The Anova IRM Stem Cell based Anti-Aging Program

Not classified as a disease, some experts would say aging is the ultimate of all diseases. It effects everyone and all will die from it. More though, the older we get, the more prevalent life threatening and crippling diseases become – directly or indirectly due to the effects of aging cells. Every systemic cellular anti-aging will therefore be worth its weight in gold later – prevention is always better than treatment. We use the medically and scientifically most advanced stem cells and senolytic based methods for cellular rejuvenation and anti-aging. Stem cells may not only be the solution to repair - and in the future even reverse - the effects of aging, but also improve the state of our organs. The Anova IRM Anti-Aging Program is a science based program that is as close as the world has ever been to a real cellular level anti-aging – and it is constantly improving.

The Maximum Lifetime of an Individual is Determined by Aging - What Exactly is Aging?

Aging is the set of morphological and physiological modifications that appear as a consequence of time. It leads to a reduction of the adaptive capacity of organs and systems as well as the responsiveness to harmful agents. It is a progressive biological process of most of the higher organisms that gradually leads to the loss of normal organ function and ends up with death. The maximum lifetime that an individual can reach is decisively determined by aging. Primary aging, also called physiological aging, is caused by cellular processes of aging which occur in the absence of diseases. It defines the “maximum attainable age” for an organism. Secondary aging, on the other hand, is the effect of external influences that shorten the maximum attainable age. Diseases, lack of exercise, defect symptoms or drug use for example can therefore influence the process of aging. Aging has many signs and affects some of our major body systems. It is not limited to the obvious effects on skin and hair – loss of efficiency of the heart muscle, thinning of the iris and lens, stiffing of joints and decease of neuronal connections are just a selection of effects. Furthermore, there are severe aging associated diseases such as cancer, Alzheimer`s disease, diabetes mellitus type 2, effort incontinence, myocardial infarction and osteoporosis.

Aging at The Cellular Level – Where It Begins and Where It Can be Stopped

At the cellular level, aging represents the progressive accumulation of sublethal lesions that can lead to cell death or at least a decrease in the cell's ability to respond to the lesion. Additionally, various cellular functions like the mitochondrial oxidative phosphorylation, nucleic acid synthesis, structural and enzymatic proteins, cellular receptors and transcription factors progressively deteriorate with increasing age. Aged cells have a reduced ability to collect nutrients and repair chromosomal lesions. At the same time, there is a progressive accumulation of the age pigment lipofuscin, a product of lipid peroxidation and protein oxidation and indicator for oxidative stress. The accumulation leads to a decreased cell function and tissues and organs will begin to deteriorate. Subsequently, if enough molecules are damaged, health will decline. Naturally, a cell can undergo a certain number of divisions before it enters a dormant state of cell cycle arrest called “senescence”. Senescence can be triggered by the telomere length, epigenetic clock and DNA damage. With increasing age, the number of senescent cells also increases. In that dormant state, the cells stop dividing and remain “silent” for many years bypassing apoptosis (programmed cell death). Senescent cells are not considered benign because they are one cause of aging, show oncogenic paracrine activities that stimulate cell proliferation and because they secrete cytokines, chemokines and proteases (senescence associated secretory phenotype, SASP). These accumulated proteases promote chronic tissue inflammation and tissue deterioration (please click here if you want to know more about senescence).

Current Treatment Methods for Anti-Aging – an Overview

Easy and traditional methods use natural oils, anti-oxidants, special diet programs, vitamins, alpha hydroxyl acids, hormones, petroleum-based products (in beauty creams) or sulfates to treat aging skin. Conventional anti-aging treatments are offered by innumerable practitioners worldwide. Often, they include microdermabrasion, chemical peeling, botox injections, fillers, laser surfacing, latisse and sclerotherapy. Sclerotherapy uses saline injections to eliminate unsightly large veins that are close to the skin’s surface, veins may turn into scar tissue that fades. Latisse is a treatment using bimatoprost to stimulate hair growth at the root. Known side effects are burning of the eyes and darkening of the iris. The effects of fillers (wrinkle or dermal fillers like collagen and hyaluronic acid are used to fill in lines and help lifting certain areas), botox injections (toxins reducing/erasing wrinkles by blocking muscle contractions), chemical peeling (chemical destruction of uppermost skin layer revealing a new one underneath) and microdermabrasion (skin smoothing and texture refinement by physically removing dry skin) only have a temporary effect on the skin as their results only last a limited time. Also, their anti-aging effects never go beyond the treated areas.

Potential treatment methods for anti-aging reach from conventional anti-aging treatments to the approach of removing senescent cells or bypassing senescence. To recap, senescence is a dormant state of cell cycle arrest. The number of senescent cells increase with age and they secrete cytokines, chemokines and proteases (senescence associated secretory phenotype, SASP). Senoyltics are a new class of drugs used to remove senescent cells. They can extend lifespan and reduce age related symptoms. Glucocorticoids can repress SASP-induced inflammations from senescent cells but there are side effects and drug resistances (Soto-Gamez & Demaria, 2017). Metformin, an antidiabetic drug, shows an inhibitory effect on SASP and reduces oxidative stress ((Moiseeva et al., 2013; Martin-Montalvo et al., 2013). Phenols and flavonoids can also reduce oxidative stress (Pitozzi et al., 2013; Lim et al., 2015). Rapamycin can suppress SASP components that hold the arrested cell in senescence associated growth arrest (Soto-Gamez & Demaria, 2017). Also, by using JAK inhibitors, it was possible to enhance the efficacy of chemotherapy and achieve positive effects on age-related symptoms (Toso et al., 2015; Xu et al., 2015). Statins, lipid-lowering drugs, also showed to reduce the expression of pro-inflammatory SASP proteins due to protein prenylation (Liou et al., 2014). Another approach to reduce age related effects of the SASP is the use of monoclonal antibodies directed against SASP proteins (Mian et al., 2003; Karkera et al., 2011). Senolytic drugs like quercetin and dasatinib are also able to reduce age-related symptoms but showed only selective removal of senescent cells from different tissues (Soto-Gamez & Demaria, 2017). Unfortunately, there are many possible side effects and open questions regarding the removal or reprogramming of senescent cells that must be taken into consideration. Overcoming of growth arrest in cells with DNA damage or oncogenic activation may result in hyperplastic anomalies. Considering this, removal of senescent cells should be preferred instead of bypassing senescence (Soto-Gamez & Demaria, 2017). As senescent cells facilitate wound healing by reducing fibrosis and attracting immune cells, a delay in wound healing could be a possible outcome of senescent cell removal (Sagiv et al., 2013; Demaria et al., 2014).

Stem Cell Treatment For Anti-Aging Effects

As seen above, Aging can be treated with various mechanisms. This approach to Anti-Aging underlies a different method. Current studies show a protective effect of adipose-derived stem cells (ADSCs) for human dermal fibroblasts to prevent skin damage from free radicals, which is one of the factors of the aging process. The effects of the stem cells are not limited to anti-oxidation, but also include immuno-modulation effects which can reduce the aging process by moderation of the cytokine production. In the past, many medical treatments have been used to treat the symptoms of photo-aging, though without satisfying results. ADSCs secrete various growth factors which can both control and repair damaged skin cells. There is evidence that conditioned medium from ADSCs (short ADSC-CM), which contain stem cell secretome can stimulate collagen synthesis and migration of dermal fibroblasts, both of which can reduce skin-aging and quicken wound healing processes.

But the anti-aging effects of stem cells are not limited to the skin. Stem cells and their secretome have been shown to have a regenerative effect on many organs and functional systems in the body:

  • Regeneration of impaired function of the kidneys and liver
  • Improved endo- and exocrine function of the pancreas
  • Reduction of insulin-tolerance in diabetes
  • Improved cognitive function
  • Increased production of sexual and growth hormones

Anova IRM Stem Cell Based Treatment Strategies for Aging

Stem cell based treatment strategies range from the direct application of mesenchymal stem cells (isolated from adipose tissue (ADSCs) or bone marrow) to mesenchymal stem cell conditioned medium (ADSC-CM ) that contains the stem cell secretome. Aging is by far the most important risk factor for diseases such as cancer, coronary heart disease, Alzheimer's disease, Parkinson's disease and chronic renal failure. ANOVA delivers the beneficial effects of secretome gained from mesenchymal stem cells (MSCs) in anti-aging, tailored to your specific needs, without the uncertainty and risk of treatments outside regulated medical systems. All stem cell procedures are in accordance with the strict quality standards of Germany and the respective healthcare regulations of the country where the treatment is administered.

At ANOVA, we are not restricted to the secretome from stem cells. They are simply the latest addition to an increasingly effective medical treatment form to slow down and eventually reverse the effects of aging. To find out what is best for you, our specialists will subject you to a detailed check-up of your whole body before deciding on the specifics of the anti-aging treatment. The check-up team will help you to obtain a general idea of your body’s current status by comprising the following components:

  • In depth medical history
  • General physical exam
  • Personalized clinical chemistry (blood and urine)
  • Cardio-vascular check-up including EKG, Echocardiography, Cardio-CT and/or MRI, etc.
  • Cancer check with tumor markers, whole-body MRI, (virtual) colonoscopy, low-dose CT of the lungs (smoker), MR-mammography, etc.

Additional anti-aging measurements may include but are not limited to:

  • Hormone optimization
  • Metabolic and body composition optimization
  • Anti-oxidation treatment
  • Dietary optimization
  • Personalized exercise program
  • NAD+ precursors
  • Quercitin
  • Dasatinib
  • Navitoclax
  • Stem Cell Secretome
  • Autologous Growth facts i.e. from platelet rich plasma (PRP) concentrations
  • Targeted use of HGH

If you have any questions regarding our anti-aging treatment at ANOVA Institute for Regenerative Medicine, simply give us a call or contact us by e-mail. Contact us for more information, or make an appointment right away. Our specialists will be happy to advise you on the best therapy.

References and Literature - Stem Cell-based Therapies and Anti-Aging (Click for more)

Park, Byung-Soon, and Won-Serk Kim. "Adipose-Derived Stem Cells and Their Secretory Factors for Skin Aging and Hair Loss." Textbook of Aging Skin (2017): 205-224.

Xu, Dan, and Hidetoshi Tahara. "The role of exosomes and microRNAs in senescence and aging." Advanced drug delivery reviews 65.3 (2013): 368-375.

Prattichizzo, Francesco, et al. "Exosome-based immunomodulation during aging: a nano-perspective on inflamm-aging." Mechanisms of Ageing and Development (2017).

Basu, Joydeep, and John W. Ludlow. "Exosomes for repair, regeneration and rejuvenation." Expert opinion on biological therapy 16.4 (2016): 489-506.

Park, Byung-Soon, and Won-Serk Kim. "Adipose-derived stem cells and their secretory factors for skin aging." Textbook of Aging Skin. Springer Berlin Heidelberg, 2010. 201-212.

Soto-Gamez, A., & Demaria, M. (2017). Therapeutic interventions for aging: the case of cellular senescence. Drug Discovery Today.

Moiseeva, O. et al. (2013) Metformin inhibits the senescence-associated secretory phenotype by interfering with IKK/NF-kB activation. Aging Cell 12, 489–498.

Martin-Montalvo, A. et al. (2013) Metformin improves healthspan and lifespan in mice. Nat. Commun. 4, 2192.

Pitozzi, V. et al. (2013) Chronic resveratrol treatment ameliorates cell adhesion and mitigates the inflammatory phenotype in senescent human fibroblasts. J. Gerontol. A Biol. Sci. Med. Sci. 68, 371–381.

Lim, H. et al. (2015) Effects of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts. Biochem. Pharmacol. 96, 337–348.

Toso, A. et al. (2015) Enhancing chemotherapy efficacy by reprogramming the senescence-associated secretory phenotype of prostate tumors: a way to reactivate the antitumor immunity. Oncoimmunology 4, e994380.

Xu, M. et al. (2015) Targeting senescent cells enhances adipogenesis and metabolic function in old age. eLife 4, e12997.

Liou, C.J. et al. (2014) Oral lovastatin attenuates airway inflammation and mucus secretion in ovalbumin-induced murine model of asthma. Allergy Asthma Immunol. Res. 6, 548–557.

Mian, B.M. et al. (2003) Fully human anti-interleukin 8 antibody inhibits tumor growth in orthotopic bladder cancer xenografts via down-regulation of matrix metalloproteases and nuclear factor-kappaB. Clin. Cancer Res. 9, 3167–3175.

Karkera, J. et al. (2011) The anti-interleukin-6 antibody siltuximab down-regulates genes implicated in tumorigenesis in prostate cancer patients from a Phase I study. Prostate 71, 1455–1465.

Pellegrini, G. et al. (2004) Telomerase activity is sufficient to bypass replicative senescence in human limbal and conjunctival but not corneal keratinocytes. Eur. J. Cell Biol. 83, 691–700.

Abad, M. et al. (2013) Reprogramming in vivo produces teratomas and iPS cells with totipotency features. Nature 502, 340–345.

Sagiv, A. et al. (2013) Granule exocytosis mediates immune surveillance of senescent cells. Oncogene 32, 1971–1977.

Demaria, M. et al. (2014) An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31, 722–733.

Pei, Ming. "Environmental preconditioning rejuvenates adult stem cells' proliferation and chondrogenic potential." Biomaterials (2016).

Vañó-Galván, S., and F. Camacho. "New Treatments for Hair Loss." Actas Dermo-Sifiliográficas (English Edition) (2017).

Anitua, Eduardo, Ander Pino, and Gorka Orive. "Opening new horizons in regenerative dermatology using platelet‐based autologous therapies." International journal of dermatology 56.3 (2017): 247-251.

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