The network and the remodeling theories of aging: historical background and new perspectives
Abstract
Two general theories, i.e. "the network theory of aging" (1989) and "the remodeling theory of aging" (1995), as well as their implications, new developments, and perspectives are reviewed and discussed. Particular attention has been paid to illustrate: (i) how the network theory of aging fits with recent data on aging and longevity in unicellular organisms (yeast), multicellular organisms (worms), and mammals (mice and humans); (ii) the evolutionary and experimental basis of the remodeling theory of aging (immunological, genetic, and metabolic data in healthy centenarians, and studies on the evolution of the immune response, stress and inflammation) and its recent development (the concepts of "immunological space" and "inflamm-aging"); (iii) the profound relationship between these two theories and the data which suggest that aging and longevity are related, in a complex way, to the capability to cope with a variety of stressors.
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TIS is believed to be a major driving force of frailty and other AEs in adults owing to its detrimental effect on tissue function via chronic inflammation, similar to 'inflammaging'.
“As in children and adolescents, TIS is also believed to be a major driving force of frailty and other AEs in adults owing to its detrimental effect on tissue function via chronic inflammation, similar to 'inflammaging' , which is a chronic mild inflammatory process that develops with age 198,200,201 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [201]
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BackgroundSgarbi, G., Matarrese, P., Pinti, M., Lanzarini, C., Ascione, B., Gibellini, L., Dika, E., Patrizi, A., Tommasino, C., Capri, M., et al. (2014) · Aging · doi:10.18632/aging.100654 · Cited by 90 · see citing works
Self-citationImmunoproteasomes and immunosenescence
Mishto, M., Santoro, A., Bellavista, E., Bonafè, M., Monti, D., & Franceschi, C. (2003) · Ageing Research Reviews · doi:10.1016/s1568-1637(03)00030-8 · Cited by 86 · see citing works
Self-citationLifelong aerobic exercise protects against inflammaging and cancer
Nilsson, M. I., Bourgeois, J. M., Nederveen, J. P., Leite, M. R., Hettinga, B. P., Bujak, A. L., May, L. L., Lin, E., Crozier, M., Rusiecki, D. R., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210863 · Cited by 94 · see citing works
Franceschi, C., Valensin, S., Lescai, F., Olivieri, F., Licastro, F., Grimaldi, L. M. E., Monti, D., BENEDICTIS, G. D., & Bonafè, M. (2001) · Aging Clinical and Experimental Research · doi:10.1007/bf03351475 · Cited by 87 · see citing works
Self-citationMyeloid-derived suppressor cells (MDSC): an important partner in cellular/tissue senescence
Salminen, A., Kauppinen, A., & Kaarniranta, K. (2018) · Biogerontology · doi:10.1007/s10522-018-9762-8 · Cited by 84 · see citing works
Chemokines in CSF of Alzheimer's disease patients
Corrêa, J. D., Starling, D. S. V., Teixeira, A. L., Caramelli, P., & Silva, T. A. (2011) · Arquivos de Neuro-Psiquiatria · doi:10.1590/s0004-282x2011000400009 · Cited by 80 · see citing works
“The levels of beta-amyloid, tau and phospho-tau were determined in the CSF using the following kits: Innotest® β-Amyloid(1-42); Innotest® phospho-tau (181P) e Innotest®htauAg from Innogenetics (Gent, Belgium).”
MethodApplying hormesis in aging research and therapy
Rattan, S. (2001) · Human & Experimental Toxicology · doi:10.1191/096032701701548034 · Cited by 84 · see citing works
Glucose regulation and oxidative stress in healthy centenarians
Barbieri, M. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00153-5 · Cited by 83 · see citing works
Self-citationBerendsen, A., Santoro, A., Pini, E., Cevenini, E., Ostan, R., Pietruszka, B., Rolf, K., Cano, N., Caille, A., Lyon-Belgy, N., et al. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.10.002 · Cited by 82 · see citing works
Self-citationBiogerontology: from here to where? The Lord Cohen Medal Lecture-2011
Rattan, S. I. S. (2011) · Biogerontology · doi:10.1007/s10522-011-9354-3 · Cited by 72 · see citing works
“…space and the failure of maintenance and repair pathways (Rattan 2006). characteristics: (1) stress response (Singh et al. 2007); (2) the ability for damage prevention, repair and removal (Holliday 2006); and (3) the ability for continuous remodeling and adaptation (Franceschi et al. 2000).”
Is human immunosenescence clinically relevant? Looking for 'immunological risk phenotypes'.
Pawelec, G., Ouyang, Q., Colonna-Romano, G., Candore, G., Lio, D., & Caruso, C. (2002) · Trends in immunology · doi:10.1016/s1471-4906(02)02255-x · Cited by 79 · see citing works
Frasca, D., Diaz, A., Romero, M., Mendez, N. V., Landin, A. M., & Blomberg, B. B. (2013) · Immunity & Ageing · doi:10.1186/1742-4933-10-14 · Cited by 77 · see citing works
“Immunosenescence is associated with a low grade chronic pro-inflammatory status called inflammaging [27].”
BackgroundImpact of aging on immunity in the context of COVID-19, HIV, and tuberculosis
Grifoni, A., Alonzi, T., Alter, G., Noonan, D. M., LANDAY, A. L., Albini, A., & Goletti, D. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1146704 · Cited by 87 · see citing works
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Complexity of Anti‐immunosenescence Strategies in Humans
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Self-citationGenes, ageing and longevity in humans: Problems, advantages and perspectives
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“[234] Franceschi C, Valensin S, Bonafe M, Paolisso G, Yashin AI, Monti D, De Benedictis G.”
Self-citationChanges with ageing in several leukocyte functions of male and female rats
la Fuente, M. D., Baeza, I., Guayerbas, N., Puerto, M., Castillo, C., Salazar, V., Ariznavarreta, C., & F-Tresguerres, J. A. (2004) · Biogerontology (Dordrecht) · doi:10.1007/s10522-004-3201-8 · Cited by 76 · see citing works
“In fact, it is known that centenarians have a well-preserved immune function, and the reason for it is that they are well adapted to external and internal aggressor agents, in particular to those who act on the immune system (Franceschi et al. 2000).”
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Genetics vs. entropy: Longevity factors suppress the NF-κB-driven entropic aging process
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“A large body of research has demonstrated that the aging process is associated with the pro-inflammatory changes (e.g. Franceschi et al., 2000, 2007; Sarkar and Fisher, 2006; Salminen et al., 2008a; De Magalhaes et al., 2009).”
BackgroundBone structure and metabolism in a rodent model of male senile osteoporosis
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Hypothalamic inflammation in metabolic disorders and aging
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“However, as damage accumulates, the danger responses will become persistent and maladaptive [109].”
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“Lessons come from the field of genetics of age-related diseases, where it has been theorized and demonstrated that the association of a genetic variant with a disease can vary during the life of an individual and according to the environmental conditions that he/she encountered, strictly depending from the birth cohor…”
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Proliferation and apoptosis of human CD8+CD28+ and CD8+CD28− lymphocytes during aging
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MicroRNAs miR-155 and miR-16 decrease AID and E47 in B cells from elderly individuals
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“A low-level chronic inflammatory state is common in the elderly (13, 26), and we have shown that the inflammatory status of the individual and of the B cells themselves negatively affects B cell function (27).”
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Self-citationAdipose Tissue Inflammation Induces B Cell Inflammation and Decreases B Cell Function in Aging
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Healthy ageing, but what is health?
Rattan, S. I. S. (2013) · Biogerontology · doi:10.1007/s10522-013-9442-7 · Cited by 63 · see citing works
- Authors
- Franceschi, C., Valensin, S., Bonafè, M., Paolisso, G., Yashin, A. I., Monti, D., & De Benedictis, G.
- Affiliations
- Istituto Nazionale di Riposo e Cura per Anziani (IT)
- University of Bologna (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Max Planck Institute for Demographic Research (DE)
- University of Florence (IT)
- Corresponding author
- Franceschi, C
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 35
- Issue
- 6-7
- Pages
- 879-896
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W1984265860
- Cited by
- 335
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 10 · 2023: 12 · 2022: 10 · 2021: 17 · 2020: 14 · 2019: 15 · 2018: 17 · 2017: 23 · 2016: 16 · 2015: 16 · 2014: 15 · 2013: 16 · 2012: 16
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Aging and Gerontology Research
- Keywords
- aging, longevity, centenarians, inflammaging, stress response, inflammation, stress tolerance, unicellular organisms, yeast, Caenorhabditis elegans, mice, human
- MeSH terms
- Aging, Animals, Biological Evolution, Heat-Shock Proteins, Humans, Immune System, Inflammation, Saccharomyces cerevisiae, Mice
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