A HOLISTIC VIEW OF AGING
Pr Philippe Humbert and Dr Ferial Fanian
Aging is a complex phenomenon that not only depends on the passing of time but also our genetic heritage, lifestyle and the environment in which we live. Our skin suffers the effects of time in multiple ways. We are now paying more attention to the influence our diet has on how we age.
AGING, A LOSS OF FUNCTION
Until recently, we followed certain rules to slow down skin aging, and the medical profession made the definition of aging its own by describing it as the progressive loss of the functions in general and, more specifically, the cognitive, cardiovascular, muscular and, to a certain degree, digestive functions. To these functional issues, we might add a metabolic situation that deteriorates with age and excess weight: insulin resistance.
INSULIN RESISTANCE
We all know which illnesses and skin issues are most associated with insulin resistance. There is acanthosis nigricans, one of the signs of hyperinsulinemia. Acne is one of the signs of insulin resistance. Psoriasis is a metabolic disease in which the role of insulin resistance has now been proven, just like androgenetic alopecia, hirsutism, and Verneuil’s disease. Autoimmune alopecia and vitiligo also involve insulin resistance processes. Pathologies as common as skin tags and seborrheic keratosis should also be recognised as common signs of insulin resistance. (1, 2)
A WAY OF FIGHTING INSULIN RESISTANCE AND THEREFORE AGING
Physical activity, reducing calorie intake and eating high-quality foods all help to fight insulin resistance and therefore fight aging. Today, there are active ingredients that can help patients fight against this metabolic issue, which exposes them to cardiovascular problems (stroke, heart attack, etc.), metabolic issues (six times higher risk of type 2 diabetes) and cancer (insulin resistance is considered to be the primary cause of cancer): berberine in the field of naturopathy and metformin in pharmacopoeia.
METFORMIN
This medicine is used to treat type II diabetes, a form of glucose intolerance that occurs later on in life in people who are overweight or obese. Around 15 years ago, this medicine was shown to have a beneficial effect in non-diabetics (3) by regulating insulin production and therefore enabling them to lose weight. Since insulin resistance is, above all, an inadequate secretion of insulin, when there are no metabolic targets due to the absence of diabetes, it causes lipogenesis and therefore leads to obesity.
This medicine increases the person’s longevity, regardless of why it has been prescribed. (4) Metformin boasts several properties that make it a medicine to consider for the treatment of aging.(5-6)
Metformin’s cancer-fighting effects
We cannot separate aging from the risk of cancer. Metformin has a role to play in cancer prevention. Age, diabetes, a sedentary lifestyle and a poor diet are all risk factors for cancer, and they all have hyperinsulinemia, hyperglycaemia and inflammation in common. This observation has been confirmed for prostate cancer, breast cancer, pancreatic cancer and colon cancer.(7,8,9)
Neuronal degeneration
Alzheimer’s is a neurodegenerative disease that affects the cerebral tissue and leads to the gradual loss of mental functions, particularly the memory. Metformin pushes the neuronal stem cells to divide and could therefore stimulate the creation of new neurones.(10,11). We have seen that depression is a factor in aging. It has been shown that metformin could have an antidepressant effect, just like physical exercise.(12)
Mechanisms of action
Metformin reduces insulin resistance and does not lead to hypoglycaemia. Metformin reduces the hepatic production of glucose. In vivo, metformin primarily acts in the liver and skeletal muscle tissue by increasing insulin sensitivity in these organs.
Side effects (13)
• Digestive issues
The side effects mainly involve the digestive system. The main drawback of metformin is its relatively bad digestive tolerance (nausea, epigastric cramps, abdominal discomfort, diarrhoea).
• Lactic acidosis
Though it is rare, the worst complication, in the case of acute renal failure or hypoperfusion, is lactic acidosis.
It is a rare but serious metabolic complication that results in an accumulation of lactic acid. The rate of mortality from lactic acidosis can be up to 50%. The signs and symptoms include, in serious cases, nausea and vomiting, lethargy and polypnea. The risk of lactic acidosis increases when the patient’s renal dysfunction is more severe and when the patient is older.
It is important to warn patients taking metformin to avoid drinking excessive amounts of alcohol, to avoid potentiating lactate metabolism.
• Risk of vitamin B12 deficiency
Problems absorbing vitamin B12 were found in 10 to 30% of patients treated with metformin.
• Metformin and contrast agents
Patients must stop taking metformin before undergoing any radiological tests that require the injection of contrast agents.
Metformin prescription
In the absence of diabetes, metformin can only be prescribed off-label.
In addition to its neuro and cardio-protecting and anti-cancer properties, metformin promotes the loss of excess weight, which can be very important, or can help stabilise weight in obese patients.
Pr Philippe Humbert: Dermatologist specialising in internal medicine. He is particularly interested in integrative medicine, in which, in the face of dermatological symptoms, an organ-by-organ examination, a complete clinical examination (not just a skin examination), the taking into account of all blood samples taken prior to the consultation, and a selective choice of examinations to be carried out will enable the dermatosis to be linked to an internal problem.
More informations: philippehumbert.com
Dr Ferial Fanian: MD PhD. Dermatologist, Doctor of Life and Health Sciences Expert
in Aesthetic Dematology, Winner of the Awards for Medical Aesthetics in France 2022. She is a world reference in cutaneous biometrology. Member of the Board of the Imaging Group of the French Society of Dermatology. Scientific Director of Laboratoires FILLMED
Bibliography
1. Insulin resistance in aging is related to abdominal obesity. Kohrt WM, Kirwan JP, Staten MA, Bourey RE, King DS, Holloszy JO. Diabetes. 1993 Feb;42(2):273-81
2. The role of insulin-like growth factor in Acrochordon Etiopathology. Köseoğlu HG, Bozca BC, Başsorgun Cİ, Sarı R, Akbaş SH, Karakaş AA. BMC Dermatol. 2020 Nov 3;20(1):14.
3. Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Seifarth C, Schehler B, Schneider HJ. Exp Clin Endocrinol Diabetes. 2013 Jan;121(1):27-31
4. Metformin reduces all-cause mortality and diseases of ageing independent of its effect on diabetes control: A systematic review and meta-analysis. Campbell JM, Bellman SM, Stephenson MD, Lisy K. Ageing Res Rev. 2017 Nov;40:31-44
5. The protective effects of metformin in an in vitro model of aging 3T3 fibroblast under the high glucose conditions. Soydas T, Yaprak Sarac E, Cinar S, Dogan S, Solakoglu S, Tuncdemir M, Kanigur Sultuybek G. J Physiol Biochem. 2018 May;74(2):273-281
6. Metformin reverses the effects of high glucose on human dermal fibroblasts of aged skin via downregulating RELA/p65 expression. Soydas T, Sayitoglu M, Sarac EY, Cınar S, Solakoglu S, Tiryaki T, Sultuybek GK. J Physiol Biochem. 2021 Aug;77(3):443-450
7. Metformin – its potential anti-cancer and anti-aging effects. Podhorecka M, Ibanez B, Dmoszyńska A. Postepy Hig Med Dosw (Online). 2017 Mar 2;71(0):170-175
8. Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing. Hua Y, Zheng Y, Yao Y, Jia R, Ge S, Zhuang A. J Transl Med. 2023 Jun 21;21(1):403
9. Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis. Coyle C, Cafferty FH, Vale C, Langley RE. Ann Oncol. 2016 Dec;27(12):2184-2195
10. Metformin enhances endogenous neural stem cells proliferation, neuronal differentiation, and inhibits ferroptosis through activating AMPK pathway after spinal cord injury.
Xing C, Liu S, Wang L, Ma H, Zhou M, Zhong H, Zhu S, Wu Q, Ning G. J Transl Med. 2024 Aug 5;22(1):723
11. Metformin reduces neuronal damage and promotes neuroblast proliferation and differentiation in a cerebral ischemia/reperfusion rat model. Yuan R, Wang Y, Li Q, Zhen F, Li X, Lai Q, Hu P, Wang X, Zhu Y, Fan H, Yao R. Neuroreport. 2019 Feb 6;30(3):232-240
12. The role of metformin as a treatment for neuropsychiatric illness. Dodd S, Sominsky L, Siskind D, Bortolasci CC, Carvalho AF, Maes M, Walker AJ, Walder K, Yung AR, Williams LJ, Myles H, Watson T, Berk M. Eur Neuropsychopharmacol. 2022 Nov;64:32-43.
13. Side-effects of metformin.
Jackson WP, Coetzee EJ. S Afr Med J. 1979 Dec 22;56(26):1113-4
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