Thread by @GrimaldesJ

Epidemiological studies show that older adults are the most affected by this pandemic, which makes chronological age a risk factor in SC2

Senescence👉stable growth arrest induced👉 cells reach the end of their replication potential or are exposed to various stressors👉infection.

pubmed.ncbi.nlm.nih.gov/18692159/

Main molecular pro-inflammatory pathways involved in aging and age-related diseases👇

The role of inflammation in pathophysiological process and the possible action of CR and exercise👇

Like other tissues, the immune system is characterized by the decline of its functions with age (immunosenescence), reflected not only in a higher prevalence of cancer, autoimmune diseases and other chronic diseases, but also in an increased susceptibility to infections.👇

academic.oup.com/cid/article/39…

Impact of infectious disease in the elderly population on health care services (solid arrows) and factors contributing to an increase in the burden of infectious disease in elderly individuals (patterned arrows). These circumstances create a vicious circle, limiting resources👇

Viral infections are also known as stressors that can induce senescence in different cell lines. Dengue virus can cause senescence in endothelial cells and measles virus leads to cellular senescence in normal and cancerous fibroblasts.
genesdev.cshlp.org/content/27/21/…

Aging decreases the positive regulation molecules essential for T-cell priming and also reduces the production of antiviral interferon (IFN) by alveolar macrophages and dendritic cells (DC).

geriatric.theclinics.com/article/S0749-…

In summary, deterioration in the number, function and activation of cells involved in the immune response and aging of hematopoietic stem cells are the main immune system phenotypes associated with immunosenescence.

sciencedirect.com/science/articl…

sciencedirect.com/science/articl…

These changes lead 👉"inflammatory" process, in which low-grade inflammation is present in later life and is associated with a worsening of chronic progressive medical conditions, such as HF, and the onset of aging, diseases related to the CNS (Alzheimer's disease).👇

Immunosencescence and inflammaging create a vicious cycle creating an environment favorable for the development of neurodegenerative diseases.

aging-us.com/article/103989…

PART 2

In humans, senescent T cells predict the development of hyperglycemia.

diabetes.diabetesjournals.org/content/68/1/1…

Circulating senescent T cells are linked with systemic inflammation and lesion size during human cutaneous leishmaniasis.

frontiersin.org/articles/10.33…

The accumulation of senescent endothelial cells is a big contributing factor to atherosclerosis and cardiovascular disease

sciencedirect.com/science/articl…

Senescent cells in bone marrow promote immunosenescence.

onlinelibrary.wiley.com/doi/full/10.11…

nature.com/articles/bjc20…

✅ Here are some causes of senescent cell formation:

*Obesity and excess body fat drive senescence and inhibit neurogenesis👉Fat cells, particularly visceral fat, tend to accumulate macrophages and secrete pro-inflammatory cytokines.

sciencedirect.com/science/articl…

*Impaired immune surveillance accelerates accumulation of senescent cells and aging👉 This increases inflammation and cytotoxicity.

sciencedirect.com/science/articl…

*T cell dysregulation and T cell aging👉Immunosenescence is associated with reduced CD4+/CD8+ ratio, impaired helper T cell development, reduced cytotoxicity of natural killer cells, excessive CD8+ T cells inhibiting anti-viral defense and hampered response to antigens.

pubmed.ncbi.nlm.nih.gov/15268751/

pubmed.ncbi.nlm.nih.gov/12915213/

*Inflammation, pro-inflammatory cytokines and senescence👉It spreads like wildfire to neighbouring cells and shortens telomeres. Telomere erosion leaves you more susceptible to cellular senescence.

pubmed.ncbi.nlm.nih.gov/17943234/

*DNA damage sets off cell senescence👉This results from oxidative stress and activates a protein called p53. It’s a tumor suppressor that tries to prevent the senescent cells from becoming malignant and cancerous.

pubmed.ncbi.nlm.nih.gov/18574463/?dopt…

*Metabolic dysfunction drives senescence👉Hyperglycemia causes cellular senescence and inflammaging, which accelerates senescence. Elevated glucose makes macrophages induces SASP and proinflammatory cytokine release, thus promoting low grade inflammation and senescence.

pubmed.ncbi.nlm.nih.gov/24996978/

pubmed.ncbi.nlm.nih.gov/31676687/

sciencedirect.com/science/articl…

*High nutrient signaling via insulin/IGF-1 and mTOR accelerate cell replication and senescence. They also prevent the clearance of dead cells by inhibiting autophagy. Overactivation of mTOR contributes to SASP.

pubmed.ncbi.nlm.nih.gov/26147250/?dopt…

PART 3

If you want to live longer as well as slow down immunosenescence, then you want to eliminate senescent cells on a regular basis.

Potential strategy to prevent cellular senescence and remove zombie cells👇

✔️FOXO Protein Activation 👉FOXO proteins are transcription factors that regulate longevity in response to stress. FOXO4 peptide can selectively target senescent cells.

febs.onlinelibrary.wiley.com/doi/full/10.10…

✔️ Fasting for 48 hours👉elevates FOXO1,3 and 4 by 1.5 fold and refeeding drops it back to baseline. Calorie restriction increases sirtuins as well as FOXO factors.

frontiersin.org/articles/10.33…

✔️Acute exercis👉Acute exercise increases FOXO1 phosphorylation, improves insulin sensitivity and promotes mitochondrial biogenesis increases FOXO1 phosphorylation, improves insulin sensitivity and promotes mitochondrial biogenesis.

ncbi.nlm.nih.gov/pmc/articles/P…

✔️Taking a sauna or other means of increasing core body temperature and exercising can promote FOXO activation.

✔️Beta-hydroxybutyrate (BHB)👉is one of the ketone bodies that increases FOXO3 and lowers oxidative stress. BHB can also delay vascular aging through endothelial cells,perhaps by reducing senescence.

ncbi.nlm.nih.gov/pmc/articles/P…

✔️Heat and Cold Exposure👉Heat shock proteins trigger autophagy and help to clear misfolded proteins. Saunas and ice baths also stimulate the lymph and flush out toxins.

ncbi.nlm.nih.gov/pmc/articles/P…

✔️Vitamin D and magnesium👉Activation of the vitamin D receptor (VDR) can oppose the synthesis of SASP proteins, such as IL-6 and IL-8, via inhibition of p38 MAP kinase. The VDR is activated by calcitriol (the active form of vitamin D) and magnesium is required for this to occur.

pubmed.ncbi.nlm.nih.gov/16618780/

magnesium deficiency increases the risk of oxidative damage to DNA, which is the primary cause of cellular senescence.

pubmed.ncbi.nlm.nih.gov/24753742/

✔️ Zinc and Copper👉Zinc can antagonize the toxic heavy metal cadmium, an inducer of oxidative stress that plays a role in DNA damage and premature cellular aging. Copper deficiency also increases oxidative damage.

scientificamerican.com/article/heavy-…

PART 4

✅There are specific compounds and drugs that can selectively kill senescent cells called senolytics. They target senescent cells as well as stimulate other related pathways such as Nrf2 and autophagy that help to clear them out.

ncbi.nlm.nih.gov/pmc/articles/P…

Senolytics have shown promise in the treatment of heart failure, lung disease, 🧠Alzheimer’s and promote longevity.

pubmed.ncbi.nlm.nih.gov/30936558/

✔️Quercetin🧅👉flavonoid found in apples, broccoli, onions, cabbage, and other vegetables. It activates Nrf2 and has anti-inflammatory properties.

sciencedirect.com/science/articl…

✔️Fisetin🍓👉naturally occuring flavone that has senolytic properties, is found in fruits and vegetables like apples, strawberries, onions and cucumbers.

liebertpub.com/doi/10.1089/ar…

pubmed.ncbi.nlm.nih.gov/28273655/

✔️Azithromycin and Roxithromycin💊👉that target senescent cells. Remove up to 97% of senescent cells, which is a 25-fold reduction in senescence.

pubmed.ncbi.nlm.nih.gov/30428454/

✔️EGCG👉green tea🍵👉suppresses premature senescence and induces senescent cell death. It also promotes FOXO3, the main FOXO protein associated with longevity.

cancerres.aacrjournals.org/content/67/12/…

pubmed.ncbi.nlm.nih.gov/30456590/

✔️Allicin🧄👉 is an organosulfur compound found in garlic. It can reduce oxidative stress and can kill senescent cells.

wjgnet.com/1007-9327/full…

✔️Berberine🌾👉is an alkaloid found in barberry and other plants. It has potent anti-diabetic effects that promote autophagy and suppress p53.

spandidos-publications.com/10.3892/or.201…