Immune function
Function of the immune system, especially vaccine response; improved by low-dose everolimus in older adults.
How well the immune system works.
Rapalogs are immunosuppressants at transplant doses, yet low-dose everolimus improved influenza vaccine responses in the elderly (Mannick 2014/2018) – dose and schedule determine the direction.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| S | Synthesis of human data | 1 |
| H | Human study | 4 |
Studies
| Year | Evidence | Study |
|---|---|---|
| 2024 | S | Targeting ageing with rapamycin and its derivatives in humans: a systematic review LEE2024 The first systematic review of rapamycin/rapalogs in humans for aging. Screened 18,400 articles, included 19 studies. Found improvements in immune, cardiovascular, and skin (integumentary) parameters; NO significant effect on endocrine, muscular, or neurological systems. No serious adverse events in healthy people, but more infections and raised cholesterol/triglycerides in people with age-related disease. This is the highest-tier human-evidence summary in the whole Atlas - it aggregates many individual human studies rather than reporting one. |
| 2021 | H | Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials MAN2021 The crucial reality check. After the promising phase 2a, the large phase 3 trial (n=1024) FAILED its primary endpoint - RTB101 did not reduce clinically symptomatic respiratory illness (26% vs 25%, p=0.65). It still reliably switched on antiviral genes, so the biomarker moved but the clinical outcome did not. A textbook lesson that a promising biomarker is not a proven benefit. |
| 2018 | H | TORC1 inhibition enhances immune function and reduces infections in the elderly MAN2018 The strongest human evidence that mTOR inhibition can rejuvenate a specific function of aging - immunity. In 264 elderly people, a low-dose combination that selectively hits TORC1 significantly reduced infections over the following year and boosted antiviral gene expression and flu-vaccine response. The follow-up to Mannick 2014. |
| 2018 | H | A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort KRA2018 A safety-first pilot RCT (n=25, ages 70-95) asking the basic question before any longevity trial: is daily rapamycin safe in healthy older people? Over 8+ weeks it was well tolerated with only minor red-blood-cell changes and - importantly - NO rise in blood glucose or insulin resistance in this short window. Groundwork for larger aging trials like PEARL. |
| 2014 | H | mTOR inhibition improves immune function in the elderly MAN2014 Low-dose everolimus improved influenza vaccine response by ~20% and reduced PD-1 expression on T lymphocytes. |