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Hedi Raizer

Journal 5 min read

Which peptides are studied in relation to inflammaging?

A research-supply overview of peptides and related compounds investigated in inflammaging models, including myokines, irisin, BDNF, IL-6, IGF-1, cathepsin B, GDF-15, and alpha-ketoglutarate, with evidence from animal and

peptides-pro Editorial

Which peptides are studied in relation to inflammaging?

Inflammaging is the chronic, low-grade, sterile inflammation that develops with age and is implicated in multiple age-related pathologies. In the research literature, several peptides and related compounds are studied for their roles in inflammaging, including myokines such as irisin/FNDC5, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), cathepsin B, and growth differentiation factor-15 (GDF-15) [2]. These molecules are investigated as mediators of the muscle-brain axis and as biomarkers of sarcopenia, a condition in which inflammaging is a central mechanism [2][3]. Additionally, alpha-ketoglutarate (AKG) is being studied in clinical trials for its potential geroprotective effects in surgical stress, a model of acute inflammation [4]. Other compounds, such as omega-3 fatty acids, vitamin D3, and vitamin K2, are examined within the "Heart-Brain-Bone" axis framework, which includes inflammaging as a shared regulator [1].

The work centres on the muscle-brain axis and the interplay between mitochondrial dysfunction, cellular senescence, and chronic low-grade inflammation, with a focus on myokines and exerkines as signalling molecules [2][3].

Research Studies

Irisin/FNDC5 and the muscle-brain axis in ageing

Irisin, encoded by the FNDC5 gene, is a myokine studied for its role in mediating communication between skeletal muscle and the brain. In the context of inflammaging, irisin is investigated as a potential modulator of neuroinflammation and cognitive decline associated with sarcopenia. The narrative review by [2] synthesises evidence that progressive sarcopenia disrupts myokine signalling, including irisin, which may accelerate cognitive impairment. However, the evidence is largely observational and mechanistic, with limited causal data from human interventions.

BDNF and neuroinflammation in sarcopenia

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that also functions as a myokine. It is studied in relation to inflammaging because of its role in neuronal plasticity and its potential to counteract neuroinflammatory processes. The review [2] discusses how BDNF, along with other myokines, may link muscle health to brain function, and how sarcopenia-related reductions in BDNF could contribute to cognitive decline. Most evidence comes from animal models and cross-sectional human studies, so causality remains uncertain.

IL-6 as a dual-role cytokine in inflammaging

Interleukin-6 (IL-6) is a cytokine with both pro- and anti-inflammatory properties. In the context of inflammaging, IL-6 is often measured as a biomarker of chronic inflammation. The review [2] includes IL-6 among myokines that mediate muscle-brain communication. Additionally, the clinical study [6] aims to characterise glucose metabolism and inflammaging in elderly subjects, correlating circulating interleukins, including IL-6, with muscle mass and function. The evidence supports IL-6 as a marker of inflammaging, but its precise role in mediating age-related muscle wasting is still under investigation.

IGF-1 and anabolic resistance in ageing muscle

Insulin-like growth factor-1 (IGF-1) is a peptide hormone with anabolic effects on muscle. In inflammaging research, IGF-1 is studied for its potential to counteract anabolic resistance, a feature of sarcopenia. The review [2] lists IGF-1 as a myokine involved in muscle-brain crosstalk. However, the relationship between IGF-1, inflammaging, and muscle function is complex, and evidence from human studies is limited.

Cathepsin B and exercise-induced neurogenesis

Cathepsin B is a lysosomal protease that is also secreted by muscle during exercise. It is studied as an exerkine that may mediate some of the beneficial effects of exercise on the brain, including potential anti-inflammatory actions. The review [2] includes cathepsin B among the myokines linking muscle to brain health. Most evidence comes from animal studies, and its role in human inflammaging is not yet established.

GDF-15 as a stress-induced myokine

Growth differentiation factor-15 (GDF-15) is a member of the TGF-beta superfamily and is induced by cellular stress and inflammation. It is studied as a biomarker of ageing and inflammaging, and as a myokine involved in muscle-brain signalling. The review [2] includes GDF-15 in its synthesis of myokines that may mediate the muscle-brain axis. Elevated GDF-15 levels have been associated with various age-related conditions, but its causal role in inflammaging remains to be determined.

Alpha-ketoglutarate and surgical stress in older adults

Alpha-ketoglutarate (AKG) is a metabolite that has been studied for its geroprotective potential. The clinical trial [4] is investigating AKG in older patients undergoing coronary artery bypass grafting (CABG), a procedure that triggers a massive surgical stress response and systemic inflammation. The trial hypothesises that AKG may mitigate the inflammatory cascade associated with surgery, which is a model of acute inflammaging. This study is ongoing, and results are not yet available.

Omega-3, vitamin D3, and vitamin K2 in the Heart-Brain-Bone axis

Long-chain omega-3 fatty acids, vitamin D3, and vitamin K2 are lipid-soluble nutrients that have been studied for their roles in modulating inflammaging within the proposed "Heart-Brain-Bone" axis [1]. This framework integrates evidence from cardiovascular, neurocognitive, and bone health studies, suggesting that these nutrients may influence shared regulators of inflammation resolution and vascular integrity. However, the axis is a conceptual framework, not a validated physiological entity, and the evidence for these nutrients in inflammaging is derived from separate studies with varying designs [1].

Comparative overview of peptides and compounds in inflammaging research

Compound Class Primary model Key findings
Irisin/FNDC5 Myokine Animal, human observational Mediates muscle-brain crosstalk; disrupted in sarcopenia [2]
BDNF Neurotrophin/myokine Animal, human observational Supports neuronal plasticity; linked to cognitive decline in sarcopenia [2]
IL-6 Cytokine Human observational Biomarker of inflammaging; dual role in muscle [2][6]
IGF-1 Peptide hormone Animal, human observational Anabolic effects; may counteract anabolic resistance [2]
Cathepsin B Protease/exerkine Animal Exercise-induced; potential neuroprotective effects [2]
GDF-15 Myokine Human observational Stress-induced; associated with ageing [2]
Alpha-ketoglutarate Metabolite Human clinical trial (ongoing) Investigated for geroprotection in surgical stress [4]
Omega-3, Vit D3, Vit K2 Lipid-soluble nutrients Human observational, clinical Modulate inflammaging in Heart-Brain-Bone axis [1]

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