Inflammaging

Original Editor - Lucinda hampton

Top Contributors - Lucinda hampton and Tolulope Adeniji  

Introduction

Old age is typified by an atypical low-grade, chronic, and "sterile" inflammatory state, know as inflammaging, ie. an age-related increase in systemic chronic inflammatory status. Several contributory factors to inflammaging include accumulated oxidative stress, changes within the inflammatory cytokine network, and cellular senescence with advancing age. These changes are associated with a loss of physical and immune resilience, amplifying the risk of being malnourished and frail and significantly contributing to the pathogenesis of many age-related diseases and to the progression of the ageing process.

Immune response

The salient points of inflammaging are:

1. Immunosenescence, an age associated process that impairs the immune function, is the main driver of inflammaging. With immunosenescence thymic involution occurs and reduces the pool of naïve T cells and amplifies the oligo-clonal expansion of memory T cells. These events will cause a reduced immune reserve diversity, leading to reduced ability to fight infections and increased cancer incidence
2. With aging, the accumulated exposure to free radicals produced by environmental factors including cigarette smoke, dietary factors, and ionizing radiations generates “oxidative stress” in the older person. This causes oxidative protein damage and harmful DNA changes which contributes to, for example, cancer progression through upregulating inflammatory responses.
3. Ageing in all tissues is associated with increased cellular senescence, a stress-response process by which damaged cells leave the cell cycle permanently and produce a pro-inflammatory senescence-associated secretory phenotype (SASP). These senescent cells accumulate with advancing age causing a pro inflammatory profile.
4. Decreased sex steroid hormone levels, after menopause or andropause, is another mechanism for the age-associated increase in systemic IL-6 activity, a pro inflammatory cytokine.
5. Degenerative joint disease is common in older adults, and the explanation may be related to aging of the joint cells resulting from the secretion of inflammatory mediators

Aging leads to perturbations in cellular homeostasis leads to inflammaging that results in pro-inflammatory cytokine secretion.

Viewing

This 2 minute video gives a simple introduction to the topic.

Diet

Balanced-nutrition

We can influence the amount of inflammaging in our bodies by heading dietary advice.

1. The kind of diet adhered to affects inflammaging directly. Healthy diets that include a higher intake of whole grains, vegetables and fruits, nuts and fish appear to counteract the low grade age-related inflammation, for example the Mediterranean diet. Such diets are associated with lower concentrations of inflammatory mediators, like C-reactive protein (CRP) and Tumor Necrosis Factor-α (TNF-α), that are hallmarks of inflammaging.
2. An emerging area of research is the microbiome-ageing interaction. Studies show dysbiosis plays a role in sub-optimal metabolism, immune function and brain function, which all contribute to the poor health and impaired well-being associated with ageing. Modulation of the gut microbiota is showing promising results in some disorders.
3. Contributors to inflammaging include adipose tissue and dietary fat. Excessive intake of lipids can modify the gut microbiota contributing to metabolic endotoxemia, whilst omega 3 fatty acids (in eg fish oils) seem to attenuate this change. The aging-related increase and redistribution of body fat stand (higher fat content) allows the infiltration of M1 macrophages and T lymphocytes. These immune cells, and the adipocytes themselves, release cytokines and chemokines increasing the inflammatory profile.

Exercise

Exercise

It is known that decreased physical activity has a detrimental role in muscle quality, and inappropriate nutritional habits hasten the process of immunosenescence and inflammaging.

1. Inflammaging has been associated with increased risk for skeletal muscle wasting, strength loss and functional impairments. Studies performed in animals and cell cultures show increased concentrations of pro-inflammatory cytokines (such as IL-6 and TNF-α as well as increased levels of C-reactive protein).
2. Physical activity can alter the systemic inflammation of older adults regardless of their level of intensity, reducing blood fibrinogen and C-reactive protein levels.
3. It has also been proven that exercise intervention may mediate inflammaging by reducing visceral fat mas; inhibiting TNF-α; myokine release-IL-6; increasing IL-10 release, and increasing the body's antioxidant capacity, among others.

Senolytics

Wild Berries: High in Quercetin

Red wine

A new class of agents, which annihilate senescent cells (SC) named ‘senolytics’ are hoped to bring about a reduction in the inflammatory load in the older person. Genetic evidence has demonstrated that clearance of SCs can delay aging and extend healthspan. Senolytics thus far tested include dasatinib (D, a FDA-approved tyrosine kinase inhibitor), quercetin (Q, a flavonoid present in many fruits and vegetables), navitoclax and fistein (F, a flavonoid, found in many fruits and vegetables including strawberries apples, and grapes). Results from trials to date are helping to determine the safety and efficacy of senolytics, which may transform the care and treatment of older adults and patients with multiple chronic diseases. Pre-clinical studies conducted in mice have shown senolytics destroy senescent cells resulting in delaying, preventing or alleviating multiple age- and senescence-related conditions, for example frailty, cataracts, age-related osteoporosis, age-related muscle loss, radiation-induced damage, cardiac dysfunction, vascular dysfunction and calcification, pulmonary fibrosis, hepatic steatosis, metabolic syndrome, diabetes and dementia.

• An example of a natural source of a senolytic is Quercetin. It is found naturally in many plant-based foods, particularly in the outer layer or peel. Good food sources include: blueberries, asparagus, cherries, tomatoes, red apples, red grapes, kale.
• Red wine: Resveratrol is a powerful antioxidant that neutralizes free radicals produced during everyday bodily functions, as as such is a senolytic. The American Journal of Hypertension, found that resveratrol (in this case from red wine) decreases the risk of heart disease among other common health concerns. Moderate red wine consumption seems to bear the potential of being health promoting, whereas excessive alcohol consumption can induce liver cirrhosis and cancer. Further research and more in vivo studies are needed, before resveratrol (or red wine) sees clinical application as a pharmacological drug in human medicine.