Dr Mayoni Gooneratne explores why cell optimisation enhances outcomes when treating the ageing face.
Facial ageing is an intricate process influenced by a myriad of factors, both internal and external.1 As we age, the face undergoes significant morphological changes affecting various tissue layers, including bone structure, muscle mass, fat distribution, and skin quality.1
To effectively address the multifaceted nature of facial ageing, a comprehensive strategy focusing on cell optimisation before treating the end organ, namely the skin and facial structures, is paramount.
What we have been taught and what we tell our patients needs to be much more holistic than it is. But what has become clear to me while writing this article is the lack of evidence around the importance of cell optimisation as part of that holistic approach.
This month, I will explore the topic as it pertains to the ageing of the deep structures, including bone, fat, and muscle. Next month, I will delve deeper into cell optimisation for treating the skin.
The ageing process: Internal and external factors
· Intrinsic factors
Intrinsic ageing stems from genetic predispositions and biological processes inherent to ageing. Factors such as hormonal changes, particularly the decrease in oestrogen levels during menopause, contribute to reduced collagen production and skin thickness. Additionally, cellular damage accumulates over time, leading to decreased turnover and functionality of cells crucial for maintaining skin health.
WOULD THERE BE A POSSIBILITY TO RECREATE THIS DIAGRAM?
The 12 hallmarks of ageing2 are:
1. Genomic instability
2. Telomere attrition
3. Epigenetic alterations
4. Loss of proteostasis
5. Disabled macroautophagy
6. Deregulated nutrient-sensing
7. Mitochondrial dysfunction
8. Cellular senescence
9. Stem cell exhaustion
10. Altered intercellular communication
11. Chronic inflammation
12. Dysbiosis
These hallmarks are interconnected among each other, as well as to the recently proposed hallmarks of health3, which include organisational features of spatial compartmentalisation, maintenance of homeostasis, and adequate responses to stress.
· Extrinsic factors
External factors, such as sun exposure, lifestyle choices, and environmental pollutants, accelerate skin ageing. Ultraviolet (UV) rays from the sun, especially UVA and UVB, induce collagen and elastin degradation, resulting in wrinkles, sagging, and uneven pigmentation. Lifestyle habits like smoking and excessive alcohol consumption further exacerbate skin damage by impeding blood flow and impairing the skin's ability to repair itself.
There are also digital toxins, such as blue light from devices, toxins from plastics, pesticides and chemicals sprayed onto our food. And sugar, which plays a major role in glycation (a topic we will explore further in next month’s article).4
The interaction between intrinsic and extrinsic ageing is what we see in aesthetics. We can either work at a cellular level and address ageing from an internal longevity perspective or focus on the extrinsic. But I believe we have a duty of care to ask about our patient's lifestyles. If you do not, you are not working holistically.
Mechanisms of facial ageing
There are two main types of mechanisms that play a role in facial ageing: tissue modification involving all components of the face and a global drop of the facial tissues. This topic is well reported and so I am not going to focus on it in this in this article.
· Tissue modification:
Facial ageing involves alterations in all components of the face, including the skin, muscles, fat pads, and bone structure. Skin elasticity diminishes, leading to fine lines, wrinkles, and sagging. Muscles experience hypotony, contributing to visible slackening, particularly around the lips and eyes. Fat distribution changes, with some areas experiencing volume loss while others exhibit progressive decline.
· Global drop of facial tissues:
The structural integrity of facial tissues, including the superficial musculoaponeurotic system (SMAS) and bony scaffolding, undergoes significant changes with age under the influence of gravity. Muscular ageing involves a reduction in muscle mass and metabolism, exacerbating facial sagging. Fatty tissue may decrease in certain regions, while bony structures undergo demineralisation, leading to alterations in facial contour and jaw structure.
Cell optimisation strategies
Bone optimisation
The gut microbiota, comprising trillions of microorganisms residing in the gastrointestinal tract, plays a multifaceted role in maintaining overall health and homeostasis. Recently, the emerging field of osteomicrobiology has shed light on the intricate relationship between the microbiota and bone health, offering promising insights into novel therapeutic strategies for addressing bone-related conditions.5
Research pioneered by Sjögren et al. 6-7 in 2012 was pivotal in establishing the gut microbiota as a key regulator of bone mass, paving the way for subsequent investigations into the mechanisms by which microbiota influence skeletal maturation, ageing, and pathological bone loss.
The mandibular bone, a crucial component of facial structure and support, is susceptible to age-related bone loss and structural changes.
Recent studies have revealed intricate crosstalk between the gut microbiota and bone metabolism, mediated through various signalling pathways and molecular mechanisms. Dysbiosis, or imbalance in the gut microbiota composition, has been implicated in the development of bone disorders such as osteoporosis and osteopenia.
There have even been suggestions of a possible relationship between periapical lesions as dental foci and rosacea.8
This growing body of evidence underscores the importance of considering the microbiome in the context of bone remodelling and structural integrity. By rebalancing the oral microbiota, it may be possible to optimise structural aspects of the mandibular bone, thereby preserving facial harmony and contour.
Therapeutic approaches:
1 Probiotics and prebiotics: Probiotic supplementation with beneficial bacteria strains, along with prebiotic fibres to nourish these microbes, may help restore microbial balance and promote bone health. Certain probiotic strains have been shown to enhance bone density and reduce the risk of osteoporosis in animal models and clinical studies. You can assess the oral microbiome through testing. You can use oral supplementation. There are also probiotic toothpastes. It’s worth encouraging patients to use bamboo rather than plastic toothbrushes and avoid oral mouthwashes, which sterilise the mouth.
2 Dietary interventions: A diet rich in fibre, fermented foods, and nutrients essential for bone health, such as calcium, vitamin D, and vitamin K, can support a diverse and balanced gut microbiota. Incorporating foods like yoghurt, kefir, sauerkraut, leafy greens, and fatty fish can provide beneficial nutrients and promote bone resilience. You also want to think about supplements like strontium which helps to mitigate bone loss.
3 Microbiome-targeted therapies: Emerging microbiome-targeted therapies, including faecal microbiota transplantation (FMT) and microbial-based therapeutics, hold promise for modulating the gut microbiota and improving bone health. These innovative approaches aim to harness the therapeutic potential of the microbiome to prevent and treat bone-related disorders.
4 Lifestyle modifications: Lifestyle factors such as regular exercise, adequate sleep, stress management, and avoidance of tobacco and excessive alcohol consumption can positively influence the gut microbiota and support bone health. Engaging in weight-bearing exercises and strength training can help maintain bone density and strength. Stress management is also key. When people are stressed, they often grind their teeth (bruxism). Implementing meditative practice and a morning routine can be key in these patients, not just botulinum toxin and mouth guards.
Muscle optimisation:
Muscular ageing presents a range of changes in the musculature of the face, contributing to visible signs of ageing such as sagging skin, wrinkles, and loss of facial volume. The nature of the muscle fibres changes, and they lose their contractility. These changes are attributed to a reduction in muscle mass, alterations in metabolism, and an increase in adipose tissue. One area particularly affected is the orbicularis muscle, responsible for controlling movements around the lips and eyes. As this muscle weakens and loses tone with age, it can lead to a noticeable slackening of the skin in these regions, resulting in the formation of fine lines, wrinkles, and a loss of facial definition.
To combat the effects of muscular ageing and promote a more youthful appearance, implementing facial exercises, commonly referred to as "face gyms," can be highly beneficial. These exercises target specific facial muscles, helping to strengthen and tone them, thereby improving muscle definition and elasticity. By regularly engaging in targeted facial exercises, individuals can counteract the natural decline in muscle mass and maintain a firmer, more lifted appearance.
Fat pad preservation:
Facial fat pads play a critical role in maintaining facial volume, contour, and youthful appearance. These fat compartments, including both superficial and deep fat pads, provide structural support, cushioning, and aesthetic balance to the face. However, with ageing, changes in fat distribution and volume loss can lead to a loss of facial fullness and contour, contributing to visible signs of ageing such as sagging skin, hollowed cheeks, and nasolabial folds.9-11
Ageing and other factors such as genetics, lifestyle, and hormonal changes can lead to alterations in facial fat distribution and volume. The gradual loss of fat in the superficial and deep fat pads results in a deflated appearance, accentuating facial lines and contours.
The use of GL1 agonists has recently been in the news, but people are getting what’s been coined” Ozempic face”.12 And it is not just drugs that can cause facial wasting; excessive exercise can, too. You may have heard the term “runner’s face”, which refers to changes in the facial appearance that some runners may experience over time, including leathery, saggy, ageing, lean, and tired-looking skin.
Strategies for fat pad preservation:
1. Dietary interventions
A balanced diet rich in essential nutrients, antioxidants, and healthy fats can support adipose tissue health and preserve facial fat volume. Incorporating foods high in omega-3 fatty acids, such as fatty fish, nuts, and seeds, can promote skin and tissue elasticity.
2. Lifestyle modifications
Maintaining a healthy lifestyle, including regular exercise, adequate hydration, and stress management, can help prevent premature ageing and support overall tissue health. Avoiding smoking and excessive alcohol consumption can also prevent collagen degradation and loss of facial fat. This includes stabilising weight and avoiding yo-yoing. Avoiding extreme.
3. Hormone balancing – Avoiding cortisol peeks is also key. A high release of hormones, especially cortisol, is a cause of moon face. This is called hyperadrenocorticism or hypercortisolism.
Conclusion
Facial ageing is a multifaceted process influenced by a combination of intrinsic and extrinsic factors. As clinicians, we should be educating our patients and delivering a really good consultation. Adopting a comprehensive approach to cell optimisation, encompassing bone, muscle, fat, skin, and broader cellular milieu considerations, is essential for effective anti-ageing interventions. By addressing underlying cellular mechanisms before treating the end organ, such as the skin, practitioners can achieve more holistic and long-lasting rejuvenation outcomes, promoting overall facial harmony and vitality.
References
1. Chaudhary M, Khan A, Gupta M. Skin Ageing: Pathophysiology and Current Market Treatment Approaches. Curr Aging Sci. 2020;13(1):22-30. doi: 10.2174/1567205016666190809161115. PMID: 31530270; PMCID: PMC7403684.
2. Carlos López-Otín, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer. Hallmarks of aging: An expanding universe. Cell. Volume 186, Issue 2, 2023. Pages 243-278. ISSN 0092-8674. https://doi.org/10.1016/j.cell.2022.11.001.
3. López-Otín C, Kroemer G. Hallmarks of Health. Cell. 2021 Jan 7;184(1):33-63. doi: 10.1016/j.cell.2020.11.034. Epub 2020 Dec 18. Erratum in: Cell. 2021 Apr 1;184(7):1929-1939. PMID: 33340459.
4. Danby FW. Nutrition and aging skin: sugar and glycation. Clin Dermatol. 2010 Jul-Aug;28(4):409-11. doi: 10.1016/j.clindermatol.2010.03.018. PMID: 20620757.
5. https://www.frontiersin.org/articles/10.3389/fcimb.2021.751503/full
6. Sjögren, K., Engdahl, C., Henning, P., Lerner, U. H., Tremaroli, V., Lagerquist, M. K., et al. (2012). The Gut Microbiota Regulates Bone Mass in Mice. J. Bone Miner. Res. 27, 1357–1367. doi: 10.1002/jbmr.1588
7. Ohlsson, C., Sjögren, K. (2018). Osteomicrobiology: A New Cross-Disciplinary Research Field. Calcif. Tissue Int.102, 426–432. doi: 10.1007/s00223-017-0336-6
8. Sopi M, Meqa K. Association of dental foci of infection and rosacea: a case report. Gen Dent. 2019 Nov-Dec;67(6):52-54. PMID: 31658025.
9. Wollina U, Goldman A, Tchernev G. Fillers and Facial Fat Pads. Open Access Maced J Med Sci. 2017 Jul 18;5(4):403-408. doi: 10.3889/oamjms.2017.117. PMID: 28785319; PMCID: PMC5535644.
10. Rohrich RJ, Pessa JE. The fat compartments of the face:anatomy and clinical implications for cosmetic surgery. Plast Reconstr Surg. 2007;119(7):2219–2227.https://doi.org/10.1097/01.prs.0000265403.66886.54 PMid:17519724.
11. Kruglikov I, Trujillo O, Kristen Q, Isac K, Zorko J, Fam M, Okonkwo K, Mian A, Thanh H, Koban K, Sclafani AP, Steinke H, Cotofana S. The facial adipose tissue:a revision. Facial Plast Surg. 2016;32(6):671–682.https://doi.org/10.1055/s-0036-1596046 PMid:28033645.
12. https://www.medicalnewstoday.com/articles/ozempic-face
Facial ageing is an intricate process influenced by a myriad of factors, both internal and external.1 As we age, the face undergoes significant morphological changes affecting various tissue layers, including bone structure, muscle mass, fat distribution, and skin quality.1
To effectively address the multifaceted nature of facial ageing, a comprehensive strategy focusing on cell optimisation before treating the end organ, namely the skin and facial structures, is paramount.
What we have been taught and what we tell our patients needs to be much more holistic than it is. But what has become clear to me while writing this article is the lack of evidence around the importance of cell optimisation as part of that holistic approach.
This month, I will explore the topic as it pertains to the ageing of the deep structures, including bone, fat, and muscle. Next month, I will delve deeper into cell optimisation for treating the skin.
The ageing process: Internal and external factors
· Intrinsic factors
Intrinsic ageing stems from genetic predispositions and biological processes inherent to ageing. Factors such as hormonal changes, particularly the decrease in oestrogen levels during menopause, contribute to reduced collagen production and skin thickness. Additionally, cellular damage accumulates over time, leading to decreased turnover and functionality of cells crucial for maintaining skin health.
WOULD THERE BE A POSSIBILITY TO RECREATE THIS DIAGRAM?
The 12 hallmarks of ageing2 are:
1. Genomic instability
2. Telomere attrition
3. Epigenetic alterations
4. Loss of proteostasis
5. Disabled macroautophagy
6. Deregulated nutrient-sensing
7. Mitochondrial dysfunction
8. Cellular senescence
9. Stem cell exhaustion
10. Altered intercellular communication
11. Chronic inflammation
12. Dysbiosis
These hallmarks are interconnected among each other, as well as to the recently proposed hallmarks of health3, which include organisational features of spatial compartmentalisation, maintenance of homeostasis, and adequate responses to stress.
· Extrinsic factors
External factors, such as sun exposure, lifestyle choices, and environmental pollutants, accelerate skin ageing. Ultraviolet (UV) rays from the sun, especially UVA and UVB, induce collagen and elastin degradation, resulting in wrinkles, sagging, and uneven pigmentation. Lifestyle habits like smoking and excessive alcohol consumption further exacerbate skin damage by impeding blood flow and impairing the skin's ability to repair itself.
There are also digital toxins, such as blue light from devices, toxins from plastics, pesticides and chemicals sprayed onto our food. And sugar, which plays a major role in glycation (a topic we will explore further in next month’s article).4
The interaction between intrinsic and extrinsic ageing is what we see in aesthetics. We can either work at a cellular level and address ageing from an internal longevity perspective or focus on the extrinsic. But I believe we have a duty of care to ask about our patient's lifestyles. If you do not, you are not working holistically.
Mechanisms of facial ageing
There are two main types of mechanisms that play a role in facial ageing: tissue modification involving all components of the face and a global drop of the facial tissues. This topic is well reported and so I am not going to focus on it in this in this article.
· Tissue modification:
Facial ageing involves alterations in all components of the face, including the skin, muscles, fat pads, and bone structure. Skin elasticity diminishes, leading to fine lines, wrinkles, and sagging. Muscles experience hypotony, contributing to visible slackening, particularly around the lips and eyes. Fat distribution changes, with some areas experiencing volume loss while others exhibit progressive decline.
· Global drop of facial tissues:
The structural integrity of facial tissues, including the superficial musculoaponeurotic system (SMAS) and bony scaffolding, undergoes significant changes with age under the influence of gravity. Muscular ageing involves a reduction in muscle mass and metabolism, exacerbating facial sagging. Fatty tissue may decrease in certain regions, while bony structures undergo demineralisation, leading to alterations in facial contour and jaw structure.
Cell optimisation strategies
Bone optimisation
The gut microbiota, comprising trillions of microorganisms residing in the gastrointestinal tract, plays a multifaceted role in maintaining overall health and homeostasis. Recently, the emerging field of osteomicrobiology has shed light on the intricate relationship between the microbiota and bone health, offering promising insights into novel therapeutic strategies for addressing bone-related conditions.5
Research pioneered by Sjögren et al. 6-7 in 2012 was pivotal in establishing the gut microbiota as a key regulator of bone mass, paving the way for subsequent investigations into the mechanisms by which microbiota influence skeletal maturation, ageing, and pathological bone loss.
The mandibular bone, a crucial component of facial structure and support, is susceptible to age-related bone loss and structural changes.
Recent studies have revealed intricate crosstalk between the gut microbiota and bone metabolism, mediated through various signalling pathways and molecular mechanisms. Dysbiosis, or imbalance in the gut microbiota composition, has been implicated in the development of bone disorders such as osteoporosis and osteopenia.
There have even been suggestions of a possible relationship between periapical lesions as dental foci and rosacea.8
This growing body of evidence underscores the importance of considering the microbiome in the context of bone remodelling and structural integrity. By rebalancing the oral microbiota, it may be possible to optimise structural aspects of the mandibular bone, thereby preserving facial harmony and contour.
Therapeutic approaches:
1 Probiotics and prebiotics: Probiotic supplementation with beneficial bacteria strains, along with prebiotic fibres to nourish these microbes, may help restore microbial balance and promote bone health. Certain probiotic strains have been shown to enhance bone density and reduce the risk of osteoporosis in animal models and clinical studies. You can assess the oral microbiome through testing. You can use oral supplementation. There are also probiotic toothpastes. It’s worth encouraging patients to use bamboo rather than plastic toothbrushes and avoid oral mouthwashes, which sterilise the mouth.
2 Dietary interventions: A diet rich in fibre, fermented foods, and nutrients essential for bone health, such as calcium, vitamin D, and vitamin K, can support a diverse and balanced gut microbiota. Incorporating foods like yoghurt, kefir, sauerkraut, leafy greens, and fatty fish can provide beneficial nutrients and promote bone resilience. You also want to think about supplements like strontium which helps to mitigate bone loss.
3 Microbiome-targeted therapies: Emerging microbiome-targeted therapies, including faecal microbiota transplantation (FMT) and microbial-based therapeutics, hold promise for modulating the gut microbiota and improving bone health. These innovative approaches aim to harness the therapeutic potential of the microbiome to prevent and treat bone-related disorders.
4 Lifestyle modifications: Lifestyle factors such as regular exercise, adequate sleep, stress management, and avoidance of tobacco and excessive alcohol consumption can positively influence the gut microbiota and support bone health. Engaging in weight-bearing exercises and strength training can help maintain bone density and strength. Stress management is also key. When people are stressed, they often grind their teeth (bruxism). Implementing meditative practice and a morning routine can be key in these patients, not just botulinum toxin and mouth guards.
Muscle optimisation:
Muscular ageing presents a range of changes in the musculature of the face, contributing to visible signs of ageing such as sagging skin, wrinkles, and loss of facial volume. The nature of the muscle fibres changes, and they lose their contractility. These changes are attributed to a reduction in muscle mass, alterations in metabolism, and an increase in adipose tissue. One area particularly affected is the orbicularis muscle, responsible for controlling movements around the lips and eyes. As this muscle weakens and loses tone with age, it can lead to a noticeable slackening of the skin in these regions, resulting in the formation of fine lines, wrinkles, and a loss of facial definition.
To combat the effects of muscular ageing and promote a more youthful appearance, implementing facial exercises, commonly referred to as "face gyms," can be highly beneficial. These exercises target specific facial muscles, helping to strengthen and tone them, thereby improving muscle definition and elasticity. By regularly engaging in targeted facial exercises, individuals can counteract the natural decline in muscle mass and maintain a firmer, more lifted appearance.
Fat pad preservation:
Facial fat pads play a critical role in maintaining facial volume, contour, and youthful appearance. These fat compartments, including both superficial and deep fat pads, provide structural support, cushioning, and aesthetic balance to the face. However, with ageing, changes in fat distribution and volume loss can lead to a loss of facial fullness and contour, contributing to visible signs of ageing such as sagging skin, hollowed cheeks, and nasolabial folds.9-11
Ageing and other factors such as genetics, lifestyle, and hormonal changes can lead to alterations in facial fat distribution and volume. The gradual loss of fat in the superficial and deep fat pads results in a deflated appearance, accentuating facial lines and contours.
The use of GL1 agonists has recently been in the news, but people are getting what’s been coined” Ozempic face”.12 And it is not just drugs that can cause facial wasting; excessive exercise can, too. You may have heard the term “runner’s face”, which refers to changes in the facial appearance that some runners may experience over time, including leathery, saggy, ageing, lean, and tired-looking skin.
Strategies for fat pad preservation:
1. Dietary interventions
A balanced diet rich in essential nutrients, antioxidants, and healthy fats can support adipose tissue health and preserve facial fat volume. Incorporating foods high in omega-3 fatty acids, such as fatty fish, nuts, and seeds, can promote skin and tissue elasticity.
2. Lifestyle modifications
Maintaining a healthy lifestyle, including regular exercise, adequate hydration, and stress management, can help prevent premature ageing and support overall tissue health. Avoiding smoking and excessive alcohol consumption can also prevent collagen degradation and loss of facial fat. This includes stabilising weight and avoiding yo-yoing. Avoiding extreme.
3. Hormone balancing – Avoiding cortisol peeks is also key. A high release of hormones, especially cortisol, is a cause of moon face. This is called hyperadrenocorticism or hypercortisolism.
Conclusion
Facial ageing is a multifaceted process influenced by a combination of intrinsic and extrinsic factors. As clinicians, we should be educating our patients and delivering a really good consultation. Adopting a comprehensive approach to cell optimisation, encompassing bone, muscle, fat, skin, and broader cellular milieu considerations, is essential for effective anti-ageing interventions. By addressing underlying cellular mechanisms before treating the end organ, such as the skin, practitioners can achieve more holistic and long-lasting rejuvenation outcomes, promoting overall facial harmony and vitality.
References
1. Chaudhary M, Khan A, Gupta M. Skin Ageing: Pathophysiology and Current Market Treatment Approaches. Curr Aging Sci. 2020;13(1):22-30. doi: 10.2174/1567205016666190809161115. PMID: 31530270; PMCID: PMC7403684.
2. Carlos López-Otín, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer. Hallmarks of aging: An expanding universe. Cell. Volume 186, Issue 2, 2023. Pages 243-278. ISSN 0092-8674. https://doi.org/10.1016/j.cell.2022.11.001.
3. López-Otín C, Kroemer G. Hallmarks of Health. Cell. 2021 Jan 7;184(1):33-63. doi: 10.1016/j.cell.2020.11.034. Epub 2020 Dec 18. Erratum in: Cell. 2021 Apr 1;184(7):1929-1939. PMID: 33340459.
4. Danby FW. Nutrition and aging skin: sugar and glycation. Clin Dermatol. 2010 Jul-Aug;28(4):409-11. doi: 10.1016/j.clindermatol.2010.03.018. PMID: 20620757.
5. https://www.frontiersin.org/articles/10.3389/fcimb.2021.751503/full
6. Sjögren, K., Engdahl, C., Henning, P., Lerner, U. H., Tremaroli, V., Lagerquist, M. K., et al. (2012). The Gut Microbiota Regulates Bone Mass in Mice. J. Bone Miner. Res. 27, 1357–1367. doi: 10.1002/jbmr.1588
7. Ohlsson, C., Sjögren, K. (2018). Osteomicrobiology: A New Cross-Disciplinary Research Field. Calcif. Tissue Int.102, 426–432. doi: 10.1007/s00223-017-0336-6
8. Sopi M, Meqa K. Association of dental foci of infection and rosacea: a case report. Gen Dent. 2019 Nov-Dec;67(6):52-54. PMID: 31658025.
9. Wollina U, Goldman A, Tchernev G. Fillers and Facial Fat Pads. Open Access Maced J Med Sci. 2017 Jul 18;5(4):403-408. doi: 10.3889/oamjms.2017.117. PMID: 28785319; PMCID: PMC5535644.
10. Rohrich RJ, Pessa JE. The fat compartments of the face:anatomy and clinical implications for cosmetic surgery. Plast Reconstr Surg. 2007;119(7):2219–2227.https://doi.org/10.1097/01.prs.0000265403.66886.54 PMid:17519724.
11. Kruglikov I, Trujillo O, Kristen Q, Isac K, Zorko J, Fam M, Okonkwo K, Mian A, Thanh H, Koban K, Sclafani AP, Steinke H, Cotofana S. The facial adipose tissue:a revision. Facial Plast Surg. 2016;32(6):671–682.https://doi.org/10.1055/s-0036-1596046 PMid:28033645.
12. https://www.medicalnewstoday.com/articles/ozempic-face
