogen deficiency and aging on organismal homeostasis during menopause. Nature Aging, 2024, 4(12), 1731-1744. DOI: 10.1038/s43587-024-00767-0
[6]Ezkurdia A, Ramírez MJ, Solas M. Metabolic syndrome as a risk factor for Alzheimer’s disease: A focus on insulin resistance. International Journal of Molecular Sciences, 2023, 24(5), 4354. DOI: 10.3390/ijms24054354
[7]Wang SL, Shi YQ, Xin R, Kang HL, Xiong HZ, Ren JX. Exploring the role of insulin resistance in bridging the metabolic syndrome and Alzheimer’s disease-a review of mechanistic studies. Frontiers in Endocrinology, 2025, 16, 1614006. DOI: 10.3389/fendo.2025.1614006
[8]Li MH, Ji R, Liu X, Wu YJ. Associations of metabolic syndrome and its components with sarcopenia, and the mediating role of insulin resistance: Findings from NHANES database. BMC Endocrine Disorders, 2024, 24(1), 203. DOI: 10.1186/s12902-024-01736-9
[9]Khalaf F, Barayan D, Saldanha S, Jeschke MG. Metabolaging: A new geroscience perspective linking aging pathologies and metabolic dysfunction. Metabolism, 2025, 166, 156158. DOI: 10.1016/j.metabol.2025.156158
[10]Cheng HY, Zhang XY, Li YH, Cao DZ, Luo CL, Zhang Q, et al. Age-related testosterone decline: Mechanisms and intervention strategies. Reproductive Biology and Endocrinology, 2024, 22(1), 144. DOI: 10.1186/s12958-024-01316-5
[11]Tsutsumi T, Tsuchiya K. Testosterone and obesity in an aging society. Biomolecules, 2025, 15(11), 1521. DOI: 10.3390/biom15111521
[12]Cao X, Thyfault JP. Exercise drives metabolic integration between muscle, adipose and liver metabolism and protects against aging-related diseases. Experimental Gerontology, 2023, 176, 112178. DOI: 10.1016/j.exger.2023.112178
[13]Basisty N, Kale A, Jeon OH, Kuehnemann C, Payne T, Rao C, et al. A proteomic atlas of senescence-associated secretomes for aging biomarker development. PLoS Biology, 2020, 18(1), e3000599. DOI: 10.1371/journal.pbio.3000599
[14]Xing YT, Xuan F, Wang KX, Zhang HF. Aging under endocrine hormone regulation. Frontiers in Endocrinology, 2023, 14, 1223529. DOI:10.3389/fendo.2023.1223529
[15]Wei R, Du ZH, Wang J, Bi JL, Lyu W, Wang HC, et al. A single-cell transcriptomic landscape characterizes the endocrine system aging in the mouse. Protein & Cell, 2025, 17(1), 27-45. DOI: 10.1093/procel/pwaf074
[16]Kolb H, Kempf K, Martin S. Insulin and aging - a disappointing relationship. Frontiers in endocrinology, 2023, 14, 1261298. DOI: 10.3389/fendo.2023.1261298
[17]Mahboobifard F, Pourgholami MH, Jorjani M, Dargahi L, Amiri M, Sadeghi S, et al. Estrogen as a key regulator of energy homeostasis and metabolic health. Biomedicine & Pharmacotherapy, 2022, 156, 113808. DOI: 10.1016/j.biopha.2022.113808
[18]Mantovani A, Garlanda C. Humoral innate immunity and acute-phase proteins. The New England Journal of Medicine, 2023, 388(5), 439-452. DOI: 10.1056/nejmra2206346
[19]Pöllänen PM, Härkönen T, Ilonen J, Toppari J, Veijola R, Siljander H, et al. Autoantibodies to N-terminally truncated GAD65 (96-585): HLA associations and predictive value for type 1 diabetes. The Journal of Clinical Endocrinology & Metabolism, 2022, 107(3), e935-e946. DOI: 10.1210/clinem/dgab816
[20]Spindler M, Palombo M, Zhang H, Thiel CM. Dysfunction of the hypothalamic-pituitary-adrenal axis and its influence on aging: The role of the hypothalamus. Scientific Reports, 2023, 13(1), 33922. DOI: 10.1038/s41598-023-33922-5
[21]Carrascosa MJ, Andres A, Ros M, Bogonez E, Arribas C, Fernandez-Agullo T, et al. Development of insulin resistance during aging: Involvement of central processes and role of adipokines. Current Protein and Peptide Science, 2011, 12(4), 305-315. DOI: 10.2174/138920311795906655
[22]Xu FZ, Dou L, Yu DN, Wu X, Liu LT, Man Y, et al. A novel “endocrine hormone”: The diverse role of extracellular vesicles in multiorgan insulin resistance. International Journal of Medical Sciences, 2024, 21(11), 2081. DOI: 10.7150/ijms.97217
[23]Anawalt BD, Matsumoto AM. Aging and androgens: Physiology and clinical implications. Reviews in Endocrine & Metabolic Disorders, 2022, 23, 1123-1137. DOI: 10.1007/s11154-022-09765-2
[24]Brown ED, Obeng-Gyasi B, Hall JE, Shekhar S. The thyroid hormone axis and female reproduction. International journal of molecular sciences, 2023, 24(12), 9815. DOI: 10.3390/ijms24129815
[25]Zhu J, Zhou YE, Jin BH, Shu J. Role of estrogen in the regulation of central and peripheral energy homeostasis: From a menopausal perspective. Therapeutic Advances in Endocrinology and Metabolism, 2023, 14, 20420188231199359. DOI: 10.1177/20420188231199359
[26]Shaulson ED, Cohen AA, Picard M. The brain-body energy conservation model of aging. Nature Aging, 2024, 4, 1354. DOI: 10.1038/s43587-024-00716-x
[27]Balough JL, Dipali SS, Velez KM, Kumar TR, Duncan FE. Hallmarks of female reproductive aging in physiologic aging mice. Nature Aging, 2024, 4, 1711-1730. DOI: 10.1038/s43587-024-00769-y
[28]Zaidi M, Yuen T, Kim S. Pituitary crosstalk with bone, adipose tissue and brain. Nature Reviews Endocrinology, 2023, 19, 708-721. DOI: 10.1038/s41574-023-00894-5
[29]Bohm M, Stegemann A, Paus R, Kleszczynski K, Maity P, Wlaschek M, et al. Endocrine controls of skin aging. Endocrine Reviews, 2024, 46(3), 349-375. DOI: 10.1210/endrev/bnae034
[30]Powanda MC, Moyer ED. A brief, highly selective history of acute phase proteins as indicators of infection, inflammation and injury. Inflammopharmacology, 2021, 29(3), 897-901. DOI: 10.1007/s10787-021-00820-z.
[31]Yoo ES, Yu J, Sohn J. Neuroendocrine control of appetite and metabolism. Experimental & Molecular Medicine, 2021, 53, 505-516. DOI: 10.1038/s12276-021-00597-9
[32]Skorka-Majewicz M, Goschorska M, Zwierello W, Baranowska-Bosiacka I, Styburski D, Kapczuk P, et al. Effect of fluoride on endocrine tissues and their secretory functions--review. Chemosphere, 2020, 260, 127565. DOI: 10.1016/j.chemosphere.2020.127565
[33]Shou J, Chen PJ, Xiao WH. Mechanism of increased risk of insulin resistance in aging skeletal muscle. Diabetology & Metabolic Syndrome, 2020, 12(1), 14. DOI: 10.1186/s13098-020-0523-x
[34]Palmer AK, Jensen MD. Metabolic changes in aging humans: Current evidence and therapeutic strategies. The Journal of Clinical Investigation, 2022, 132(16), e158451. DOI: 10.1172/jci158451
[35]Hassan S, Thacharodi A, Priya A, Meenatchi R, Hegde TA, Thangamani R, et al. Endocrine disruptors: Unravelling the link between chemical exposure and women's reproductive health. Environmental Research, 2023, 241, 117385. DOI: 10.1016/j.envres.2023.117385
[36]Little AG, Seebacher F. Endocrine responses to environmental variation. Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 2024, 379(1898), 20220515. DOI: 10.1098/rstb.2022.0515
[37]Yang JL, Hodara E, Sriprasert I, Shoupe D, Stanczyk FZ. Estrogen deficiency in the menopause and the role of hormone therapy: Integrating the findings of basic science research with clinical trials. Menopause, 2024, 31(10), 926-939. DOI: 10.1097/GME.0000000000002407
[38]Rahman MU, Ullah MW, Shah JA, Sethupathy S, Bilal H, Abdikakharovich SA, et al. Harnessing the power of bacterial laccases for xenobiotic degradation in water. Science of The Total Environment, 2024, 918, 170498. DOI: 10.1016/j.scitotenv.2024.170498
[39]Zhao Y, Fent K. Endogenous hormones matter in evaluation of endocrine disruptive effects mediated by nuclear receptors. Eco-Environment & Health, 2024, 3, 257. DOI: 10.1016/j.eehl.2024.04.006
[40]Shi YC, Ma JS, Li SJ, Liu C, Liu YN, Chen J, et al. Sex difference in human diseases: Mechanistic insights and clinical implications. Signal Transduction and Targeted Therapy, 2024, 9, 238. DOI: 10.1038/s41392-024-01929-7
[41]Barth C, Crestol A, Lange AG de, Galea LAM. Sex steroids and the female brain across the lifespan: Insights into risk of depression and Alzheimer's disease. The Lancet. Diabetes & Endocrinology, 2023, 11(12), 926-941. DOI: 10.1016/s2213-8587(23)00224-3
[42]Gilmer G, Hettinger ZR, Tuakli-Wosornu YA, Skidmore ER, Silver JK, Thurston RC, et al. Female aging: When translational models don't translate. Nature Aging, 2023, 3, 1500-1508. DOI: 10.1038/s43587-023-00509-8
[43]Dong L, Teh DBL, Kennedy BK, Huang Z. Unraveling female reproductive senescence to enhance healthy longevity. Cell Research, 2023, 33, 11-29. DOI: 10.1038/s41422-022-00718-7
[44]Bianchi VE, Bresciani E, Meanti R, Rizzi L, Omeljaniuk RJ, Torsello A. The role of androgens in women's health. Pharmacological Research, 2021, 171, 105758. DOI: 10.1016/j.phrs.2021.105758
[45]Biagetti B, Puig-Domingo M. Age-related hormones changes and its impact on health status and lifespan. Aging and Disease, 2023, 14(3), 605-620. DOI: 10.14336/AD.2022.1109
[46]Coggins C, Patel S, Nigam SN, Rai V. Hormonal changes during aging and their effects on quality of life. Exploration of Endocrine and Metabolic Diseases, 2025, 2, 101447. DOI: 10.37349/eemd.2025.101447
[47]Conover CA, Oxvig C. The IGF system and aging. Endocrine reviews, 2025, 46(2) 214-223. DOI: 10.1210/endrev/bnae029
[48]Latek D, Tutuncu Y. Linking the endocrine system with immunity. Frontiers in Endocrinology, 2025, 16, 1638965. DOI: 10.3389/fendo.2025.1638965
[49]Pataky MW, Young WF, Nair KS. Hormonal and metabolic changes of aging and the influence of lifestyle modifications. Mayo Clinic Proceedings, 2021, 96(3), 788-814. DOI: 10.1016/j.mayocp.2020.07.033
[50]Rosen R, Yarmush ML. Current trends in anti-aging strategies. Annual Review of Biomedical Engineering, 2023, 25, 363-385. DOI: 10.1146/annurev-bioeng-120122-123054
[51]Abdulrasak MA. Biochemistry of Aging: Decoding the complex pathways to longevity. Tropical Journal of Natural Product Research, 2024, 8(9), 8269-8274. DOI: 10.26538/tjnpr/v8i9.3
[52]Qoura LA, Churov AV, Maltseva ON, Arbatskiy MS, Tkacheva ON. The aging interactome: From cellular dysregulation to therapeutic frontiers in age-related diseases. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2025, 1872(1), 168060. DOI: 10.1016/j.bbadis.2025.168060
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Copyright (c) 2026 Aisha Abdullahi Armayau (Author)
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