What does the research say about immunosenescence?
Immunosenescence is the age-associated decline in immune function, marked by thymic involution, reduced T-cell output, chronic low-grade inflammation and the expansion of senescent immune cell subsets. This page summaris
Immunosenescence is the formal term for the progressive, age-associated decline in immune system function. It is not a disease and not a single marker; it is a composite phenotype. The literature groups its features into innate and adaptive arms, and the recurring components are thymic involution, reduced naive T-cell production, telomere shortening in immune cells, chronic low-grade inflammation, and the expansion of senescent immune cell subsets [1]. The term is used across immunology, geroscience and clinical specialties including rheumatology and oncology, and it appears in the literature alongside the broader concept of cellular senescence, which can occur in any organ system during ageing [3].
The mechanistic work in this area centres on thymic output and the T-cell compartment, with the thymus as the principal tissue of interest and the peptide hormone thymosin alpha-1 (Tα1) as one of the most studied modulators of that output [2].
Research Studies
Immunosenescence and systemic lupus erythematosus
A review of immunosenescence in systemic lupus erythematosus (SLE) reported that many immunological alterations seen in SLE resemble those of physiological ageing. The mechanisms reviewed included telomere shortening, chronic low-grade inflammation, thymic dysfunction, and expansion of senescent immune cell subsets. The review noted that these age-associated immune phenotypes emerge early in SLE and contribute to disease activity, organ damage and long-term outcomes, including cardiovascular complications [1]. This is a review of human disease literature, not a controlled trial of any compound.
Thymosin alpha-1 and thymic involution
Ageing is characterised by immune decline attributed mainly to thymic involution, the age-related shrinkage of the thymus, which reduces T-cell production and is associated with chronic inflammation and increased susceptibility to age-related disease. Thymosin alpha-1, a peptide hormone produced by the thymus, has been described as immunomodulatory, anti-inflammatory and antioxidant. Preclinical and clinical studies report that Tα1 can stimulate T-cell differentiation, enhance thymic output, and modulate dendritic cell and macrophage activity, and that it can improve vaccine response in elderly populations and mitigate immunosenescence [2].
Thymosin alpha-1 and stage I non-small cell lung cancer
A registered clinical trial is exploring the effect of thymosin alpha-1 on postoperative peripheral blood circulating tumour cells and immunosenescence in patients with early-stage non-small cell lung cancer (NSCLC) [4]. This is a trial record; results are not reported in the evidence available here.
Nicotinamide mononucleotide and immunosenescence in metabolic disorders
A placebo-controlled clinical trial investigated the effect of nicotinamide mononucleotide (NMN) supplementation on immunosenescence in middle-aged and elderly individuals with metabolic disorders, with glucose and lipid metabolism among the outcomes assessed. The rationale given is that metabolic disorders can themselves trigger ageing processes, and that cellular senescence occurs across body systems, with senescence of the immune system termed immunosenescence [3].
Nicotinamide mononucleotide and mesenchymal stem cell senescence
In work using D-galactose-induced ageing mice and cellular senescence models, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were studied as an anti-ageing approach. The ageing microenvironment was reported to induce oxidative stress and senescence in transplanted hUC-MSCs, impairing their capacity to delay immunosenescence, and NMN co-treatment was investigated as a means of enhancing their anti-ageing capacity [9]. This finding is from animal and in vitro models.
Alpha-ketoglutarate and surgical stress in older patients
Coronary artery bypass grafting (CABG) is performed in approximately 400,000 patients in the United States each year and invokes a large surgical stress response, with systemic epinephrine increasing 33-fold and norepinephrine increasing 3-fold. Local tissue injury produces sterile inflammation and release of damage-associated molecular patterns, which activate neutrophils and a cascade of cytokines, complement and coagulation changes. A registered trial, AEGIS, is examining alpha-ketoglutarate in this geroprotection context [5]. This is a trial record; no outcome data are reported here.
Taxifolin and ergothioneine and immune biomarkers in healthy volunteers
Immune function varies across the lifecourse, with a well-understood decline with age resulting in impaired vaccination responses and increased risk of infection and severe complications. A registered trial in healthy volunteers is assessing taxifolin and ergothioneine against immune biomarkers, noting that diet supplies the energy and building blocks for immune mediator synthesis and can indirectly affect immune function via the gut microbiome [6]. This is a trial record.
Comparison of studied agents and models
| Agent | Model or population | Reported focus |
|---|---|---|
| Thymosin alpha-1 | Preclinical and clinical studies; elderly vaccine recipients [2] | T-cell differentiation, thymic output, dendritic cell and macrophage activity |
| Thymosin alpha-1 | Stage I NSCLC, postoperative [4] | Circulating tumour cells and immunosenescence |
| Nicotinamide mononucleotide | Middle-aged and elderly with metabolic disorders [3] | Immunosenescence, glucose and lipid metabolism |
| Nicotinamide mononucleotide | D-galactose-aged mice and cell models [9] | hUC-MSC senescence and oxidative stress |
| Alpha-ketoglutarate | Older CABG patients [5] | Surgical stress and geroprotection |
| Taxifolin / ergothioneine | Healthy volunteers [6] | Immune biomarkers |
Related mechanisms reported in the literature
Additional reports describe immunosenescence in specific contexts. In menopause, progressive estrogen depletion is associated with mitochondrial dysfunction, oxidative stress, chronic inflammation, genomic instability and immunosenescence [7]. Bone metabolism is regulated by immune cells through cytokine secretion and cell interactions, and disruption of that regulation by inflammation, autoimmunity or ageing drives pathological bone disease [8]. Irisin, a muscle-secreted myokine induced by exercise, has been described as a molecular bridge between muscle activity and the immune system, potentially modulating the transition toward immunosenescence and host vulnerability to acute systemic inflammation [10].
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Sources
- [1] Immunosenescence in systemic lupus erythematosus: Mechanisms, clinical consequences, and therapeutic implications
- [2] Aging and Thymosin Alpha-1
- [3] The Impact of Nicotinamide Mononucleotide Sustained-release Tablets on Immunosenescence and Metablism in Middle-aged and Elderly Individuals With Metabolic Disorders
- [4] Immuno-effect of Tα1 for Stage I NSCLC
- [5] Alpha Ketoglutarate Enhances Geroprotection In Surgery (AEGIS)
- [6] Taxifolin/Ergothioneine and Immune Biomarkers in Healthy Volunteers (TaxEr)
- [7] Nicotinamide Adenine Dinucleotide and Its Anti-aging Effects in the Context of Longevity and Menopause
- [8] Advances in the study of the role of bone immunity in physiological and pathological processes related to bone metabolism
- [9] Enhancing the anti-ageing capacity of hUC-MSCs via NMN co-treatment in D-galactose-induced ageing mice and cellular senescence models
- [10] Irisin in the aging immune landscape: A new player at the crossroads of immunosenescence and sepsis