Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2019, Vol. 10 Issue (3) : 676-683     DOI: 10.14336/AD.2019.0315
Conceptual Article |
A Microcirculatory Theory of Aging
Kunlin Jin*
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, TX 76107, USA
Download: PDF(322 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Aging is the progressive decline of physiological functions necessary for survival and reproduction. In gaining a better understanding of the inevitable aging process, the hope is to preserve, promote, or delay healthy aging through the treatment of common age-associated diseases. Although there are theories that try to explain the aging process, none of them seem to fully satisfy. Microcirculation describes blood flow through the capillaries in the circulatory system. The main functions of the microcirculation are the delivery of oxgen and nutrients and the removal of CO2, metabolic debris, and toxins. The microcirculatory impairment or dysfunction over time will result in the accumulation of toxic products and CO2 and loss of nutrition supplementation and O2 in corresponding tissue systems or internal organs, which eventually affect normal tissue and organ functions, leading to aging. Therefore, I propose a microcirculatory theory of aging: aging is the process of continuous impairment of microcirculation in the body.

Keywords aging      theory      microcirculation      impairment      lifespan     
Corresponding Authors: Jin Kunlin   
About author:

These authors contributed equally to this study.

Issue Date: 28 May 2019
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Kunlin Jin
Cite this article:   
Kunlin Jin. A Microcirculatory Theory of Aging[J]. Aging and disease, 2019, 10(3): 676-683.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2019.0315     OR     http://www.aginganddisease.org/EN/Y2019/V10/I3/676
[1] Jin K (2010). Modern Biological Theories of Aging. Aging Dis, 1:72-74.
[2] Reid L, Meyrick B (1982). Microcirculation: definition and organization at tissue level. Ann N Y Acad Sci, 384:3-20.
[3] Popel AS, Torres Filho IP, Johnson PC, Bouskela E (1988). A new scheme for hierarchical classification of anastomosing vessels. Int J Microcirc Clin Exp, 7:131-138.
[4] den Uil CA, Klijn E, Lagrand WK, Brugts JJ, Ince C, Spronk PE, et al. (2008). The microcirculation in health and critical disease. Prog Cardiovasc Dis, 51:161-170.
[5] Jaffe R, Charron T, Puley G, Dick A, Strauss BH (2008). Microvascular obstruction and the no-reflow phenomenon after percutaneous coronary intervention. Circulation, 117:3152-3156.
[6] Rhodin JA (1967). The ultrastructure of mammalian arterioles and precapillary sphincters. J Ultrastruct Res, 18:181-223.
[7] Sakai T, Hosoyamada Y (2013). Are the precapillary sphincters and metarterioles universal components of the microcirculation? An historical review. J Physiol Sci, 63:319-331.
[8] Smaje L, Zweifach BW, Intaglietta M (1970). Micropressures and capillary filtration coefficients in single vessels of the cremaster muscle of the rat. Microvasc Res, 2:96-110.
[9] Rhodin JA (1968). Ultrastructure of mammalian venous capillaries, venules, and small collecting veins. J Ultrastruct Res, 25:452-500.
[10] Krogh A (1919). The supply of oxygen to the tissues and the regulation of the capillary circulation. J Physiol, 52:457-474.
[11] Tsai AG, Friesenecker B, Mazzoni MC, Kerger H, Buerk DG, Johnson PC, et al. (1998). Microvascular and tissue oxygen gradients in the rat mesentery. Proc Natl Acad Sci U S A, 95:6590-6595.
[12] Pittman RN (2000). Oxygen supply to contracting skeletal muscle at the microcirculatory level: diffusion vs. convection. Acta Physiol Scand, 168:593-602.
[13] Pittman RN (2011). Oxygen gradients in the microcirculation. Acta Physiol (Oxf), 202:311-322.
[14] Scallan J, Huxley VH, Korthuis RJ. 2010. In Capillary Fluid Exchange: Regulation, Functions, and Pathology. San Rafael (CA).
[15] Granger DN, Barrowman JA (1983). Microcirculation of the alimentary tract I. Physiology of transcapillary fluid and solute exchange. Gastroenterology, 84:846-868.
[16] Langer HF, Chavakis T (2009). Leukocyte-endothelial interactions in inflammation. J Cell Mol Med, 13:1211-1220.
[17] Ohashi KL, Tung DK, Wilson J, Zweifach BW, Schmid-Schonbein GW (1996). Transvascular and interstitial migration of neutrophils in rat mesentery. Microcirculation, 3:199-210.
[18] Sonntag WE, Lynch CD, Cooney PT, Hutchins PM (1997). Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. Endocrinology, 138:3515-3520.
[19] Wilkinson JH, Hopewell JW, Reinhold HS (1981). A quantitative study of age-related changes in the vascular architecture of the rat cerebral cortex. Neuropathol Appl Neurobiol, 7:451-462.
[20] Hutchins PM, Lynch CD, Cooney PT, Curseen KA (1996). The microcirculation in experimental hypertension and aging. Cardiovasc Res, 32:772-780.
[21] Amenta F, Cavallotti D, Del Valle M, Mancini M, Naves FJ, Vega JA, et al. (1995). Age-related changes in brain microanatomy: sensitivity to treatment with the dihydropyridine calcium channel blocker darodipine (PY 108-068). Brain Res Bull, 36:453-460.
[22] Jucker M, Battig K, Meier-Ruge W (1990). Effects of aging and vincamine derivatives on pericapillary microenvironment: stereological characterization of the cerebral capillary network. Neurobiol Aging, 11:39-46.
[23] Shao WH, Li C, Chen L, Qiu X, Zhang W, Huang CX, et al. (2010). Stereological investigation of age-related changes of the capillaries in white matter. Anat Rec (Hoboken), 293:1400-1407.
[24] Klein AW, Michel ME (1977). A morphometric study of the neocortex of young adult and old maze-differentiated rats. Mech Ageing Dev, 6:441-452.
[25] Buchweitz-Milton E, Weiss HR (1987). Perfused capillary morphometry in the senescent brain. Neurobiol Aging, 8:271-276.
[26] Casey MA, Feldman ML (1985). Aging in the rat medial nucleus of the trapezoid body. III. Alterations in capillaries. Neurobiol Aging, 6:39-46.
[27] Hinds JW, McNelly NA (1982). Capillaries in aging rat olfactory bulb: a quantitative light and electron microscopic analysis. Neurobiol Aging, 3:197-207.
[28] Xu X, Wang B, Ren C, Hu J, Greenberg DA, Chen T, et al. (2017). Age-related Impairment of Vascular Structure and Functions. Aging Dis, 8:590-610.
[29] Villena A, Vidal L, Diaz F, Perez De Vargas I (2003). Stereological changes in the capillary network of the aging dorsal lateral geniculate nucleus. Anat Rec A Discov Mol Cell Evol Biol, 274:857-861.
[30] Meier-Ruge W, Schulz-Dazzi U (1987). Effects of brovincamine on the stereological parameters of corticocerebral capillaries. Life Sci, 40:943-949.
[31] Black JE, Polinsky M, Greenough WT (1989). Progressive failure of cerebral angiogenesis supporting neural plasticity in aging rats. Neurobiol Aging, 10:353-358.
[32] Bar T (1978). Morphometric evaluation of capillaries in different laminae of rat cerebral cortex by automatic image analysis: changes during development and aging. Adv Neurol, 20:1-9.
[33] Chen JJ, Rosas HD, Salat DH (2011). Age-associated reductions in cerebral blood flow are independent from regional atrophy. Neuroimage, 55:468-478.
[34] Sturrock RR (1977). Quantitative and morphological changes in neurons and neuroglia in the indusium griseum of aging mice. J Gerontol, 32:647-658.
[35] Rakusan K, Nagai J (1994). Morphometry of arterioles and capillaries in hearts of senescent mice. Cardiovasc Res, 28:969-972.
[36] Bell MA, Ball MJ (1981). Morphometric comparison of hippocampal microvasculature in ageing and demented people: diameters and densities. Acta Neuropathol, 53:299-318.
[37] Bell MA, Ball MJ (1986). The correlation of vascular capacity with the parenchymal lesions of Alzheimer’s disease. Can J Neurol Sci, 13:456-461.
[38] Bell MA, Ball MJ (1990). Neuritic plaques and vessels of visual cortex in aging and Alzheimer’s dementia. Neurobiol Aging, 11:359-370.
[39] Abernethy WB, Bell MA, Morris M, Moody DM (1993). Microvascular density of the human paraventricular nucleus decreases with aging but not hypertension. Exp Neurol, 121:270-274.
[40] Mann DM, Eaves NR, Marcyniuk B, Yates PO (1986). Quantitative changes in cerebral cortical microvasculature in ageing and dementia. Neurobiol Aging, 7:321-330.
[41] Meier-Ruge W, Hunziker O, Schulz U, Tobler HJ, Schweizer A (1980). Stereological changes in the capillary network and nerve cells of the aging human brain. Mech Ageing Dev, 14:233-243.
[42] Brown WR, Moody DM, Thore CR, Challa VR, Anstrom JA (2007). Vascular dementia in leukoaraiosis may be a consequence of capillary loss not only in the lesions, but in normal-appearing white matter and cortex as well. J Neurol Sci, 257:62-66.
[43] Farkas E, de Vos RA, Donka G, Jansen Steur EN, Mihaly A, Luiten PG (2006). Age-related microvascular degeneration in the human cerebral periventricular white matter. Acta Neuropathol, 111:150-157.
[44] Hunziker O, Al SA, Schulz U, Schweizer A (1978). Architecture of cerebral capillaries in aged human subjects with hypertension. Adv Neurol, 20:471-477.
[45] Hunziker O, Abdel’Al S, Schulz U (1979). The aging human cerebral cortex: a stereological characterization of changes in the capillary net. J Gerontol, 34:345-350.
[46] Li L, Mac-Mary S, Sainthillier JM, Nouveau S, de Lacharriere O, Humbert P (2006). Age-related changes of the cutaneous microcirculation in vivo. Gerontology, 52:142-153.
[47] Frontera WR, Hughes VA, Fielding RA, Fiatarone MA, Evans WJ, Roubenoff R (2000). Aging of skeletal muscle: a 12-yr longitudinal study. J Appl Physiol (1985), 88:1321-1326.
[48] Russell JA, Kindig CA, Behnke BJ, Poole DC, Musch TI (2003). Effects of aging on capillary geometry and hemodynamics in rat spinotrapezius muscle. Am J Physiol Heart Circ Physiol, 285:H251-258.
[49] Stanton AV, Wasan B, Cerutti A, Ford S, Marsh R, Sever PP, et al. (1995). Vascular network changes in the retina with age and hypertension. J Hypertens, 13:1724-1728.
[50] Rivard A, Fabre JE, Silver M, Chen D, Murohara T, Kearney M, et al. (1999). Age-dependent impairment of angiogenesis. Circulation, 99:111-120.
[51] Shimada T, Takeshita Y, Murohara T, Sasaki K, Egami K, Shintani S, et al. (2004). Angiogenesis and vasculogenesis are impaired in the precocious-aging klotho mouse. Circulation, 110:1148-1155.
[52] Davis MJ, Lawler JC (1958). The capillary circulation of the skin; some normal and pathological findings. AMA Arch Derm, 77:690-703.
[53] Lombard WP (1912). The blood pressure in the arterioles, capillaries, and small veins of the human skin. AJP-Legacy, 29:335-362.
[54] Gutterman DD, Chabowski DS, Kadlec AO, Durand MJ, Freed JK, Ait-Aissa K, et al. (2016). The Human Microcirculation: Regulation of Flow and Beyond. Circ Res, 118:157-172.
[55] Tsuchida Y (1993). The effect of aging and arteriosclerosis on human skin blood flow. J Dermatol Sci, 5:175-181.
[56] Dinenno FA, Jones PP, Seals DR, Tanaka H (1999). Limb blood flow and vascular conductance are reduced with age in healthy humans: relation to elevations in sympathetic nerve activity and declines in oxygen demand. Circulation, 100:164-170.
[57] Khalil A, Humeau-Heurtier A, Mahe G, Abraham P (2015). Laser speckle contrast imaging: age-related changes in microvascular blood flow and correlation with pulse-wave velocity in healthy subjects. J Biomed Opt, 20:051010.
[58] Proctor DN, Shen PH, Dietz NM, Eickhoff TJ, Lawler LA, Ebersold EJ, et al. (1998). Reduced leg blood flow during dynamic exercise in older endurance-trained men. J Appl Physiol (1985), 85:68-75.
[59] Sarabi M, Millgard J, Lind L (1999). Effects of age, gender and metabolic factors on endothelium-dependent vasodilation: a population-based study. J Intern Med, 246:265-274.
[60] Dinenno FA, Seals DR, DeSouza CA, Tanaka H (2001). Age-related decreases in basal limb blood flow in humans: time course, determinants and habitual exercise effects. J Physiol, 531:573-579.
[61] Richardson D, Shewchuk R (1980). Comparison of calf muscle blood flow responses to rhythmic exercise between mean age 25- and 74-year-old men. Proc Soc Exp Biol Med, 164:550-555.
[62] Magnusson G, Kaijser L, Isberg B, Saltin B (1994). Cardiovascular responses during one- and two-legged exercise in middle-aged men. Acta Physiol Scand, 150:353-362.
[63] Jasperse JL, Seals DR, Callister R (1994). Active forearm blood flow adjustments to handgrip exercise in young and older healthy men. J Physiol, 474:353-360.
[64] Olive JL, DeVan AE, McCully KK (2002). The effects of aging and activity on muscle blood flow. Dyn Med, 1:2.
[65] Martin AJ, Friston KJ, Colebatch JG, Frackowiak RS (1991). Decreases in regional cerebral blood flow with normal aging. J Cereb Blood Flow Metab, 11:684-689.
[66] Moeller JR, Ishikawa T, Dhawan V, Spetsieris P, Mandel F, Alexander GE, et al. (1996). The metabolic topography of normal aging. J Cereb Blood Flow Metab, 16:385-398.
[67] Farkas E, Luiten PG (2001). Cerebral microvascular pathology in aging and Alzheimer’s disease. Prog Neurobiol, 64:575-611.
[68] Krejza J, Mariak Z, Walecki J, Szydlik P, Lewko J, Ustymowicz A (1999). Transcranial color Doppler sonography of basal cerebral arteries in 182 healthy subjects: age and sex variability and normal reference values for blood flow parameters. AJR Am J Roentgenol, 172:213-218.
[69] Hagstadius S, Risberg J (1989). Regional cerebral blood flow characteristics and variations with age in resting normal subjects. Brain Cogn, 10:28-43.
[70] Cavusoglu M, Pfeuffer J, Ugurbil K, Uludag K (2009). Comparison of pulsed arterial spin labeling encoding schemes and absolute perfusion quantification. Magn Reson Imaging, 27:1039-1045.
[71] Shin W, Horowitz S, Ragin A, Chen Y, Walker M, Carroll TJ (2007). Quantitative cerebral perfusion using dynamic susceptibility contrast MRI: evaluation of reproducibility and age- and gender-dependence with fully automatic image postprocessing algorithm. Magn Reson Med, 58:1232-1241.
[72] Wong EC, Buxton RB, Frank LR (1998). Quantitative imaging of perfusion using a single subtraction (QUIPSS and QUIPSS II). Magn Reson Med, 39:702-708.
[73] Ye FQ, Mattay VS, Jezzard P, Frank JA, Weinberger DR, McLaughlin AC (1997). Correction for vascular artifacts in cerebral blood flow values measured by using arterial spin tagging techniques. Magn Reson Med, 37:226-235.
[74] Akiyama H, Meyer JS, Mortel KF, Terayama Y, Thornby JI, Konno S (1997). Normal human aging: factors contributing to cerebral atrophy. J Neurol Sci, 152:39-49.
[75] Meltzer CC, Cantwell MN, Greer PJ, Ben-Eliezer D, Smith G, Frank G, et al. (2000). Does cerebral blood flow decline in healthy aging? A PET study with partial-volume correction. J Nucl Med, 41:1842-1848.
[76] Martin WR, Baker RP, Grubb RL, Raichle ME (1984). Cerebral blood volume, blood flow, and oxygen metabolism in cerebral ischaemia and subarachnoid haemorrhage: an in-vivo study using positron emission tomography. Acta Neurochir (Wien), 70:3-9.
[77] Meltzer CC, Kinahan PE, Greer PJ, Nichols TE, Comtat C, Cantwell MN, et al. (1999). Comparative evaluation of MR-based partial-volume correction schemes for PET. J Nucl Med, 40:2053-2065.
[78] Ohata M, Sundaram U, Fredericks WR, London ED, Rapoport SI (1981). Regional cerebral blood flow during development and ageing of the rat brain. Brain, 104:319-332.
[79] Noda A, Ohba H, Kakiuchi T, Futatsubashi M, Tsukada H, Nishimura S (2002). Age-related changes in cerebral blood flow and glucose metabolism in conscious rhesus monkeys. Brain Res, 936:76-81.
[80] Sonntag WE, Eckman DM, Ingraham J, Riddle DR. 2007. Regulation of Cerebrovascular Aging. In Brain Aging: Models, Methods, and Mechanisms. Riddle D.R., editor. Boca Raton (FL).
[81] Jani B, Rajkumar C (2006). Ageing and vascular ageing. Postgrad Med J, 82:357-362.
[82] Edul VS, Enrico C, Laviolle B, Vazquez AR, Ince C, Dubin A (2012). Quantitative assessment of the microcirculation in healthy volunteers and in patients with septic shock. Crit Care Med, 40:1443-1448.
[83] Goldman D, Bateman RM, Ellis CG (2006). Effect of decreased O2 supply on skeletal muscle oxygenation and O2 consumption during sepsis: role of heterogeneous capillary spacing and blood flow. Am J Physiol Heart Circ Physiol, 290:H2277-2285.
[1] Fuellen Georg, Jansen Ludger, Cohen Alan A, Luyten Walter, Gogol Manfred, Simm Andreas, Saul Nadine, Cirulli Francesca, Berry Alessandra, Antal Peter, Köhling Rüdiger, Wouters Brecht, Möller Steffen. Health and Aging: Unifying Concepts, Scores, Biomarkers and Pathways[J]. Aging and disease, 2019, 10(4): 883-900.
[2] Xu Dingqiao, Liao Shanting, Li Pei, Zhang Qian, Lv Yan, Fu Xiaowei, Yang Minghua, Wang Junsong, Kong Lingyi. Metabolomics Coupled with Transcriptomics Approach Deciphering Age Relevance in Sepsis[J]. Aging and disease, 2019, 10(4): 854-870.
[3] Wang Min-jun, Chen Jiajia, Chen Fei, Liu Qinggui, Sun Yu, Yan Chen, Yang Tao, Bao Yiwen, Hu Yi-Ping. Rejuvenating Strategies of Tissue-specific Stem Cells for Healthy Aging[J]. Aging and disease, 2019, 10(4): 871-882.
[4] Maeso-Díaz Raquel, Ortega-Ribera Martí, Lafoz Erica, Lozano Juan José, Baiges Anna, Francés Rubén, Albillos Agustín, Peralta Carmen, García-Pagán Juan Carlos, Bosch Jaime, Cogger Victoria C, Gracia-Sancho Jordi. Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease[J]. Aging and disease, 2019, 10(4): 684-698.
[5] Chen Weidong, Wang Jinzeng, Shi Jiahao, Yang Xu, Yang Ping, Wang Ning, Yang Sai, Xie Tianpei, Yang Hua, Zhang Mengjie, Wang Haiyun, Fei Jian. Longevity Effect of Liuwei Dihuang in Both Caenorhabditis Elegans and Aged Mice[J]. Aging and disease, 2019, 10(3): 578-591.
[6] Cho Kyoungjoo. Emerging Roles of Complement Protein C1q in Neurodegeneration[J]. Aging and disease, 2019, 10(3): 652-663.
[7] Gourmelon Robin, Donadio-Andréi Sandrine, Chikh Karim, Rabilloud Muriel, Kuczewski Elisabetta, Gauchez Anne-Sophie, Charrié Anne, Brard Pierre-Yves, Andréani Raphaëlle, Bourre Jean-Cyril, Waterlot Christine, Guédel Domitille, Mayer Anne, Disse Emmanuel, Thivolet Charles, Boullay Hélène Du, Falandry Claire, Gilbert Thomas, François-Joubert Anne, Vignoles Antoine, Ronin Catherine, Bonnefoy Marc. Subclinical Hypothyroidism: is it Really Subclinical with Aging?[J]. Aging and disease, 2019, 10(3): 520-529.
[8] Chung Hae Young, Kim Dae Hyun, Lee Eun Kyeong, Chung Ki Wung, Chung Sangwoon, Lee Bonggi, Seo Arnold Y., Chung Jae Heun, Jung Young Suk, Im Eunok, Lee Jaewon, Kim Nam Deuk, Choi Yeon Ja, Im Dong Soon, Yu Byung Pal. Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept[J]. Aging and disease, 2019, 10(2): 367-382.
[9] Sarkar Saumyendra N., Russell Ashley E., Engler-Chiurazzi Elizabeth B., Porter Keyana N., Simpkins James W.. MicroRNAs and the Genetic Nexus of Brain Aging, Neuroinflammation, Neurodegeneration, and Brain Trauma[J]. Aging and disease, 2019, 10(2): 329-352.
[10] Cyprien Fabienne, Courtet Philippe, Maller Jerome, Meslin Chantal, Ritchie Karen, Ancelin Marie-Laure, Artero Sylvaine. Increased Serum C-reactive Protein and Corpus Callosum Alterations in Older Adults[J]. Aging and disease, 2019, 10(2): 463-469.
[11] Lana Alberto, Struijk Ellen A., Arias-Fernandez Lucía, Graciani Auxiliadora, Mesas Arthur E., Rodriguez-Artalejo Fernando, Lopez-Garcia Esther. Habitual Meat Consumption and Changes in Sleep Duration and Quality in Older Adults[J]. Aging and disease, 2019, 10(2): 267-277.
[12] Murtha Lucy A., Morten Matthew, Schuliga Michael J., Mabotuwana Nishani S., Hardy Sean A., Waters David W., Burgess Janette K., Ngo Doan TM., Sverdlov Aaron L., Knight Darryl A., Boyle Andrew J.. The Role of Pathological Aging in Cardiac and Pulmonary Fibrosis[J]. Aging and disease, 2019, 10(2): 419-428.
[13] Shetty Ashok K., Upadhya Raghavendra, Madhu Leelavathi N., Kodali Maheedhar. Novel Insights on Systemic and Brain Aging, Stroke, Amyotrophic Lateral Sclerosis, and Alzheimer’s Disease[J]. Aging and disease, 2019, 10(2): 470-482.
[14] Tingting Sui,Di Liu,Tingjun Liu,Jichao Deng,Mao Chen,Yuanyuan Xu,Yuning Song,Hongsheng Ouyang,Liangxue Lai,Zhanjun Li. LMNA-mutated Rabbits: A Model of Premature Aging Syndrome with Muscular Dystrophy and Dilated Cardiomyopathy[J]. Aging and disease, 2019, 10(1): 102-115.
[15] Dong Liu,Liqun Xu,Xiaoyan Zhang,Changhong Shi,Shubin Qiao,Zhiqiang Ma,Jiansong Yuan. Snapshot: Implications for mTOR in Aging-related Ischemia/Reperfusion Injury[J]. Aging and disease, 2019, 10(1): 116-133.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd