Stem Cell Therapy for Aging Frailty

What Is Aging?

Normal aging can be defined as the decline and deterioration of functional properties at the cellular, tissue and organ level. This loss of functional properties yields a loss of homeostasis and decreased adaptability to internal and external stress yielding an increased vulnerability to disease and mortality. 

Individuals are extremely heterogeneous in the onset of the aging process, rate at which it progresses, and extent to which it progresses. Differences in the manifestations of aging reflect differences in the functional capacity.

Functional capacity is a direct measure of the ability of our cells, tissues and organ systems to operate properly and is influenced by genes and environment. 

They are maintenance mechanisms that maintain homeostasis, including DNA repair, synthesis and fidelity surveillance, detection and clearance of defective proteins and lipids, clearance of defective organelles and cells, and defense against pathogens and injury. 

What is Frailty? 

Frailty is a geriatric syndrome characterized by weakness, weight loss and low activity that is associated with adverse health outcomes. Frailty manifests as an age-related, biological vulnerability to stressors and decreased physiological reserves yielding a limited capacity to maintain homeostasis. 

Frailty has been clinically defined as “a state of increased vulnerability resulting from aging-associated decline in reserve and function across multiple organ systems such that the ability to cope with everyday or acute stressors is compromised.”

Central to this geriatric medical syndrome is the notion that it has multiple causes and contributors that lead to the characteristic decreases in strength, endurance, activity, energy levels, and physiologic function, which increase the susceptibility to dependency and death. Although frailty is not characterized as a disability, it does increase the risk of disability in affected individuals. 

Patients also tend to show a greater risk of frailty when there are other comorbidities affecting their physical and psychological well-being, such as cardiovascular disease, diabetes, high blood pressure, cancer, or cognitive impairment. The main clinical presentations of frailty are falls, which are a result of impaired balance, gait, and awareness. Also other non-specific signs and symptoms, such as unexplained weight loss, infections and extreme fatigue.

Is Frailty a Normal Part of Aging? 

No. Frailty is not just a byproduct of aging. It is a standalone medical condition. The condition is sadly associated with a lower quality of life and a higher risk of death, hospitalization and institutionalization. 

While frailty is common among older adults, young people can become frail if they have one or mode disabling chronic diseases. 

One study that analyzed 46 studies of more than 120,000 people aged 60 and older living without assistance in 28 countries concluded that 4.3% of people in that age group develop frailty each year, and that women are more vulnerable than men.

Those findings suggest that the risk of developing frailty in older people is really high. This is a worldwide problem and highlights a major challenge facing countries with aging populations. More than 20% of the world’s population will be older than 60 by 2050, so the number of people with frailty is expected to rise.

“Inflammaging”

“Inflammaging” is a term that has been used to depict the particular molecular and cellular inter-related events that promote the process of aging. With aging, there is a continuous accumulation of damaged macromolecules and cells, generation of toxic metabolites and microbial byproducts, and development of cellular senescence and immunosenescence. 

Not only does inflammaging accelerate the aging process, it is linked with and accelerates the diseases associated with aging, including cardiovascular diseases, cognitive, and neurologic impairments, cancer, and degenerative joint disease. Importantly, the increased susceptibility to disease and death is a result of these molecular inflammation-related changes in physiological systems.

There is evidence that some inflammatory biomarkers such as TNF-α, interleukin-6 (IL-6), and C-reactive protein (CRP) increase during aging and that they can be independent predictors of mortality. This same inflammatory response underlies the tissue damage linked to various age-related chronic diseases. 

An individual’s endogenous stem cell production and function decreases with age and this decrease likely contributes to reduced ability to regenerate and repair organs and tissues. For instance, there is evidence that mesenchymal stem cells (MSCs) undergo senescence, their multilineage differentiation and homing capacity and immunomodulatory and wound healing properties gradually disappear. 

Use of Cellular Therapies for Aging Frailty

The use of mesenchymal stem cells for frailty therapy has been under study for a while. Some specific features of the frailty syndrome support a potential role of MSCs to ameliorate or improve frailty. MSCs are drawn to sites of injury, where they act to reduce inflammation and promote cellular repair. MSCs improve cardiovascular outcomes in patients with acute myocardial infarction, as well as ischemic and non-ischemic cardiomyopathy, reduce TNF-α and CRP levels, and are safe in patients irrespective of age. 

MSCs have effects in different frailty phenotypes such as: 

• Unintentional weight loss: they decrease chronic inflammation, onset of sarcopenia, and also decrease TNF-α, CRP and increase IL-10 and TFG-ß (which are anti-inflammatory cytokines).
• Low energy levels or exhaustion: they increase pulmonary function and decrease chronic inflammation. Increase endothelial function and decrease inflammatory biomarkers. 
• Weak grip strength: they can increase physical performance and endogenous stem cell function. 
• Slow gait speed: they can increase the 6 minute walk distance, increase endothelial function, cardiac performance and skeletal muscle performance.
• Low physical activity: they can decrease chronic inflammation and increase quality of life. 

MSCs can evade and modulate the host’s immune system to prolong their therapeutic effects without being detected and eliminated. The absence of major histocompatibility complex (MHC)/human leukocyte antigen (HLA) class II and associated costimulatory molecules and low levels of MHC/HLA class I molecules expressed by MSCs enables them to evade detection by the host immune system.

Currently there is no specific treatment approved for frail patients and therefore no established standard of care. The ultimate goal is to lengthen the healthy lifespan and restore or maintain cognitive and physical functionality of patients. Phase I studies using between 20 up to 200 million MSCs IV were reported to be well tolerated with no serious adverse events, indicating their safety, and patients had reductions of inflammatory biomarkers and increase in physical function. Several phase II trials are under development due to the good and promising results of phase I studies.

Stem Cell Treatment at Zignagenix 

In our clinic we offer stem cell therapy with Mesenchymal stem cells derived from the Warthon’s jelly umbilical cord, which have shown incredible results in multiple trials due to their ability of modulating the immune system and the inflammatory response in our bodies. 

As previously mentioned these studies have shown reductions of inflammatory markers, increased physical function and improved quality of life after the treatment with intravenously infused stem cells. We based our therapies in these studies to bring you the best available cellular therapies and for you to be able to increase your quality of life. 

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Sources: 

Schulman IH, Balkan W, Hare JM. Mesenchymal Stem Cell Therapy for Aging Frailty. Front Nutr. 2018;5:108. Published 2018 Nov 15. doi:10.3389/fnut.2018.00108

Fedarko NS. The biology of aging and frailty. Clin Geriatr Med. 2011;27(1):27-37. doi:10.1016/j.cger.2010.08.006.

Robert Preidt (2019, Aug 2) Frailty Not a Normal Part of Aging. WebMD. Retrieved from:
https://www.webmd.com/healthy-aging/news/20190802/frailty-not-a-normal-part-of-aging

Image from: 

https://stpsupport.nice.org.uk/frailty/index.html