He described his work as identifying and promoting specific technological approaches to the reversal of various aspects of aging, or, as he puts it, "... the set of accumulated side effects from metabolism that eventually kills us.

"[20] As of 2005[update], de Grey's work centered on a detailed plan called strategies for engineered negligible senescence (SENS), which is aimed at preventing age-related physical and cognitive decline.

The foundation "works to develop, promote and ensure widespread access to regenerative medicine solutions to the disabilities and diseases of aging",[21] focusing on the strategies for engineered negligible senescence.

De Grey stated in March 2005 "if we are to bring about real regenerative therapies that will benefit not just future generations, but those of us who are alive today, we must encourage scientists to work on the problem of aging."

[25] In 2022, de Grey started the Longevity Escape Velocity Foundation, which funded and launched a project focusing on robust mouse rejuvenation.

[29][30][31] De Grey was formerly Vice President of New Technology Discovery at AgeX Therapeutics, a startup in the longevity space helmed by Michael D. West.

[32][33][34] Xenocatabolism is a concept in medical bioremediation that relies upon introducing into the body microbial enzymes that break down pathogenic lysosomal, cytosolic and extracellular aggregates.

[citation needed] De Grey believes that medical technology may enable human beings alive today not to die from age-related causes.

According to de Grey, that is synonymous with the point where science achieves longevity escape velocity–the minimum rate at which those therapies need to be improved in order to allow people not to suffer from age-related ill-health at any age.

[40] However, de Grey views the fatalistic attitude toward aging in society, as he sees it, as a hurdle in the rapid development of anti-aging medicine, which he calls "pro-aging trance".

[41] In 2005, MIT Technology Review, in cooperation with the Methuselah Foundation, announced a US$20,000 prize for any molecular biologist who could demonstrate that SENS was "so wrong that it is unworthy of learned debate."

The judges concluded that none of the challengers had disproved SENS, but the magazine opined that Preston Estep's submission was particularly eloquent and well written, and awarded the contestant US$10,000.

[44] A 2005 article about SENS published in the viewpoint section of EMBO Reports by 28 scientists concluded that none of de Grey's hypotheses "have ever been shown to extend the lifespan of any organism, let alone humans".

[45] The SENS Research Foundation, of which de Grey was a co-founder, acknowledged this, stating, "If you want to reverse the damage of aging right now I'm afraid the simple answer is, you can't.

"[53] In August 2021, following allegations of sexual harassment by two women, de Grey was put on administrative leave by the SENS Research Foundation (SRF).

[55]The SRF board of directors decided to remove de Grey from his position as chief science officer, severing all ties with him following the report that he had allegedly attempted to interfere with the investigation.