Highlights
- •Biological aging phenotypes related to specific organ/system dysfunction are termed “ageotypes”.
- •Currently, four ageotypes have been identified based on longitudinal and multi-omic data, namely the metabolic, immune, hepatic, and nephrotic, each related to a distinct organ/system dysfunction.
- •Re-analysis of these data using FLAME, a web platform for functional and literature enrichment analyses of gene datasets, led to the identification of new significantly enriched pathways and diseases.
- •Enriched pathways related mostly to inflammation/immune deregulation and, minimally, metabolic processes.
- •Disease ontology identifiers were related mostly to the brain and the nervous system.
- •Nutritional and lifestyle changes to mitigate brain inflammation and aging are proposed.
Abstract
Undeniably, biological age can significantly differ between individuals of similar
chronological age. Longitudinal, deep multi-omic profiling has recently enabled the
identification of individuals with distinct aging phenotypes, termed ‘ageotypes’.
This effort has provided a plethora of data and new insights into the diverse molecular
mechanisms presumed to drive aging. Translational opportunities stemming from this
knowledge continue to evolve, providing an opportunity for the provision of nutritional
interventions aiming to decelerate the aging process. In this framework, the contemporary
ageotypes classification was revisited via in silico analyses, with the brain and nervous system being identified as the primary targets
of age-related biomolecules, acting through inflammatory and metabolic pathways. Nutritional
and lifestyle factors affecting these pathways in the brain and central nervous system
that could help guide personalized recommendations for the attainment of healthy aging
are discussed.
Abbreviations:
BDNF (brain-derived neurotrophic factor), COL11A2 (collagen type XI alpha 2 chain), C3 (complement 3), C5 (complement 5), CRP (c-reactive protein), DASH (dietary approaches to stop hypertension), DHA (docosa-hexaenoic acid), DO (disease ontology), GO (Gene Ontology), FLAME (Functional and Literature enrichment Analysis of Multiple sEts), IL-1 (interleukin-1), IPA (Ingenuity Pathway Analysis), ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4), KEGG (Kyoto Encyclopedia of Genes and Genomes), LMICs (low- and middle-income countries), M-CSF (macrophage colony-stimulating factor), NF-κB (nuclear factor-κB), PUFA (polyunsaturated fatty acids), REAC (Reactome), SAA1 (serum amyloid A), FDR (false discovery rate), SFA (saturated fatty acids), SNP (single nucleotide polymorphism), TLR4 (toll-like receptor 4), TNF-α (tumor-necrosis factor α), WP (WikiPathways)Keywords
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References
- The aging process.Proc. Natl. Acad. Sci. U. S. A. 1981; 78: 7124-7128https://doi.org/10.1073/PNAS.78.11.7124
- Escape from epigenetic silencing of lactase expression is triggered by a single-nucleotide change.Nat. Struct. Mol. Biol. 2016; 23: 505-507https://doi.org/10.1038/nsmb.3238
- The role of nutrition in inflammaging.Ageing Res. Rev. 2022; 77: 101596https://doi.org/10.1016/J.ARR.2022.101596
- The plasma proteome is favorably modified by a high protein diet but not by additional resistance training in older adults: a 17-week randomized controlled trial.Front. Nutr. 2022; 9: 925450https://doi.org/10.3389/FNUT.2022.925450
- Long-term calorie restriction alters anxiety-like behaviour and the brain and adrenal gland transcriptomes of the ageing male rat.Nutrients. 2022; 14: 4670https://doi.org/10.3390/nu14214670
- Integrated methylome and phenome study of the circulating proteome reveals markers pertinent to brain health.Nat. Commun. 2022; 13: 4670https://doi.org/10.1038/S41467-022-32319-8
- Personal aging markers and ageotypes revealed by deep longitudinal profiling.Nat. Med. 2020; 26: 83-90https://doi.org/10.1038/S41591-019-0719-5
- FLAME: a web tool for functional and literature enrichment analysis of multiple gene lists.Biology (Basel). 2021; 10: 665https://doi.org/10.3390/BIOLOGY10070665
- Biomedical Sciences Research Center “Alexander Fleming,” Flame - Functional and Literature Enrichment analysis of multiple sets.https://bib.fleming.gr:8084/app/flame(accessed August 31, 2022)Date: 2022
- Controlling the false discovery rate: a practical and powerful approach to multiple testing.J. R. Stat. Soc. Ser. B. 1995; 57: 289-300https://doi.org/10.1111/J.2517-6161.1995.TB02031.X
- KEGG mapping tools for uncovering hidden features in biological data.Protein Sci. 2022; 31: 47-53https://doi.org/10.1002/PRO.4172
- WikiPathways: a multifaceted pathway database bridging metabolomics to other omics research.Nucleic Acids Res. 2018; 46: D661-D667https://doi.org/10.1093/NAR/GKX1064
- The reactome pathway knowledgebase 2022.Nucleic Acids Res. 2022; 50: D687-D692https://doi.org/10.1093/NAR/GKAB1028
- Reactome: a knowledge base of biologic pathways and processes.Genome Biol. 2007; 8https://doi.org/10.1186/GB-2007-8-3-R39
- Gene ontology: tool for the unification of biology.Nat. Genet. 2000; 25: 29https://doi.org/10.1038/75556
- Inflammaging: a new immune–metabolic viewpoint for age-related diseases.Nat. Rev. Endocrinol. 2018; 1410: 576-590https://doi.org/10.1038/s41574-018-0059-4
- Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans.Mech. Ageing Dev. 2007; 128: 92-105https://doi.org/10.1016/J.MAD.2006.11.016
- Inflamm-ageing.Curr. Opin. Clin. Nutr. Metab. Care. 2013; 16: 14-20https://doi.org/10.1097/MCO.0B013E32835ADA13
- Age-related diseases and clinical and public health implications for the 85 years old and over population.Front. Public Heal. 2017; 5: 335https://doi.org/10.3389/FPUBH.2017.00335/XML/NLM
- Normal aging induces changes in the brain and neurodegeneration progress: review of the structural, biochemical, metabolic, cellular, and molecular changes.Front. Aging Neurosci. 2022; 14931536https://doi.org/10.3389/FNAGI.2022.931536
- Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins.Nat. Med. 2007; 13: 1359-1362https://doi.org/10.1038/NM1653
- Identification of neurotoxic cytokines by profiling Alzheimer’s disease tissues and neuron culture viability screening.Sci. Rep. 2015; 5: 16622https://doi.org/10.1038/SREP16622
- TNF-alpha modulation for treatment of Alzheimer’s disease: a 6-month pilot study.Medscape Gen. Med. 2006; 8: 25
- Rapid cognitive improvement in Alzheimer’s disease following perispinal etanercept administration.J. Neuroinflammation. 2008; 5: 2https://doi.org/10.1186/1742-2094-5-2
- Avoiding abundance bias in the functional annotation of posttranslationally modified proteins.Nat. Methods. 2015; 1211: 1003-1004https://doi.org/10.1038/nmeth.3621
- Benjamini-hochberg method.EncyclSyst. Biol. 2013; : 78https://doi.org/10.1007/978-1-4419-9863-7_1215
- Identifying significantly impacted pathways: a comprehensive review and assessment.Genome Biol. 2019; 20: 1-15https://doi.org/10.1186/S13059-019-1790-4/FIGURES/7
- Lifestyle changes to prevent cardio- and cerebrovascular disease at midlife: a systematic review.Maturitas. 2023; 167: 60-65https://doi.org/10.1016/j.maturitas.2022.09.003
- Healthy aging diets other than the Mediterranean: a focus on the Okinawan diet.Mech. Ageing Dev. 2014; 136–137: 148-162https://doi.org/10.1016/J.MAD.2014.01.002
- Effect of a lifestyle intervention on telomere length: a systematic review and meta-analysis.Mech. Ageing Dev. 2022; 206111694https://doi.org/10.1016/J.MAD.2022.111694
- Mediterranean diet and health: a systematic review of epidemiological studies and intervention trials.Maturitas. 2020; 136: 25-37https://doi.org/10.1016/J.MATURITAS.2020.03.008
- Cognitive decline and dementia in women after menopause: prevention strategies.Maturitas. 2023; 168: 53-61https://doi.org/10.1016/J.MATURITAS.2022.10.012
- The Mediterranean dietary pattern and inflammation in older adults: a systematic review and meta-analysis.Adv. Nutr. 2021; 12: 363-373https://doi.org/10.1093/ADVANCES/NMAA116
- Effects of dietary patterns on biomarkers of inflammation and immune responses: a systematic review and meta-analysis of randomized controlled trials.Adv. Nutr. 2022; 13: 101-115https://doi.org/10.1093/ADVANCES/NMAB086
- Efficacy of n-3 fatty acid supplementation on rheumatoid arthritis' disease activity indicators: a systematic review and meta-analysis of randomized placebo-controlled trials.Crit. Rev. Food Sci. Nutr. 2022; : 1-15https://doi.org/10.1080/10408398.2022.2104210
- Effect of n-3 long-chain polyunsaturated fatty acids on mild cognitive impairment: a meta-analysis of randomized clinical trials.Eur. J. Clin. Nutr. 2020; 74: 548-554https://doi.org/10.1038/S41430-019-0544-4
- The effect of Omega-3 fatty acids on thromboxane, brain-derived neurotrophic factor, homocysteine, and vitamin D in depressive children and adolescents: randomized controlled trial.Nutrients. 2021; 13: 1095https://doi.org/10.3390/NU13041095
- Aging and infection reduce expression of specific brain-derived neurotrophic factor mRNAs in hippocampus.Neurobiol. Aging. 2012; 33 (832.e1–832.e14)https://doi.org/10.1016/J.NEUROBIOLAGING.2011.07.015
- Fish oil prevents the adrenal activation elicited by mental stress in healthy men.Diabetes Metab. 2003; 29: 289-295https://doi.org/10.1016/S1262-3636(07)70039-3
- Maintenance of NF-κB activation in T-lymphocytes and a naive T-cell population in autoimmune-prone (NZB/NZW)F1 mice by feeding a food-restricted diet enriched with n-3 fatty acids.Cell. Immunol. 2001; 213: 122-133https://doi.org/10.1006/CIMM.2001.1866
- A mechanism converting psychosocial stress into mononuclear cell activation.Proc. Natl. Acad. Sci. U. S. A. 2003; 100: 1920-1925https://doi.org/10.1073/PNAS.0438019100
- Impact of omega-3 fatty acid DHA and EPA supplementation in pregnant or breast-feeding women on cognitive performance of children: systematic review and meta-analysis.Nutr. Rev. 2021; 79: 585-598https://doi.org/10.1093/NUTRIT/NUAA060
- Fish, n-3 fatty acids, cognition and dementia risk: not just a fishy tale.Proc. Nutr. Soc. 2022; 81: 27-40https://doi.org/10.1017/S0029665121003700
- Fish, a Mediterranean source of n-3 PUFA: benefits do not justify limiting consumption.Br. J. Nutr. 2015; 113: S58-S67https://doi.org/10.1017/S0007114514003742
- Dietary n-6/n-3 ratio influences brain fatty acid composition in adult rats.Nutr. 2020; 12: 1847https://doi.org/10.3390/NU12061847
- Transgenic increase in n-3/n-6 fatty acid ratio protects against cognitive deficits induced by an immune challenge through decrease of neuroinflammation.Neuropsychopharmacology. 2015; 40: 525-536https://doi.org/10.1038/NPP.2014.196
- Evolutionary aspects of diet and essential fatty acids.World Rev. Nutr. Diet. 2001; 88: 18-27https://doi.org/10.1159/000059742
- Interplay between n-3 and n-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair.Lipids. 2017; 52: 885-900https://doi.org/10.1007/S11745-017-4292-8
- Linoleic acid-good or bad for the brain?.NPJ Sci. Food. 2020; 4https://doi.org/10.1038/S41538-019-0061-9
- Hypothalamic inflammation in the control of metabolic function.Annu. Rev. Physiol. 2015; 77: 131-160https://doi.org/10.1146/ANNUREV-PHYSIOL-021014-071656
- The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice.Gastroenterology. 2011; 141https://doi.org/10.1053/J.GASTRO.2011.04.052
- Phenolic acids and prevention of cognitive decline: polyphenols with a neuroprotective role in cognitive disorders and Alzheimer's disease.Nutrients. 2022; 14https://doi.org/10.3390/NU14040819
- Moving more, ageing happy: findings from six low- and middle-income countries.Age Ageing. 2021; 50: 488-497https://doi.org/10.1093/AGEING/AFAA137
- Exercise interventions for cognitive function in adults older than 50: a systematic review with meta-analysis.Br. J. Sports Med. 2018; 52: 154-160https://doi.org/10.1136/BJSPORTS-2016-096587
- Physical activity and muscle-brain crosstalk.Nat. Rev. Endocrinol. 2019; 15: 383-392https://doi.org/10.1038/S41574-019-0174-X
- The brain-derived neurotrophic factor Val66Met polymorphism moderates an effect of physical activity on working memory performance.Psychol. Sci. 2013; 24: 1770-1779https://doi.org/10.1177/0956797613480367
- The “Virtual digital twins” concept in precision nutrition.Adv. Nutr. 2020; 11: 1405-1413https://doi.org/10.1093/advances/nmaa089
- Genetically-guided medical nutrition therapy in type 2 diabetes mellitus and prediabetes: a series of n-of-1 superiority trials.Front. Nutr. 2022; 772243https://doi.org/10.3389/FNUT.2022.772243
- Telomere length and genetic variations affecting telomere length as biomarkers for facial regeneration with platelet-rich fibrin based on the low-speed centrifugation concept.J. Cosmet. Dermatol. 2019; 18: 408-413https://doi.org/10.1111/JOCD.12666
- Microbiota from young mice counteracts selective age-associated behavioral deficits.Nat. Aging. 2021; 18: 666-676https://doi.org/10.1038/s43587-021-00093-9
- Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain.Microbiome. 2022; 10: 68https://doi.org/10.1186/S40168-022-01243-W
Article info
Publication history
Published online: February 06, 2023
Accepted:
January 18,
2023
Received in revised form:
January 13,
2023
Received:
September 2,
2022
Identification
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