Review: Dr. Alejandro Ramírez Restrepo, Medical Director at Lumm
Latest evidence review: August 2026
In a nutshell
Frailty is a syndrome associated with a reduced ability of the body to respond to and recover from situations such as an infection, surgery, a fall, or a period of inactivity.
It is not an inevitable consequence of aging.
Exercise, especially when it combines strength, aerobic activity, and balance, is one of the most supported interventions to preserve mobility and independence. At the same time, mesenchymal stem cells (MSCs) have growing clinical evidence: various trials have shown a favorable safety profile and improvements in physical capacity, strength, quality of life, and certain inflammation-related markers.
What is frailty?
Frailty is a state of physiological vulnerability in which the body’s reserve and its ability to respond to a stressor are diminished.
One of the most widely used definitions is Fried’s frailty phenotype, which considers five criteria:
- Unintentional weight loss;
- exhaustion;
- decreased muscle strength;
- slow walking speed;
- low physical activity.
The presence of three or more criteria corresponds to the classic fragility phenotype [1].
Frailty is not the same as sarcopenia, although the two are closely related. Sarcopenia refers primarily to the loss of muscle strength and mass, while frailty reflects a broader vulnerability that can involve various body systems.
Why is it important to detect it?
Frailty has been linked to an increased risk of:
- falls;
- hospitalization;
- disability;
- loss of independence;
- mortality.
That is why, when it comes to healthy aging, knowing one’s chronological age is not enough. It is also important to assess variables such as strength, walking speed, balance, body composition, and cardiorespiratory fitness.
Exercise: The Foundation of Frailty Management
The evidence on physical activity is strong.
The LIFE study, which included more than 1,600 older adults, showed that a structured exercise program reduced the onset of major mobility impairment compared to health education [2].
Subsequent systematic reviews and meta-analyses have confirmed that multicomponent programs—combining strength, aerobic activity, and balance—can improve mobility, physical performance, and frailty status [3,4].
For this reason, maintaining muscle strength and mobility remains a central component of any strategy for healthy aging.
MSC and Frailty: Increasingly Consistent Clinical Evidence
Mesenchymal stem cells have taken on an increasingly important role in frailty research due to their immunomodulatory, anti-inflammatory, and trophic properties.
Its appeal is not based solely on biological mechanisms. Clinical trials are already underway in people with age-related frailty.
Early studies using allogeneic MSCs administered intravenously showed good tolerability and signs of benefit in variables such as:
- a six-minute walk;
- physical performance;
- quality of life;
- TNF-α and other inflammatory markers.
[5,6]
These results were significant because they showed that cell therapy could produce measurable changes not only in biomarkers but also in physical function.
Zhu 2024: Umbilical Cord MSCs and Functional Outcomes
In 2024, a randomized, double-blind, placebo-controlled Phase I/II trial was published that evaluated umbilical cord tissue-derived MSCs in 30 adults aged 60 to 80 with frailty or pre-frailty. The participants received two intravenous infusions of HUC-MSCs or a placebo.
At six months, the treatment group showed favorable results compared with the placebo group on several clinically relevant variables:
- improvement in the physical component of the SF-36;
- better performance on the Timed Up and Go test;
- a four-meter improvement in walking distance;
- greater gripping force;
- better overall perception of health as measured by the EQ-VAS;
- reduction in TNF-α and IL-17.
No serious treatment-related adverse events were observed.
These findings are significant because they combine functional improvement with modulation of inflammation, two key aspects of frailty syndrome.
What is the relationship between MSCs and muscle?
Research on sarcopenia provides a complementary biological basis.
A review by Wong and Cheong describes several potentially relevant mechanisms of MSCs in muscle health:
- modulation of inflammation;
- reduction in apoptosis;
- interaction with satellite cells;
- regulation of the cellular microenvironment;
- support for skeletal muscle homeostasis.
The same review includes preclinical studies using MSCs derived from Wharton’s jelly, in which improvements were observed in strength, endurance, muscle mass, and satellite cell proliferation, as well as a reduction in pro-inflammatory cytokines.
Although these preclinical results should not be directly extrapolated to demonstrate efficacy in humans, they do provide biological consistency with the functional findings observed in clinical studies of frailty.
The Phase 2b trial in 2026
In 2026, a Phase 2b trial involving 148 participants significantly expanded the available evidence.
The study evaluated laromestrocel, a therapy based on allogeneic bone marrow-derived MSCs.
One of its most notable findings was a difference of:
63.4 meters in the six-minute walk test compared with placebo at nine months
with a 95% confidence interval of 17.1 to 109.6 meters and a p-value of 0.0077 [7].
This study reinforces the clinical findings observed in previous trials and represents a significant advance in terms of sample size and the strength of the evidence.
What does the current evidence show?
| Intervention | Current State of the Evidence |
|---|---|
| Multicomponent Exercise | Consolidated evidence |
| Proper Nutrition | Important, especially in cases of sarcopenia or malnutrition |
| MSC | Promising and growing clinical evidence |
| MSC and Physical Capacity | Repeated positive results in various trials |
| MSC and Inflammation | Consistent results for some biomarkers |
| Very Long-Term Results | Still under investigation |
Further research is needed to determine more precisely the optimal dose, the ideal number of treatments, which patients are likely to benefit the most, and how long the effects last.
However, the available data suggest that MSCs can be considered a relevant strategy in the clinical management and research of age-related frailty.
Exercise and MSC: More Complementary Than Mutually Exclusive
Exercise directly affects strength, cardiovascular fitness, balance, and muscle adaptation.
MSCs can act on various mechanisms, including inflammation, immune regulation, paracrine signaling, and the tissue microenvironment.
Therefore, the most interesting approach is not necessarily to present a choice between the two, but rather to evaluate how they can be part of a comprehensive and individualized management plan.
What Can a Person Do Today?
The most important measures include:
- do strength training on a regular basis;
- engage in aerobic activity;
- work on balance;
- maintain proper nutrition;
- monitor for loss of strength or walking speed;
- periodically assess functional capacity.
When functional decline or a risk of frailty is already present, a medical evaluation can help determine whether, in addition to these measures, it makes sense to consider regenerative medicine interventions.
Lumm’s Perspective
At Lumm, we view longevity not only as living longer, but also as preserving—for as long as possible—mobility, strength, independence, and resilience.
That is why our approach begins with measuring before taking action.
Programs such as LummAge make it possible to integrate biological markers with functional variables—such as grip strength, body composition, and cardiorespiratory fitness—to establish a baseline and guide future decisions.
In regenerative medicine, we follow the same principle: measure → understand → intervene → measure again.
When cell therapy may be appropriate in a patient’s clinical context, the decision should take into account the patient’s medical history, functional status, goals, potential benefits, risks, alternatives, and expectations.
Frequently Asked Questions
Is frailty inevitable as we age?
No. Its prevalence increases with age, but people of the same age may have very different functional abilities.
Can frailty be improved?
Yes. Strength, mobility, balance, and physical performance can improve, especially when intervention begins early.
Can MSCs improve physical function?
Various clinical trials have reported improvements in walking ability, strength, physical performance, and quality of life, although the extent of the benefit may vary depending on the patient and the protocol used.
Do MSCs replace exercise?
No. Current evidence supports a complementary approach, not a substitute one.
Conclusion
Frailty should not be viewed as an inevitable consequence of aging.
Multicomponent exercise remains a key intervention for maintaining strength, mobility, and independence.
At the same time, the evidence regarding mesenchymal stem cells has evolved significantly. Various clinical trials have demonstrated a favorable safety profile and signs of benefit in physical function, strength, quality of life, and inflammation.
Research on sarcopenia also provides a biological basis consistent with these findings, particularly due to the immunomodulatory, anti-inflammatory, and muscle homeostasis-related effects of MSCs.
Based on the evidence currently available, MSCs represent one of the most promising strategies in regenerative medicine as applied to functional aging, especially when integrated into an individualized medical evaluation.
Medical Notice
This content is for educational purposes only and is not a substitute for an individual medical evaluation. Recommendations regarding exercise, nutrition, rehabilitation, or cell therapy should be tailored to each patient’s medical history, functional status, risks, and goals.
References
- Fried LP, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56(3):M146-M157.
- Pahor M, et al. Effect of structured physical activity on the prevention of major mobility disability in older adults: the LIFE Study randomized clinical trial. JAMA. 2014;311(23):2387-2396.
- Valenzuela PL, et al. Effects of physical exercise on physical function in older adults in residential care. Lancet Healthy Longev. 2023;4(6):e247-e256.
- Yang X, et al. Effects of multicomponent exercise on frailty status and physical function in frail older adults. Exp Gerontol. 2024;197:112604.
- Golpanian S, et al. Allogeneic human mesenchymal stem cell infusions for aging and frailty. J Gerontol A Biol Sci Med Sci. 2017;72(11):1505-1512.
- Tompkins BA, et al. Allogeneic mesenchymal stem cells alleviate age-related frailty: a phase II randomized, double-blind, placebo-controlled clinical trial. J Gerontol A Biol Sci Med Sci. 2017;72(11):1513-1522.
- Ruiz JG, et al. Randomized Phase 2b Dose-Escalation Trial of Stem Cell Therapy with Laromestrocel for Aging-Related Frailty. Cell Stem Cell. 2026;33(3):393-404.e4.
- Zhu Y, et al. Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with age-related frailty: a phase I/II randomized, double-blind, placebo-controlled study. Stem Cell Res Ther. 2024;15:122.
- Wong RSY, Cheong SK. Therapeutic potential of mesenchymal stem cells and their derivatives in sarcopenia. Malays J Pathol. 2022;44(3):429-442.
