Abstract
Adult prematurely aging mice (PAM), characterized by inadequate stress response, show premature immunosenescence and shorter lifespan compared to adult exceptional non-PAM (E-NPAM). Aging can be influenced by lifestyle factors, such as social environment. The continuous cohabitation of female PAM with E-NPAM improved behavioral responses, immunity, redox state, and longevity of PAM, but caused deterioration in E-NPAM. The objective of this study was to investigate whether the social interaction of only 15 min/day for 2 months of PAM with E-NPAM, can produce that improvement in PAM without causing deterioration in E-NPAM. After that short social interaction PAM and E-NPAM were submitted to behavioral tests and peritoneal leukocytes were collected to assess immune functions, oxidative and inflammatory state parameters as well as catecholamine concentrations. The lifespan of each animal was recorded. Plasmatic concentration of oxytocin was also studied. Results showed that PAM presented better behavioral responses, immunity and oxi-inflammatory state after interacting with E-NPAM, and consequently a longer lifespan. E-NPAM, in general, did not show any changes after interaction with PAM, not affecting their longevity either. In conclusion, a short social interaction between PAM and E-NPAM could be an excellent strategy for improving the health state and longevity of PAM without causing deleterious effect on E-NPAM.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
All material used and data generated or analyzed during this study are included in this published article.
Code availability
Non applicable.
Abbreviations
- BCA:
-
Bicinchoninic acid
- BHT:
-
Butylated hydroxy-toluene
- c.p.m.:
-
Counts per minute
- CI:
-
Chemotaxis index
- ConA:
-
Concanavalin A
- DP:
-
Dopamine
- E:
-
Epinephrine
- EDTA:
-
Ethylenediaminetetraacetic acid
- E-NPAM SI:
-
E-NPAM that interacted socially (SI) 15 minutes each day with PAM
- E-NPAM:
-
Exceptional non-prematurely aging mice
- E-NPAMC:
-
E-NPAM control group
- fMLP:
-
N-Formyl methionyl-leucyl-phenylalanine
- GPx:
-
Glutathione peroxidase
- GR:
-
Glutathione reductase
- GSH:
-
Reduced glutathione
- GSSG:
-
Oxidized glutathione
- LDH:
-
Lactate dehydrogenase
- LPS:
-
Lipopolysaccharide
- MIF:
-
Macrophage migration inhibitory factor
- NADPH:
-
Nicotinamide adenine dinucleotide phosphate
- NE:
-
Norepinephrine
- NEM:
-
N-ethylmaleimide
- NK:
-
Natural killer
- OPT:
-
O-phthalaldehyde
- PAM SI:
-
PAM that interacted socially 15 minutes each day with adult animals
- PAM:
-
Prematurely aging mice
- PAMC:
-
PAM control group
- PBS:
-
Phosphate buffer saline
- PE:
-
Phagocytic efficacy
- PI:
-
Phagocytic index
- RPMI:
-
Roswll Park Mermorial Institute culture medium
- SD:
-
Standard deviation
- TBA:
-
Thiobarbituric acid
- TBARS:
-
Thiobarbituric acid reactive substances
References
Alves GJ, Palermo-Neto J (2015) Odor cues released by Ehrlich tumor-bearing mice are aversive and induce psychological stress. NeuroImmunoModulation 22(3):121–129. https://doi.org/10.1159/000358253
Baeza I, De Castro NM, Giménez-Llort L, De la Fuente M (2010) Ovariectomy, a model of menopause in rodents, causes a premature aging of the nervous and immune systems. J Neuroimmunol 219(1–2):90–99. https://doi.org/10.1016/j.jneuroim.2009.12.008
Barnes MA, Carson MJ, Nair MG (2015) Non-traditional cytokines: how catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system. Cytokine 72(2):210–219. https://doi.org/10.1016/j.cyto.2015.01.008
Bellinger DL, Millar BA, Pérez S, Carter J, Wood C, ThyagaRajan S, Molinaro C, Lubahn C, Lorton D (2008) Sympathetic modulation of immunity: relevance to disease. Cell Immunol 252(1–2):27–56. https://doi.org/10.1016/j.cellimm.2007.09.005
Berger MJ, Doherty TJ (2010) Sarcopenia: prevalence, mechanisms, and functional consequences. Interdiscip Top Gerontol 37:94–114. https://doi.org/10.1159/000319997
Boyden S (1962) The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leucocytes. J Exp Med 115(3):453–466. https://doi.org/10.1084/jem.115.3.453
Brenes GA, Penninx BW, Judd PH, Rockwell E, Sewell DD, Wetherell JL (2008) Anxiety, depression and disability across the lifespan. Aging Ment Health 12(1):158–163. https://doi.org/10.1080/13607860601124115
Cosentino M, Marino F, Bombelli R, Ferrari M, Lecchini S, Frigo G (2003) Unravelling dopamine (and catecholamine) physiopharmacology in lymphocytes: open questions. Trends Immunol 24(11):581–582. (Author reply 582–583). https://doi.org/10.1016/j.it.2003.09.002
Cruces J, Venero C, Pereda-Pérez I, De la Fuente M (2014) The effect of psychological stress and social isolation on neuroimmunoendocrine communication. Curr Pharm Des 20(29):4608–4628. https://doi.org/10.2174/1381612820666140130205822
De La Fuente M (1985) Changes in the macrophage function with aging. Comp Biochem Physiol A 81(4):935–938. https://doi.org/10.1016/0300-9629(85)90933-8
De la Fuente M (2018a) Bio-psycho-social bridge: the psychoneuroimmune system in successful aging. In: Fernández-Ballesteros R, Benetos A, Robine J (eds) The Cambridge handbook of successful aging (Cambridge handbooks in psychology). Cambridge University Press, Cambridge, pp 265–280
De la Fuente M (2018b) Oxidation and inflammation in the immune and nervous systems, a link between aging and anxiety. In: Fulop T, Franceschi C, Hirokawa K, Pawelec G (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-64597-1_115-1
De la Fuente M, Miquel J (2009) An update of the oxidationinflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des 15:3003–3026. https://doi.org/10.2174/138161209789058110
De la Fuente M, Miñano M, Manuel Victor V, Del Rio M, Ferrández MD, Díez A, Miquel J (1998) Relation between exploratory activity and immune function in aged mice: a preliminary study. Mech Ageing Dev 102(2–3):263–277. https://doi.org/10.1016/s0047-6374(98)00015-3
Detillion CE, Craft TK, Glasper ER, Prendergast BJ, DeVries AC (2004) Social facilitation of wound healing. Psychoneuroendocrinology 29(8):1004–1011. https://doi.org/10.1016/j.psyneuen.2003.10.003
Díaz-Del Cerro E, Ceprián N, Félix J, De la Fuente M (2022) A short social interaction between adult and old mice improves the homeostatic systems and increases healthy longevity. Exp Gerontol 158:111653. https://doi.org/10.1016/j.exger.2021.111653
Elabd C, Cousin W, Upadhyayula P, Chen RY, Chooljian MS, Li J, Kung S, Jiang KP, Conboy IM (2014) Oxytocin is an age-specific circulating hormone that is necessary for muscle maintenance and regeneration. Nat Commun 5:4082. https://doi.org/10.1038/ncomms5082
Flierl MA, Rittirsch D, Huber-Lang M, Sarma JV, Ward PA (2008) Catecholamines-crafty weapons in the inflammatory arsenal of immune/inflammatory cells or opening pandora’s box? Mol Med 14(3–4):195–204. https://doi.org/10.2119/2007-00105.Flierl
Garrido A, Cruces J, Ceprián N, De la Fuente M (2018a) Improvements in behavior and immune function and increased life span of old mice cohabiting with adult animals. J Gerontol A 73(7):873–881. https://doi.org/10.1093/gerona/gly043
Garrido A, Cruces J, Ceprián N, Hernández-Sánchez C, De la Fuente M (2018b) Premature aging in behavior and immune functions in tyrosine hydroxylase haploinsufficient female mice. A Longitudinal Study. Brain Behav Immun 69:440–455. https://doi.org/10.1016/j.bbi.2018.01.003
Garrido A, Cruces J, Ceprián N, Vara E, De la Fuente M (2019a) Oxidative-inflammatory stress in immune cells from adult mice with premature aging. Int J Mol Sci 20(3):769. https://doi.org/10.3390/ijms20030769
Garrido A, Cruces J, Ceprián N, Corpas I, Tresguerres JA, De la Fuente M (2019b) Social environment improves immune function and redox state in several organs from prematurely aging female mice and increases their lifespan. Biogerontology 20(1):49–69. https://doi.org/10.1007/s10522-018-9774-4
Garrido A, Cruces J, Ceprián N, Díaz-Del Cerro E, Félix J, De la Fuente M (2020) The ratio of prematurely aging to non-prematurely aging mice cohabiting, conditions their behavior, immunity and lifespan. J Neuroimmunol 343:577240. https://doi.org/10.1016/j.jneuroim.2020.577240
Goodson JL, Thompson RR (2010) Nonapeptide mechanisms of social cognition, behavior and species-specific social systems. Curr Opin Neurobiol 20(6):784–794. https://doi.org/10.1016/j.conb.2010.08.020
Guayerbas N, Puerto M, Víctor VM, Miquel J, De la Fuente M (2002) Leukocyte function and life span in a murine model of premature immunosenescence. Exp Gerontol 37:249–256. https://doi.org/10.1016/s0531-5565(01)00190-5
Hamasato EK, de Lima AP, de Oliveira AP, dos Santos Franco AL, de Lima WT, Palermo-Neto J (2014) Cohabitation with a sick partner increases allergic lung inflammatory response in mice. Brain Behav Immun 42:109–117. https://doi.org/10.1016/j.bbi.2014.06.001
Harati H, Barbelivien A, Herbeaux K, Muller MA, Engeln M, Kelche C, Cassel JC, Majchrzak M (2013) Lifelong environmental enrichment in rats: impact on emotional behavior, spatial memory vividness, and cholinergic neurons over the lifespan. Age (dordr) 35(4):1027–1043. https://doi.org/10.1007/s11357-012-9424-8
Hashimoto Y, Arai I, Takano N, Tanaka M, Nakaike S (2006) Induction of scratching behaviour and dermatitis in various strains of mice cohabiting with NC/Nga mice with chronic dermatitis. Br J Dermatol 154(1):28–33. https://doi.org/10.1111/j.1365-2133.2005.06879.x
Heikkinen RL, Kauppinen M (2004) Depressive symptoms in late life: a 10-year follow-up. Arch Gerontol Geriatr 38(3):239–250. https://doi.org/10.1016/j.archger.2003.10.004
Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U (2003) Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol Psychiatry 54(12):1389–1398. https://doi.org/10.1016/s0006-3223(03)00465-7
Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74(1):214–26. https://doi.org/10.1016/0003-2697(76)90326-2
Holt-Lunstad J, Smith TB, Baker M, Harris T, Stephenson D (2015) Loneliness and social isolation as risk factors for mortality: a meta-analytic review. Perspect Psychol Sci 10(2):227–237. https://doi.org/10.1177/1745691614568352
Hunsche C, Martínez de Toda I, Hernández O, Jiménez B, Díaz LE, Marcos A, De la Fuente M (2020) The supplementations with 2-hydroxyoleic acid and n-3 polyunsaturated fatty acids revert oxidative stress in various organs of diet-induced obese mice. Free Radic Res 54(6):455–466. https://doi.org/10.1080/10715762.2020.1800004
Karelina K, DeVries AC (2011) Modeling social influences on human health. Psychosom Med 73(1):67–74. https://doi.org/10.1097/PSY.0b013e3182002116
Kassed CA, Herkenham M (2004) NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety. Behav Brain Res 154(2):577–584. https://doi.org/10.1016/j.bbr.2004.03.026
Klöting I, Nitschke C, van den Brandt J (2003) Impact of genetic profiles on experimental studies: outbred versus wild rats. Toxicol Appl Pharmacol 189(1):68–71. https://doi.org/10.1016/s0041-008x(03)00099-1
Leach S, Suzuki K (2020) Adrenergic signaling in circadian control of immunity. Front Immunol 11:1235. https://doi.org/10.3389/fimmu.2020.01235
Machado TR, Alves GJ, Quinteiro-Filho WM, Palermo-Neto J (2017) Cohabitation with an Ehrlich tumor-bearing cagemate induces immune but not behavioral changes in male mice. Physiol Behav 169:82–89. https://doi.org/10.1016/j.physbeh.2016.11.022
Marino F, Cosentino M (2013) Adrenergic modulation of immune cells: an update. Amino Acids 45(1):55–71. https://doi.org/10.1007/s00726-011-1186-6
Martínez de Toda I, Maté I, Vida C, Cruces J, De la Fuente M (2016) Immune function parameters as markers of biological age and predictors of longevity. Aging (albany NY) 8(11):3110–3119. https://doi.org/10.18632/aging.101116
Martínez de Toda I, Garrido A, Vida C, Gomez-Cabrera MC, Viña J, De la Fuente M (2018) Frailty quantified by the “Valencia Score” as a potential predictor of lifespan in mice. J Gerontol A 73(10):1323–1329. https://doi.org/10.1093/gerona/gly064
Martínez de Toda I, Vida C, Sanz San Miguel L, De la Fuente M (2019) When will my mouse die? Life span prediction based on immune function, redox and behavioural parameters in female mice at the adult age. Mech Ageing Dev 182:111125. https://doi.org/10.1016/j.mad.2019.111125
Martínez de Toda I, Vida C, Garrido A, De la Fuente M (2020) redox parameters as markers of the rate of aging and predictors of life span. J Gerontol A 75(4):613–620. https://doi.org/10.1093/gerona/glz033
Massey V, Williams C (1965) On the reaction mechanism of yeast glutathione reductase. J Biol Chem 240:4470–4481
Onaka T, Takayanagi Y (2019) Role of oxytocin in the control of stress and food intake. J Neuroendocrinol 31(3):e12700. https://doi.org/10.1111/jne.12700
Orozco-Solis R, Aguilar-Arnal L (2020) Circadian regulation of immunity through epigenetic mechanisms. Front Cell Infect Microbiol 10:96. https://doi.org/10.3389/fcimb.2020.00096
Patterson AC, Veenstra G (2010) Loneliness and risk of mortality: a longitudinal investigation in Alameda County, California. Soc Sci Med 71(1):181–186. https://doi.org/10.1016/j.socscimed.2010.03.024
Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14(3):149–167. https://doi.org/10.1016/0165-0270(85)90031-7
Pérez-Álvarez L, Baeza I, Arranz L, Marco EM, Borcel E, Guaza C, Viveros MP, De la Fuente M (2005) Behavioral, endocrine and immunological characteristics of a murine model of premature aging. Dev Comp Immunol 29(11):965–976. https://doi.org/10.1016/j.dci.2005.02.008
Pittman QJ (2011) A neuro-endocrine-immune symphony. J Neuroendocrinol 23(12):1296–1297. https://doi.org/10.1111/j.1365-2826.2011.02176.x
Riddell SR (2018) Adrenaline fuels a cytokine storm during immunotherapy. Nature 564(7735):194–196. https://doi.org/10.1038/d41586-018-07581-w
Rosenne E, Sorski L, Shaashua L, Neeman E, Matzner P, Levi B, Ben-Eliyahu S (2014) In vivo suppression of NK cell cytotoxicity by stress and surgery: glucocorticoids have a minor role compared to catecholamines and prostaglandins. Brain Behav Immun 37:207–219. https://doi.org/10.1016/j.bbi.2013.12.007
Salchner P, Lubec G, Singewald N (2004) Decreased social interaction in aged rats may not reflect changes in anxiety-related behaviour. Behav Brain Res 151(1–2):1–8. https://doi.org/10.1016/j.bbr.2003.07.002
Savikko N, Routasalo P, Tilvis RS, Strandberg TE, Pitkälä KH (2005) Predictors and subjective causes of loneliness in an aged population. Arch Gerontol Geriatr 41(3):223–233. https://doi.org/10.1016/j.archger.2005.03.002
Scanzano A, Cosentino M (2015) Adrenergic regulation of innate immunity: a review. Front Pharmacol 6:171. https://doi.org/10.3389/fphar.2015.00171
Scatliffe N, Casavant S, Vittner D, Cong X (2019) Oxytocin and early parent-infant interactions: a systematic review. Int J Nurs Sci 6(4):445–453. https://doi.org/10.1016/j.ijnss.2019.09.009
Seeman TE, Crimmins E (2001) Social environment effects on health and aging: integrating epidemiologic and demographic approaches and perspectives. Ann N Y Acad Sci 954:88–117. https://doi.org/10.1111/j.1749-6632.2001.tb02749.x
Steptoe A, Shankar A, Demakakos P, Wardle J (2013) Social isolation, loneliness, and all-cause mortality in older men and women. Proc Natl Acad Sci USA 110(15):5797–5801. https://doi.org/10.1073/pnas.1219686110
Sundström G, Fransson E, Malmberg B, Davey A (2009) Loneliness among older Europeans. Eur J Ageing 6(4):267. https://doi.org/10.1007/s10433-009-0134-8
Victor C, Scambler S, Shah S, Cook D, Harris T, Rink E, De Wilde S (2002) Has loneliness amongst older people increased? An investigation into variations between cohorts. Ageing Soc 22(5):585–597. https://doi.org/10.1017/S0144686X02008784
Vida C, De la Fuente M (2013) Stress-related behavioural responses, immunity and ageing in animal models. Immunosenescence. Springer, New York, pp 125–144
Viveros MP, Arranz L, Hernanz A, Miquel J, De la Fuente M (2007) A model of premature aging in mice based on altered stressrelated behavioral response and immunosenescence. Neuroimmunomodulation 14(3–4):157–62. https://doi.org/10.1159/000110640
Wahl HW, Lang FR (2003) Aging in context across the adult life course: integrating physical and social environmental research perspectives. In: Wahl HW, Scheidt RJ, Windley PG (eds) Annual review of gerontology and geriatrics. Focus on aging in context: socio-physical environments, vol 23. Springer, New York, pp 1–34
Wilson RS, Krueger KR, Arnold SE, Schneider JA, Kelly JF, Barnes LL, Tang Y, Bennett DA (2007) Loneliness and risk of Alzheimer disease. Arch Gen Psychiatry 64(2):234–240. https://doi.org/10.1001/archpsyc.64.2.234
Windle RJ, Kershaw YM, Shanks N, Wood SA, Lightman SL, Ingram CD (2004) Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo-pituitary-adrenal activity. J Neurosci 24(12):2974–2982. https://doi.org/10.1523/JNEUROSCI.3432-03.2004
Zambrana C, Marco EM, Arranz L, de Castro NM, Viveros MP, de la Fuente M (2007) Influence of aging and enriched environment on motor activity and emotional responses in mice. Ann N Y Acad Sci 1100:543–552. https://doi.org/10.1196/annals.1395.060
Acknowledgements
We would also like to thank Allison Teichman for her critical proofreading of the English language of the manuscript.
Funding
This work was supported by the Research Group UCM (910379) to Mónica De la Fuente.
Author information
Authors and Affiliations
Contributions
Conceptualization: MF; methodology: ED-DC and JF; data curation: ED-DC; writing—original draft preparation: ED-DC; writing—review and editing: MF, ED-DC and JF. All authors have read and agreed to the published version of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no have conflict of interest.
Ethical approval
The protocol was approved by the Committee on Animal Experimentation of the Complutense University of Madrid (PROEX. 224.0/21)., and the animals were treated in accordance with the guidelines of Royal Decree 53/2013 of 1 February 2013 (BOE No. 34) on the protection of animals used for experimentation and other scientific purposes.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Cerro, E.DD., Félix, J. & De la Fuente, M. Prematurely aging female mice improve their behavioural response, immunity, redox state, and lifespan after a short social interaction with non-prematurely aging mice. Biogerontology 23, 307–324 (2022). https://doi.org/10.1007/s10522-022-09968-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-022-09968-9