Senescence and Senolytics

• “Beautiful young people are accidents of nature, but beautiful old people are works of art.”*

– Eleanor Roosevelt

When exploring therapeutics in longevity and regenerative medicine, we must discuss and understand senescence (a major hallmark of aging) and senolytics (agents that kill senescent cells).

As you learned in Chapter 15 of The Golden Gate book the accumulation of senescent cells (cells that are in cell cycle arrest but are not completely dead and instead continue to hang out) lead to inflammaging (chronic inflammation and aging). Senotherapeutics are agents that activate the cleanup of these senescent cells. Examples of senotherapeutics include senolytics (agents which kill senescent cells) and senomorphics (agents with modulate inflammaging).

Senescent cells form as a result of natural aging, DNA damage, chronic inflammation, radiation, UVB light, chemotherapy, and cancer. By using senotherapeutics to either activate the clean up or modulate senescent cells allows for a reduction in inflammaging thereby slowing aging while promoting longevity.

Below are lifestyle and dietary therapeutics as well as natural senotherapeutics that promote healthy aging and longevity through modulating or killing senescent cells and slowing their accumulation.

Lifestyle and Dietary Senotherapeutics

• Intermittent fasting

• Caloric restriction

• Mediterranean diet

• Healthy gut microbiome

• Adequate Sleep

• Exercise (15-60 min per day, 5 days per week)

Potential Natural Senotherapeutics

Potential natural senotherapeutics currently under study include (in no particular order):

• Rapamycin (found naturally in oyster mushrooms and shiitake mushrooms)

• Hesperidin

• Naringenin

• Fisetin (plant based polyphenol found in strawberries, onions, cucumbers, etc)

• Kaempferol (plant based polyphenol found in green leafy veggies and herbs like chives, dill, and tarragon)

• Quercetin (a polyphenol found in fruits and vegetables such as in yellow onions)

• Juglanin (from Polygonum aviculare)

• Rutin

• Apigenin (a bioflavonoid found in oranges, teas, onions, nuts, fruits and vegetables)

• Luteolin (from Lutein)

• Wogenin (from Scutellaria baicalensis Georgi)

• Genistein (from soy) – may mimic Rapamycin

• EGCG (green tea extract)

• Resveratrol

• Piperlongumine (from black pepper currently showing the most potential as to kill senescent cells.

• Curcumin (from turmeric spice)

• Astragalus

Each of you may resonate differently with each of the senolytics and senotherapeutics listed above. You may need one or two particular senolytics for a few weeks and then rotate them out so that your cells do not become resistant to the therapeutic benefits of these substances.

You may also find that you need assistance in identifying where to start or what to use to support you in your individual graceful longevity journey. Reach out to me or one of my colleagues at Holistique for a personalized and comprehensive therapeutic approach.

References:

Kim and Kim, “Senotherapeutics: emerging strategy for healthy aging and age-related disease” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386227/

Martel et al, “Lifestyle interventions to delay senescence”, May 2023 https://www.sciencedirect.com/science/article/pii/S2319417023001130?via%3Dihub

Mbara et al, “Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection”, Sept 2022 https://link.springer.com/article/10.1007/s40290-022-00444-w

Meiners et al, “Computational identification of natural senotherapeutic compounds that mimic dasatinib based on gene expression data” March 2024 https://citation-needed.springer.com/v2/references/10.1038/s41598-024-55870-4?format=refman&flavour=citation

Shetty et al, “Emerging Anti-Aging Strategies – Scientific Basis and Efficacy”, Dec 2018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6284760/