What Causes Accelerated Aging? Research on Senescent Cells

Remaining energetic and healthy is generally a goal for seniors. In this article, we will look at one of the factors that cause accelerated aging — senescent cells. Damaged cells cause visible signs of aging: liver spots, gray hair, and wrinkles. Disease, injury, and other stress factors harm cells throughout our body. Increased free radical activity contributes to accelerated aging.

Ideally, the damaged cells are removed by our immune system through a process called apoptosis. Damaged cells die, are eliminated, and are replaced by new cells.  About 1% of all of our cells are replaced daily — billions of cells.¹

Two-thirds of our body is comprised of cells. The rest is fluid (such as plasma), and calcium bone structure that exists outside of cells. Roughly 72% of the cells are fat and muscle cells (which live 12 to 50 years), and the rest are in our blood (which live 3 to 120 days), and lining our gut (which live less than a week).²

Senescent Cells

However, some cells known as senescent cells, stop dividing but don’t die and get removed. Instead, they release protein-degrading enzymes and chemicals that cause chronic low-grade inflammation. Senescent cells are a major cause of accelerated aging and the development of chronic age-related disorders. Trials with animals suggest that reducing the number of senescent cells in peoples’ bodies could extend human lives. Human trials are beginning for vision conditions such as macular degeneration, glaucoma, and diabetic retinopathy.

Senescent cells also play beneficial roles. The molecules and compounds expressed by senescent cells are called the senescent secretome. They play important roles throughout our lifespan, including in embryonic development, childbirth, and wound healing.

The process of cellular senescence produces distinct observable alterations, including profound chromosome component (chromotin) changes, expressed molecules (secretome) changes, and tumor-suppressor activation.^{3 4 5 6 7}

Cellular senescence may cause age-related conditions such as cancer, diabetes, heart disease, osteoporosis, stroke, and dementia. It is linked to losses in eyesight, mobility, and cognitive capacity.

What Safely Removes Senescent Cells?

Senolytics are compounds that safely cause senescent cells to die off. Known senolytics include the drug dasatinib and the nutrients quercetin, theaflavin, and fisetin.

There are several ongoing and planned trials of senolytic agents and therapies. One example is a cocktail of the drug dasatinib (for leukemia chemotherapy) and quercetin (found in red fruits and vegetables). Together they may clear out senescent cells. In one small human trial, the combination was used to treat a fatal and debilitating lung disease with enough success to warrant further examination⁸.

Judith Campisi is a leader in aging research and has been studying senolytic agents and their effects.  She says there are still many unanswered questions, not the least of which is how to remove the bad effects of senolytics, but retain the good effects.⁹

Herbs/nutrients that Naturally Reduce Senescence

Quercetin

Quercetin was the first nutrient to show promise as a senolytic agent. Many studies, referenced above, are exploring the combination of quercetin and other drugs as senolytic agents.

Quercetin is a flavanol that protects the eye from chronic solar radiation exposure. In addition, it may reduce inflammation, and is being investigated for use in helping reduce eye symptoms from allergens. It functions synergistically with vitamin E and taurine. Quercetin helps protect fine capillaries in the retina from deterioration and leaking. Both quercetin and rutin are important for a healthy macula, optic nerve health, and lens support.

• Glaucoma. Quercetin protects retinal ganglion cells in glaucoma models, independent of lowering intraocular pressure.¹⁰
• Macular degeneration. Quercetin is helpful through its antioxidant capacity to protect retinal pigment from oxidative stress that is caused by solar radiation. Quercetin also inhibits the formation of extra blood vessels, and improves blood flow in the choroid layer of the retina.¹¹
• Good Food Sources. Quercetin is highest in lingonberries. It is also found in dark red or blue fruit, such as cranberries and blueberries, as well as in black and green tea, capers, apples, red grapes, citrus, broccoli, and leafy-green vegetables. It is also in tomatoes.

Fisetin

Fisetin is a plant pigment and a flavonoid antioxidant with many benefits.¹² Studies have suggested that fisetin is effective against many diseases and reportedly has neurotrophic, anticarcinogenic, and anti-inflammatory effects.

Fisetin has been identified as a senolytic agent. One research team tested 10 nutrients: resveratrol, fisetin, luteolin, rutin, curcumin, epigallocatechin gallate, pirfenidone, myricetin, apigenin, catechin, and quercetin. They discovered that fisetin was the most effective in animal studies and human test tube tissue.¹³

• Dementia. Fisetin helps prevent oxidative stress-induced nerve cell death and may reduce the impact of Parkinson’s Disease, Alzheimer’s Disease, and dementia.¹⁴ It has been shown that fisetin can activate a signaling pathway that regulates gene expression and prevents apoptosis in nerve cells.¹⁵ Activation of this pathway is associated with fisetin’s neuroprotective, neurotrophic, and cognition-enhancing effects.
• Memory. Fisetin supports the hippocampus and enhances memory ¹⁶
• Cataracts. Animal studies show promise with fisetin ^{17 18}
• Macular degeneration. Fisetin, combined with luteolin, protects retinal pigmentary cells from oxidative damage.¹⁹
• Good food sources. This flavonoid is found in strawberries, apples, and persimmons. Fisetin occurs in lesser amounts in kiwi fruit, peaches, grapes, tomatoes, onions, and cucumbers.

Theaflavin

Theaflavin is a chemical that occurs naturally in black tea. It is also formed from green tea fermentation. Theaflavin is found as two antioxidant catechins: theaflavin-3-gallate and epigallocatechin-3-gallate. These catechins protect the brain, the cardiovascular system, and more.²⁰

• Dementia. These flavonoid catechins protect the aging brain, and reduce the incidence of dementia, Alzheimer’s, and Parkinson’s,²¹, reduce amyloid beta accumulation in mice,²² reduce cognitive decline, and improve working memory.²³
• Heart disease. Both forms of tea contain other active components which may contribute to reduced risk of cardiovascular disease,²⁴ cholesterol levels,²⁵ and hypertension.²⁶

Other Senolytic Drugs

Several drugs are being tested, both alone and in combination with nutrients like quercetin and fisetin.  These presently include navitoclax, 17-DMAG, piperlongumine, UBX-1325, and dasatinib. In particular, UBX-1325 holds promise for the treatment of diabetic retinopathy, diabetic macular edema, and advanced macular degeneration.²⁷

Other flavonoids with significant antisenescence effects include naringenin, hesperetin, hesperidin, kaempferol, rutin, apigenin, luteolin, nobiletin, tangeretin, genistein, wogonin, epigallocatechin gallate, theaflavin-3-gallate, and procyanidin C1.

A Healthy Lifestyle

What is most important to slowing the aging process is a healthy lifestyle.  A good diet with lots of fresh vegetables and fruits, a daily vigorous walk, protecting ourselves from stress, getting enough sleep. and for our vision — wearing UV-resistant sunglasses.

Supplements to Consider

Senolytic Activator 36 vegcaps – Contains a combination of quercetin, fisetin, and theaflavins.

Quercetin Bioflavonoids 100 vegcaps

Dr. Grossman’s Bilberry/Ginkgo Combination 2oz (60ml) – A wild-crafted, GMO-free tincture.

ReVision Formula (wild-crafted herbal formula) 2 oz – Based on a classic Liver tonic used in Chinese medicine supporting circulation and energy flow in the eyes as well as throughout the body

Dr. Grossman’s Blood Vessel Control Formula 2oz – helps reduce the risk of unwanted blood vessel growth (angiogenesis), helps reduce inflammation, improves blood flow, reduces oxidative damage, anxiety, and stress, supports brain health, and may improve collagen levels and bone strength.

Footnotes