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aging

The process of growing old. - See biology of aging for theories of aging - also see age-related physiological changes Epidemiology: - demographically, an increase in proportion of older persons in the population (see epidemiology of aging) Physiology: - the gradual deterioration of a mature organism resulting from time-dependent, & often irreversible changes in structure that are intrinsic to a particular species (i.e. loss of post-mitotic neurons) - these changes eventually lead to a decreased ability to cope with environmental stresses, i.e. a loss of homeostasis. - as a result, the probability of death increases exponentially with time. Pathology: - hypothalamus may play a role in regulation of aging through NF-kappaB, IKK & GnRH-regulated pathways implicated in inflammation [2] - aging, stress, & depression increase expression of FKBP5 [8] - elevated expression of FKBP5 protein promotes inflammation [8] - increased expression of FKBP5 increases expression of NF-kappa B [8] - alterations in sleep occur with aging [6] - middle-age serum sodium* > 142 mmol/l may increase risk of biological aging, development of chronic diseases & death at a younger age [12] * assumed to be an indicator of clinical hydration * Hallmarks of Aging [13] - altered intercellular communication - deregulated response to nutrients - loss of stem cell function (stem cell exhaustion) - cellular senescence* - mitochondrial dysfunction - loss of proteostasis - telomere attrition - genomic instability - epigenetic alterations - chronic inflammation - dysbiosis * formation of zombie cells removed from list in 2022 * changes in brain iron & oxygen homeostasis-related gene expression noted as a hallmark of aging [14] * clearance of cell surface uPAR-containing cells with CAR T-cell therapy may prevent &/or attenuate age-related degenerative pathology [15] * Hallmarks of Health [13] - organizational features of spatial compartmentalization - maintenance of homeostasis - adequate responses to stress Clinical manifestations: - loss of hair & hair pigmentation - loss of height, bone mass, & muscle mass - increasingly thinned & wrinkled skin [3] - degree & distribution of redness & depth of facial grooves are phenotypic determinants of perceived age [4] - length of the nasolabial groove (most important) - variation/heterogeneity, amount & distribution of facial redness (hemoglobin) - depth of nasogenian groove - eyebrow position - distribution of facial melanin - facial skin roughness - also see age-related physiological changes Laboratory: - proteomic aging clock may be useful for predicting - incidence of chronic disease - age-related measures of biological, physical & cognitive function - telomere length, frailty index, reaction time - multimorbidity - all-cause mortality [19] Differential diagnosis: - geriatric disease (disease of old age) - normal aging exhibits physiological effects only when stressed [3] - obvious exceptions may be - skin aging - graying or loss of hair - postural or height changes - loss of muscle mass Evolution: - according to the theory of evolution, life arose from primordial soup when information representing life was able to replicate faster than the environment destroyed it [17] - thus began evolution - the organization of information diversified giving rise to the origin of species - some species adapted to preserve an individual for longer periods of time under pressures of survival of the species [18] - humans in their past were under pressure to select for increased reproductive fitness in individuals with increased longevity - thus human aging or its antithesis longevity has evolved; it is not fixed [9] * the molecules of life are discussed elsewhere, see - the biology of aging - evolutionary biology of longevity Notes: - quantification of aging rates in young individuals [5] - before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline & brain aging, self-reported worse health, & looked older [5] - cancer survivors are subject to an increased rate of aging with associated increase in all-cause & cancer-specific mortality [10] - investigational treatment of aging through removal of senescent cells targeting cell-surface uPAR [15]

Related

age-related physiological changes biological age biology of aging circulating plasma factors in cellular senescence death elderly (senior citizen) epidemiology of aging geriatrics gerontology life expectancy longevity neuropsychiatric features of aging psychosocial theories of aging

Specific

brain aging healthy (successful) aging; sustained independence senescence

General

pathologic process physiologic process

References

  1. Stedman's Medical Dictionary 27th ed, Williams & Wilkins, Baltimore, 1999
  2. Cai D et al Hypothalamic Programming of Systemic Aging Involving IKK NF-kB and GnRH. Albert Einstein College of Medicine http://www.eurekalert.org/pub_releases/2013-05/aeco-brm042913.php - Zhang G, Li J, Purkayastha S, Tang Y Hypothalamic programming of systemic ageing involving IKK-beta, NF-kappaB and GnRH. Nature. 2013 May 1 PMID: 23636330 - Gabuzda D and Yankner BA. Physiology: Inflammation links ageing to the brain. Nature 2013 May 9; 497:197. PMID: 23636321
  3. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  4. Coma M et al. Methods for diagnosing perceived age on the basis of an ensemble of phenotypic features. Clin Cosmet Investig Dermatol 2014 Apr 17; 7:133 PMID: 24790464 http://www.dovepress.com/methods-for-diagnosing-perceived-age-on-the-basis-of-an-ensemble-of-ph-peer-reviewed-article-CCID
  5. Belsky DW et al. Quantification of biological aging in young adults. Proc Natl Acad Sci U S A 2015 Jul 28; 112:E4104 PMID: 26150497 http://www.pnas.org/content/112/30/E4104
  6. Mander BA, Winer JR, Walker MP Sleep and Human Aging. (Review) Neuron 94(1):19-36. April 5, 2017 PMID: 28384471 http://www.cell.com/neuron/abstract/S0896-6273(17)30088-0
  7. Barzilai N, Cuervo AM, Austad S. Aging as a Biological Target for Prevention and Therapy. JAMA. Published online September 17, 2018. PMID: 30242337 https://jamanetwork.com/journals/jama/fullarticle/2703112 - Tchkonia T, Kirkland JL Aging, Cell Senescence, and Chronic Disease. Emerging Therapeutic Strategies. JAMA. Published online September 17, 2018. PMID: 30242336 https://jamanetwork.com/journals/jama/fullarticle/2703113 - Olshansky SJ From Lifespan to Healthspan. JAMA. Published online September 17, 2018. PMID: 30242384 https://jamanetwork.com/journals/jama/fullarticle/2703114
  8. Zannas AS, Jia M, Hafner K et al. Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-kappa-B driven inflammation and cardiovascular risk. Proc Natl Acad Sci U S A. 2019 Jun 4;116(23):11370-11379. PMID: 31113877 Free PMC Article https://www.pnas.org/content/116/23/11370
  9. Colchero, F, Aburto JM, Archie EA et al. The long lives of primates and the 'invariant rate of ageing' hypothesis. Nat Commun 12, 3666 (2021) PMID: 34135334 https://www.nature.com/articles/s41467-021-23894-3
  10. Zhang D, Leeuwenburgh C, Zhou D et al Analysis of Biological Aging and Risks of All-Cause and Cardiovascular Disease- Specific Death in Cancer Survivors. JAMA Netw Open. 2022;5(6):e2218183. June 22 PMID: 35731518 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793435
  11. Wajngarten M Is There Hope in the Fight Against Aging? Medscape. December 19, 2022 https://www.medscape.com/viewarticle/985809
  12. Dmitrieva NI, Gagarin A, Liu D et al Middle-age high normal serum sodium as a risk factor for accelerated biological aging, chronic diseases, and premature mortality. eBioMedicine. January 02, 2023 https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00586-2/fulltext
  13. Lopez-Otin C, Blasco MA, Partridge L et al The Hallmarks of Aging. Cell. 2013 Jun 6; 153(6): 1194-1217 PMID: 23746838 PMCID: PMC3836174 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836174/ - Lopez-Otin C, Blasco MA, Partridge L et al Hallmarks of Aging: An expanding universe. Cell. 2022 Dec 26:S0092-8674(22)01377-0 PMID: 36599349 Review. https://www.cell.com/action/showPdf?pii=S0092-8674%2822%2901377-0
  14. Lee S et al. Cell-specific dysregulation of iron and oxygen homeostasis as a novel pathophysiology in PSP. Ann Neurol 2022 Oct 30; [e-pub]. PMID: 36309960 https://onlinelibrary.wiley.com/doi/10.1002/ana.26540
  15. Amor C, Fernandez-Maestre I, Chowdhury S et al Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nat Aging. 2024 Jan 24. PMID: 38267706 https://www.nature.com/articles/s43587-023-00560-5
  16. Ramakrishnan V Why We Die: The New Science of Aging and the Quest for Immortality Hardcover - March 19 2024 https://www.amazon.com/Why-We-Die-Science-Immortality/dp/0063113279
  17. Cutler RG, The Evolutionary Biology of Senescence. In: Behnke, J.A., Finch, C.E., Moment, G.B. (eds). The Biology of Aging, Springer, Boston, MA. 1978 https://doi.org/10.1007/978-1-4613-3994-6_20
  18. Darwin C On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. John Murray, Albemarle Street. London. 1859 - Wikipedia: On the Origin of Species https://en.wikipedia.org/wiki/On_the_Origin_of_Species
  19. Argentieri MA et al. Proteomic aging clock predicts mortality and risk of common age-related diseases in diverse populations. Nat Med 2024 Sep; 30:2450 https://www.nature.com/articles/s41591-024-03164-7