Longevity Research Roundup: HMGB1 | Thymosin Beta 4

HMGB1 propagates senescence, and Thymosin Beta 4 may help prevent Alzheimer's

The “Longevity Research Roundup” is a feature for paid subscribers of Longevity Lifehacks. Every week or two, I will bring you a quick summary of new research studies that I think are important — and actionable — in the fields of longevity, lifespan, or healthspan.

1) HMGB1 and Cellular Senescence

Study: Propagation of senescent phenotypes by extracellular HMGB1 is dependent on its redox state

Quick background: Cellular senescence is the ‘zombie’ state in which a cell is unable to divide due to damage or shortened telomeres. The senescent cell secretes pro-inflammatory factors, called the senescence-associated secretory phenotype (SASP), which signal for the immune system to clear them out. This process is normal and goes on throughout life. However, in aging, these senescent cells accumulate faster than they are cleared, leading to chronic low-level inflammation, dysfunction, and overall breakdown of systems in aging.

Once you have an excess of cellular senescence, the SASP (inflammatory signals) promotes nearby cells to become senescent or to function less optimally. Systemic propagation of senescence through the circulation of SASP factors in the bloodstream also drives the aging process.

HMGB1 is a protein that plays several roles in the cell. Typically, it is in the nucleus and helps with the arrangement of DNA so that it can be translated into a gene. However, when HMGB1 is released from a cell due to cell damage or trauma, it triggers an immune response as a damage-associated molecular pattern.

This new study shows that the reduced form of HMGB1 (reduced in the redox sense) is a driver of systemic transmission of senescence. The reduced form of HMGB1 (reHMGB1) is elevated in the bloodstream in people who are over age 70. Importantly, the animal portion of the study showed that blocking circulating HMGB1 with antibodies allows wounds to heal faster and reduces cellular senescence.

Natural inhibitors of HMGB1 secretion include:

• Fisetin[ref]

• Curcumin[ref][ref]

• Nicotine[ref]

• Vitamin B6 plus amino acids[ref]

You can read more about HMGB1 on Genetic Lifehacks.

---

2) Thymosin beta 4 peptide in Alzheimer’s