The concept of anti-aging may encompass many areas, approaches, and lifestyle attributes. I suppose due to the marketing influences, when we think and speak about anti-aging, typically anti-aging supplements and products are the first things that come to mind. 
And, frankly, that area is where my anti-aging interests first originated some 15 years ago.

As my body of knowledge and experience in the field expanded, so did my philosophy and methods. 
​
It is evident to me now that the anti-aging supplements, as effective as some of them truly are, are the tip of the iceberg. The pyramid below depicts the framework I now use to approach the anti-aging lifestyle and priorities. 
Certainly, I do not view the spiritual component as for anti-aging only, it is a part of the overall path and growth. Nevertheless, no anti-aging journey is complete without it. 

The break-down of the activities and approaches given above is not necessarily clear cut. My objective was to convey the model I apply and to highlight the importance  of looking at a bigger picture, beyond just the anti-aging supplements and biohacking, rather than to provide a precise classification.
For example, taking an Omega-3 supplement may count as both a healthy lifestyle and an anti-aging extra effort. Doing yoga may be a part of the physical activity and a healthy lifestyle, but may also contribute to the peace of mind and spiritual health. Fasting spans across all three layers.

As a side note, the field of medical aesthetics with its multitude of face, skin and body rejuvenation treatments, for the most part, can be and is also referred to as anti-aging.
​I consider that area "rejuvenation treatments" and did not include it into the anti-aging framework. Still, rejuvenation treatments make many people happy (and that is what counts), and there is a lot of face, skin, body aging and anti-aging information at Medical Aesthetics Information Platform and Solutions.

If you have no preference where to start with your anti-aging efforts, I would suggest starting at the layer of the spiritual and psychological health, whatever your preferred tools are. 
If the "mind and spirit first" approach is not for you at this point in life, like it was not for me 15 years ago, start (or continue) whatever aspect you feel like the most right now, because that is your inner guide as to what the best place for you to start with is.

​Namaste.

"Do you know any proven ways to slow down and reverse hair loss?"
"I am working out and eating healthy. Yet I am seeing signs of aging on my face. Why? And what can I do about it?"
I have been receiving many private messages from men with questions similar to those ones and decided to write a separate post on the matter.
​In this post: male facial aging concerns - anti-aging in general and facial aging; male facial aging - three lines; rejuvenation options; information resources; male medical aesthetics is a growing trend; basic anti-aging advice. 
​

I will begin by saying that unfortunately this is not entirely an anti-aging question. 

Yes, nutrition, physical exercise, sleep, alcohol consumption, smoking, anti-aging supplements, fasting, etc influence how young a face looks; however, a person can be perfectly healthy and fit and have an amazing body, and the face will still show signs of aging due to genetics, environmental factors, prior weight gain - weight loss cycles, or, what I call, tear-and-wear. 
​
There are several anatomical  layers on the face: several layers of skin (epidermis and dermis), superficial fat pockets, muscles, deep fat pockets, connective tissue and, possibly, interstitium, and the bones. While the lifestyle and anti-aging regimens have a large impact, the anatomical layers still age, and they age at a different pace, under the influence of different factors. 

​Facial and body rejuvenation above and beyond what is/can be achieved with the lifestyle changes and anti-aging supplements is addressed by the medical branch called medical aesthetics. 
​

​MDs who specialize in the male facial aesthetic treatments and know what their clients want, use an almost coined phrase, "Men are concerned with three lines: jawline, eyeline, and hairline." (unlike women who are concerned with so much more :))
​
Jawline - lost definition of the lower face, facial sagging and/or fat accumulation under the chin/jaw. 
Eyeline - dark circles, hollowness or puffiness, "I look tired".
Hairline - the hair loss that frequently starts in 20s and affects at least 50% of men.
I will also add the fourth one - a deep line(s) between the eyebrows. ​
​

It is always better to prevent an issue than to correct it, and at the end of the blog post I included some basic anti-aging advice.
​For those who are already facing the issues, modern aesthetic medicine and cosmetic industry offer numerous options, including inexpensive and non-invasive ones, for the facial rejuvenation and hairline restoration. 

The full high-level lists of options to treat the three lines are -
Hairline:

• topical Minoxidil; 
• topical peppermint oil and/or lavender oil; 
• topical caffeine solution; 
• a range of vitamins and minerals; 
• specifically formulated oral hair growth supplements;
• oral Finasteride; 
• Low Level Laser Therapy (sometimes combined with LED);
• PRP/PRFM (Platelet Rich Plasma/Platelet Rich Fibrin Matrix) injections;
• SVF (stromal vascular fraction) injections;
• autologous micronized or unprocessed fat injections, alone or combined with SVF or PRP (our fat is the richest source of stem cells in our bodies);
• micro needling with an electric device or at-home micro needling with a derma roller, alone or combined with topically applied immediately before and after the procedure PRP or growth factors/stem cells;
• surgical hair transplantation. 

Eyeline: 

• high quality eye creams and serums to hydrate and plump the skin and trigger collagen and elastin production and hyaluronic acid saturation;
• LED to gently stimulate skin rejuvenation;
• injection of specifically formulated for the eye area hyaluronic acid fillers;
• fat transfer;
• a more refined procedure of micronized fat transfer or fat with SVF transfer;
• lower eyelid surgery, alone or combined with fat transfer.

Jawline:

• under the chin injections of Kybella to dissolve fat;
• device enabled fat melting procedures;
• device enabled skin tightening under the chin;
• micro current treatments to tone and lift facial muscles to improve the overall definition of the face including the jawline; 
• fat transfer or volumetric filler injections to replace lost volume and lift the skin (that will improve the jawline too);
• RF and Ultrasound Device skin (dermis) tightening procedures;
• surgical facelift;
• facial implants.

​Unfortunately, even in a long blog post, it is not possible to give an answer suitable for everyone as to what the best option is, not only because of the number of the options, but also because reasons for an aged look and the stage of aging vary from person to person, and the most suitable option also depends on the age of a patient and the budget. 

​Take the hair loss, for example.
​It may be tempting to give an advice like in many blogs, "use minoxidil 5%, it's inexpensive, and has a high likelihood of effectiveness".
The reality is that - 

1. 10% Minoxidil may be more effective (yes, there are no clinical studies, it's not approved by FDA, however, Minoxidil has been shown to be dose-dependent),
2. Some people have an allergic reaction to Minoxidil (itching),
3. Some men do not see results from Minoxidil, for example, because the reason for their hair loss is not androgenetic (androgenic) alopecia or it is just not effective for them;
4. Some men have so much on their plate that it is not realistic to apply the product twice-a-day for months;
5. Non-surgical treatments, if they work, only work on the areas where the dormant dying hair follicles still exist deep inside. If an area has had no hair for several years, meaning that the hair follicles are probably completely gone, non-surgical options are unlikely to produce results.

(Source: ​Topical Products for the Hair Growth. Minoxidil)
​
Every situation is different, and in the section below I included information sources for research on possible treatments.  In the end I also included a generic preventative facial anti-aging advice.
If you don’t have time for research and want information and advice geared precisely to your situation/question, I give private paid consultations on the phone (I have all the information starting with the facial anatomy, anatomy of the facial aging, and the treatment options, but I do not perform any treatments). ​
​

There is a lot of information on the facial aging and rejuvenation treatments at:

• Medical Aesthetics Information Platform and Solutions. MAIPS.com - Science based information centered around issue/area of concern with a large spectrum of options covered, the focus is on non-invasive options (not surgery);
• realself.com - Doctors answer questions on treatment options and surgery. I like the sheer volume and variety of questions and answers. The drawback is that doctors' opinions vary a lot depending on which technique/procedure they are proficient with. In my opinion, this is a great source to find a doctor once you are somewhat clear on the desired procedure;
• High level description of procedures by American Society of Aesthetic Plastic Surgery;
• High level description of procedures by American Society of Plastic Surgeons. 

​

In case you were curious... 
​There already are medical aesthetics clinics, and more are opening,  specializing in male procedures. In South America this was the case already 15-20 years ago; USA and Canada are starting to catch up. This is in addition to the medical aesthetics clinics, centers, spas, plastic surgery centers that service clients of both genders.
To clarify, aesthetic and cosmetic procedures include a wide range of non-surgical, non-invasive or minimally invasive options such as injectables and various device enabled treatments. 
​
​To elaborate on why there are separate clinics for men - 

• ​First, there are some differences between male versus female anatomy. There are no major differences in how treatments are performed on men versus women, however, the aesthetic goals vary. The idea is to make a man's face look younger while preserving its masculine features; and the treating doctor should have the aesthetic sense and vision for the male beauty and treat accordingly; 
• Second, some men don't want to be seen by women during the procedures;
• Men are often interested in body-contouring procedures as much as in the facial rejuvenation (and hence the clinic's offerings differ);
• There is also a growing demand for the sexual rejuvenation/enhancement treatments that are obviously different for men and women (not covered in this post).

​
​The point is that the mere fact that the number of those clinics grows is an indicator of the flourishing demand for the male aesthetic procedures, including facial ones. The statistics by American societies of plastic surgeons confirm the trend.

Reasons why men get interested in aesthetic treatments vary - 

• Some men go for procedures because their wives have been taking care of their faces, and at some point a husband starts looking like a father to his wife, and some couples want to address that. As a matter of fact, most referrals to medical aesthetics clinics that provide services to both genders are made by wives and girl-friends;
• ​An increasing number of people in their late 30s, and in 40s and 50s are back on the dating stage;
• Some other men, and women too, feel young at heart and are physically fit and they don't like a dissonance between that and the facial aging they see in a mirror;
• American culture that places an emphasis on youth and looks, and men are sometimes motivated by career considerations, wanting to be perceived as strong and vibrant at the workplace. 

Whatever the reason, worldwide, male rejuvenation/aesthetic/cosmetic procedures is a fast growing area of the medical aesthetics. A recent survey showed that 40% of men were interested or possibly interested in cosmetic procedures, 43% were not satisfied with facial appearance. And sales in men's grooming industry reached $50 billion in 2017. 

It is worth noting that men are more reluctant than women to reveal even to their peers that they had any cosmetic procedure done and they are less tolerant to the downtime after procedures. 
​

Just like with any anti-aging, the best strategy is to prevent rather than to correct. What measures above and beyond healthy lifestyle and broad-spectrum anti-aging approaches can be taken to delay the signs of facial aging? 

1. If you have light-colored skin, apply a sunblock or a broad-spectrum sunscreen of at least SPF30 whenever you go outside and the UV Index is over 4-6 (you can see it in any weather app) and wear sun-glasses. Exposure to strong UVA and UVB from sun ages skin, resulting in the destruction of collagen and elastin and in the accumulation of dark pigmentation. Those changes lead to wrinkles, lines, brown spots, overall aged looking skin. Strangely, the majority of SPF advertisements are still found in the magazines with female audience.
   
2. When in the sun, wear sun glasses. Squinting from bright sunlight speeds up development of the crow's feet wrinkles around the eyes.
3. ​Avoid (minimize) ups and downs with the weight, starting at the young age (18 - 20 years of age). Weight loss always results in a loss of fat in the deep fat pockets of the face. These deep fat pockets are not excessive fat, but a part of the facial structure that creates the youthful look. If you gain weight, these deep fat pockets do not get inflated as much as the rest of the fat deposits on the body. When you lose weight, these pockets get deflated at least at the same rate as elsewhere on the body. Thus, the cycling of weight gain - weight loss is a downward spiral for the look of the face. The same size outside tissue (skin) will be hanging on a smaller size frame (due to less fat volume inside).
4. Use a good moisturizer, facial cream, and eye cream starting in your 20s. Creams and serums will not help with the hair loss and the jawline, but they will help preserving the overall quality of the skin and the delicate skin around the eyes. The most basic and inexpensive are A) any basic Hyaluronic Acid Serum (search on amazon) - it hydrates and plumps the skin, also conceals superficial wrinkles; B) Vitamin C serum or a Retinoid (Vitamin A cream). Apart from these basic options, cosmetic industry offers hundreds of product lines, and some of them are designed specifically for men.  South Korea leads the planet in the quality and effectiveness of their cosmetic products, and you can use any cream typically advertised for women (skin is skin), or choose from the product lines designed for men. Missha is an expensive line, sold in the USA, has products for men.
5. ​For the hair loss prevention, if you are genetically predisposed to it, some hair doctors recommend using 2% Minoxidil.​
6. Take vitamins and minerals. Particularly, calcium, magnesium and vitamin D combined work to preserve the bones (the bones start deteriorating and the skull starts decreasing in size starting around the age of 60). 

Any comments, questions or suggestions are welcome. 

The Baltimore Longitudinal Study of Aging (BLSA) started in 1958 and is conducted by the Intramural Research Program of the National Institute on Aging (NIA), part of the National Institutes of Health at the U.S. Department of Health and Human Services. 
​It is the longest-running study of aging and longevity in the world, has involved over 3,000 participants and resulted in hundreds of scientific publications.
​
Majority of the studies on aging are cross-sectional: they compare participants in one age group to participants in another age group. The supremacy of BLSA is that it observes over decades changes in health of the participants thus reducing the distortion from external factors. The BLSA is considered a gold-standard for longitudinal and aging research. 
​

The core focus of the study is finding and defining what 'normal aging' is. There is a difference between disease later in life that results from improper lifestyle, nutrition etc and 'normal' aging - healthy tear-and-wear. Another major goal is to identify the relationship between aging and disease. 

As the National Institute of Aging put it, the idea is to establish "the true effects of aging and how to separate factors such as disease, socioeconomic disadvantage, [...] from the underlying biological or other mechanisms common to human aging".

People age differently, yet scientists were able to establish age-related changes that will be experienced by almost everyone. 

The value of the BLSA findings for those who are interested in increasing their own life span and health span is, among other things. in pinpointing the areas that may benefit from early intervention above and beyond simply healthy lifestyle. ​It is always easier to prevent than to correct.

1. ​'Normal" aging is NOT synonymous with disease. It is possible to grow old without really developing what is called age-related disease; 
2. People age differently. Besides lifestyle and disease, genetics affect how and how fast an individual ages; 
3. ​Arterial stiffening is an age related change, and it increases the risk of the cardiovascular disease. And then the cardiovascular disease, in its turn, accelerates even more the aging of the cardiovascular system;
4. Testing the levels of the free (not attached to proteins) Prostate Specific Antigen can establish the risk of the prostate cancer as long as five years before its actual onset;
5. ​Decline in cognitive abilities - abilities to think, learn, and remember - is a part of 'normal' aging;
6. Alzheimer disease is not, as we know, a part of normal aging. Early intervention may be useful and possible because we now know that AD is preceded by a sharp memory decline 7 years before the onset of the AD, and then by the second memory decline 2-3 years before the diagnosis;
7. An adult's personality does not change much after the age of 30 (and should you wish to change your personality, habits, and life outlooks, you need to consider measures that activate neuroplasticity);
8. Vision decline, particularly far acuity, is a part of a normal aging, independent of any disease;
9. Muscle quality declines as a part of normal aging, but it is also affected by obesity and neurological factors;
10. Decline in physical health is associated with decline in cognitive health.

​

Never hurts to remind ourselves  - 

1. Stay physically active;
2. Watch your weight and shape;
3. Eat healthy;
4. ​Experience positive emotions by participating in activities you enjoy;
5. ​Maintain close friendships with people who love and support you. 

​

Fabbri E, An Y, Zoli M, et al. Association Between Accelerated Multimorbidity and Age-Related Cognitive Decline in Older Baltimore Longitudinal Study of Aging Participants without Dementia. J Am Geriatr Soc. 2016;64(5):965-72.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882249/

Ferrucci L. The Baltimore Longitudinal Study of Aging (BLSA): a 50-year-long journey and plans for the future. J Gerontol A Biol Sci Med Sci. 2008;63(12):1416-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004590/
​
Gittings N. S., Fozard J. L. Age related changes in visual acuity. Experimental Gerontology. 1986;21(4-5):423–433. doi: 10.1016/0531-5565(86)90047-1.
https://www.ncbi.nlm.nih.gov/pubmed/3493168
​
Moore AZ, Caturegli G, Metter EJ, et al. Difference in muscle quality over the adult life span and biological correlates in the Baltimore Longitudinal Study of Aging. J Am Geriatr Soc. 2014;62(2):230-6.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945403/
​
Acessed on February 7 -9, 2019 - 

https://www.nia.nih.gov/research/blog/2014/04/valuable-data-resource-baltimore-longitudinal-study-aging

https://www.nia.nih.gov/health/what-do-we-know-about-healthy-aging​

​https://www.nia.nih.gov/research/labs/blsa/advances-aging-research

https://files.eric.ed.gov/fulltext/ED292030.pdf
​
​​http://medfac.tbzmed.ac.ir/uploads/User/5247/healthy_aging_lessons_from_the_baltimore_longitudinal_study_.pdf

For those unfamiliar with the topic, accumulation of senescent (old, damaged, no longer replicating) cells in our tissues and organs is one of the reasons why our organs lose their functionality and why we age. Not only those old cells malfunction, they also secret pro-inflammatory signals (Jian-Lin Res, 2009) and produce toxic substances into the extra-cellular environment, thus leading to many age-related diseases. Moreover, they translate the senescent phenotype to the neighboring cells suggesting to them to assume the same senescent expression.  

When we are young, our immune system promptly eliminates the senescent cells. As we grow older, this house-cleaning process slows down.  
Elimination of the senescent cells, along (ideally) with periodic activation of telomerase (telomere lengthening enzyme/process), is one of very promising anti-aging strategies. I will cover that approach in detail in one of later posts. 

A senolytic is a compound or a drug or a supplement that selectively kills senescent cells leaving healthy young cells unaffected. 

​Fisetin is a flavonoid, a polyphenol found in small concentrations in fruits and vegetables such as strawberry, apple, persimmon, grape, onion, and cucumber. See the fisetin content in food at the end of the post.
Fisetin is close in structure to quercetin, but not as well studied. ​

Besides its senolytic properties, Fisetin has also been long known to be an anti-oxidant and to have anti-inflammatory and anti-cancer properties (Maher P, 2015). In addition, Fisetin is not only neuroprotective like other flavonoids, which stems from their anti-oxidant properties, but it is also neurotrophic (causes growth of new brain cells) (Sagara, 2004).

​Studies on mice and human tissues have also identified that fisetin acts as a senolytic.
A recent study (Yousefzadeh M, 2018) looked at 11 promising senolytic compounds, including curcumin and quercitin, and found fisetin to be the most effective. 
 
The main findings and conclusions from the study were:

• Fisetin targets and destroys senescent cells both in mice and, ex vivo, in human fat tissue;
• Even with late in life intervention, mice fed with Fisetin lived 10-15% longer than control mice. That is a 50% increase in the remaining life after treatment with fisetin;
• Long-term administration of Fisetin led to higher glutathione levels (our natural powerful anti-oxidant);
• Fisetin decreased pro-inflammatory signaling.

Dosage. What we know - 

• To date, there are no completed studies (clinical trials) of fisetin on humans. The above study was done on mice and on human fat tissue placed in a petri dish;
• ​This publication (Anroop B, 2016), provides animal to human dose conversion ratios; and human to mice is 1-to-12 (mice dose [in "per kg of body weight"] divided by  12 should be considered for humans). We can use this conversion ratio to convert the dose in the mice study;
• In the above Fisetin study (Yousefzadeh M, 2018), normal/wild-type (vs. genetically engineered to have a pre-disposition to disease and health issues) mice were given orally intermittently (6 to 8 weeks of age, then 12 to 14 weeks of age) - 100 mg/kg of body weight. That was the dose found to be effective as a senolytic for the mice. That will be approximately 8.2 mg/kg of body weight in humans (100 mg/12). Translating that to a 60-kg/132 lb. human, that will be ~ 500 mg of Fisetin a day, or ~ 600 mg of Fisetin a day for a 75 kg/165 lb person, for extended periods of time;
• The above study also tested Fisetin on human fat tissue in a petri dish; the tissue was exposed to fesitin for 48 hours; the conclusion is that fisetin works on human tissue (not only on mice); what is unclear is what the oral dose would be to achieve the same tissue concentration and the senolytic effect; 
• Mayo Clinic is currently conducting a human trial of Fisetin: 20/mg/kg/day, orally for 2 consecutive days, for 2 consecutive months (2 cycles of two days with a month break) to see if it can reduce frailty and inflammation in elderly women. The 40 study participants are 70 to 90 years old. The dose translates to 1.2 g/d for a 60-kg/132 lb  person or 1.5 g/d for a 75 kg/165 lb person. 

Toxicity. How much is safe?
​

• Currently, none of the studies with Fisetin revealed any toxicity of the compound at any level. The maximum level of Fisetin tested in another mice study (Currais, 2014) was 2000 mg/kg of body weight orally, for 2 consecutive days (acute toxicity test). No signs of toxicity were observed with the Fisetin administration at that level.
• If we translate that into human dose: 14 g/d for a 60 kg/132lb person or 18 g/d for a 75 kg/165 lb person. Please keep in mind that those 14 and 18 g/d are a mathematical calculation - this dose has NOT been tested on humans. 

 
Other relevant studies and information:

• the average dietary intake of naturally occurring fisetin in fruit and vegetable is 0.1 - 1 mg/day;
• strawberries have the highest natural levels of fisetin. A clinical trial (Chen T, 2012) of 60 g/day of freeze-dried strawberries (approximately 9 - 10 mg of Fisetin a day; that is over 100 times less than the dose in the Mayo Clinic trial) showed a reversal of pre-cancerous lesions in humans and an improvement in several other health markers. Limitations: 1. it's unclear to what extent that anti-tumor effect stems from fisetin alone vs. also from other compounds in strawberries; 2. the anti-tumor dose and senylitic dose may be different. Having said that, consuming lots of strawberries may be an option for those who prefer to not take supplements;
• Fisetin is not a patented compound and is available from many nutraceutical companies as a supplement. 

What we have no information about

• Degree of the dose dependency of fisetin and the optimal dose. In other words, will fisetin be as effective or how much less effective in smaller doses? Or will it have even more senolytic (anti-aging) effect in larger doses? 
• The optimal dosage for the senolytic effect.

Summary

• Fisetin has been shown to be a very effective senolytic compound for mice, and may possibly be a very effective senolytic for humans;
• The dosage currently used in a clinical trial is 20 mg/kg of body weight for two consecutive days, then a month break and a second round. If you decide to try Fisetin, I would limit the dosage at the level used in that study;
• The orally administered dose that was found effective in mice as a senolytic will likely translate to 8.3 mg/kg of body weight in humans for prolonged periods of time;
  
• Lots of strawberries in a diet will provide a little bit of Fisetin for those who prefer food sources to supplements (a pound of fresh strawberries contains about 70 mg of Fisetin).  

​