Ageing, chronic inflammation and stem cells — what randomised frailty trials measured

Summary — With age, low-grade inflammation often persists in the body even without obvious infection or disease, a phenomenon called 'inflammageing'. It is known to be linked to loss of strength and to frailty. A University of Miami team carried out a phase I study and a randomised, double-blind phase II study (2017) giving intravenous mesenchymal stem cells, which modulate inflammation, to frail older adults, and reported improved six-minute walk distance and reduced blood inflammatory markers in one dose group. This article covers the background, what was measured and the scope of the results.

What is inflammageing?

In youth, inflammation is a defensive response that arises briefly against infection or injury and then subsides. With age, however, the accumulation of damaged cells, changes in the immune system, increased fat tissue and changes in the gut environment often leave blood levels of inflammatory substances (interleukin-6, TNF-α, C-reactive protein and others) persistently raised at a low level. Many studies have linked this chronic inflammation to muscle loss, reduced mobility, cardiovascular disease and cognitive decline. Ageing itself cannot be stopped, but research is exploring whether controlling this inflammation might slow age-related decline in function.

Frailty and inflammation

Frailty is a state in which strength, walking speed, activity, weight and vitality decline together so that health collapses easily under minor stress. Frail older adults have been reported to tend to have higher blood inflammatory markers than non-frail peers. Researchers therefore hypothesised that reducing inflammation might slow frailty or improve physical function. Mesenchymal stem cells, which secrete factors that modulate immune responses and inflammation, were chosen as a candidate to test this hypothesis.

Phase I: confirming safety (2017)

The University of Miami team gave a single intravenous infusion of allogeneic mesenchymal stem cells from young donors to 15 older adults meeting frailty criteria. The main aim was safety, and no serious infusion-related adverse events were reported. Improvements in six-minute walk distance, physical function measures and blood inflammatory markers such as TNF-α were observed after infusion. Because every participant received cells in this open-label study, a further study was needed to confirm these changes.

Phase II: randomised, double-blind and placebo-controlled (2017)

In phase II, 30 frail older adults were randomised to 100 million cells, 200 million cells or placebo, with neither participants nor assessors knowing who received what. At six months, six-minute walk distance improved significantly more in the 100-million group than with placebo, and blood TNF-α levels fell. Interestingly, the same degree of difference was not seen in the 200-million group, which received more cells — suggesting that the relationship is not simply 'more cells, more effect' and leaving the right dose as an important question. Both studies were published in a gerontology journal.

Scope of the results: what was and was not measured

These studies measured specific outcomes: six-minute walk distance, physical function scores and blood inflammatory markers. They did not measure whether life is extended, skin looks younger or ageing itself is reversed. With only 30 participants and six months of follow-up, it is not yet known whether the results hold at the same size in more people or how long any effect lasts. The ISSCR warns about 'anti-ageing' stem cell interventions sold without evidence, and the U.S. FDA also urges caution about unapproved stem cell interventions.

In short

Inflammageing is an important framework for understanding frailty, and the University of Miami research is significant for testing stem cell administration aimed at it in a randomised, double-blind design. At the same time, established basics of frailty management such as exercise and nutrition remain important. See the 'Frailty & Ageing' page for details.

Frequently asked questions

Q. Does lowering inflammation slow ageing?
Many studies link chronic inflammation with frailty, but it has not been shown in people that lowering inflammation slows ageing itself. The University of Miami studies measured walking distance and inflammatory markers over six months; they did not measure the rate of ageing.

Q. Do more cells mean a bigger effect?
In the phase 2 study, a difference was reported in the 100-million-cell group but not to the same degree in the 200-million group. The relationship between dose and effect has not yet been worked out.

Q. What are the basics of managing frailty?
Strength and balance exercise, adequate protein and nutrition, and social participation are the foundations of frailty management, with benefits reported in many studies. In Japan, local governments run frailty check-ups and exercise and nutrition programmes.

How to look up clinical trial information

Ongoing and completed clinical trials can be checked on public registries. ClinicalTrials.gov, run by the U.S. National Library of Medicine, and jRCT, run by Japan's Ministry of Health, Labour and Welfare, publish each study's purpose, eligibility criteria, intervention, outcomes, institutions and status. Results are later published as journal papers, and the reference links below this article lead to the original information. It is also worth knowing that interventions not publicly registered are difficult to verify from outside, in both design and results.

The above summarises results reported in published papers and public-agency materials. University and institute names are given to identify research sources, not to introduce or recommend any medical institution. The suitability of any treatment is decided by the medical team.

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