The Most Advanced Anti Aging Products/Treatments Available to us Today

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Aging, or senescence, is the gradual deterioration of biological capability as a function of
age. Though lower organisms, such as bacteria and even some plants, exhibit immortality in some
capacity (negligible senescence or clonal immortality), most organisms characterized by a high
degree of complexity and organization do inevitably age. Aging has been a reality and source of
anxiety in human societies for millennia, and while no intervention has shown any demonstrable
ability to halt or reverse the aging process, several modern experimental avenues have slowed
down certain indications of aging in the laboratory setting, or otherwise generated organismal
strains with greater-than-normal lifespans.

Two modalities of cellular aging can contribute to the overall aging of the organism. The
first of these is damage-based, wherein the effects of aversive environmental stimuli accumulating
over the course of a lifetime cause a loss of function. This impairment is accidental, if occasionally
unavoidable, and includes damage by way of ultraviolet light and oxidative stress on the
biomolecular machinery of mitochondrial or genetic material. The second of these routes is
programmed aging, coded by genetic markers to reduce the capability of older members. While
potentially unsettling, the notion of aging as a selected-for, beneficial trait in a population is well
founded; aged family members can contribute to the rearing of new offspring without reproducing themselves, and their eventual deaths liberate resources, ultimately increasing the average fitness of the group.

Anti-aging experiments, therefore, will seek to act upon one of these routes. Less research
has been invested into affecting the damage-based route of aging, simply because avoidance of the
aversive stimuli appears more effective than reversing their effects, and because the effectiveness
of antioxidant foods (i.e. blueberries, nuts, etc.) is inconclusive in life-extension, despite their
theoretical capacity to limit the damage of oxidative stress at the cellular level. Far more promising
is the potential of reversing programmed cellular senescence. Several cellular pathways have been
implicated in the process, including telomere shortening, the mTOR autophagy pathway as
implicated by calorie intake and restriction, epigenetic DNA modification, to name a few.
Telomeres are one of the more popular cellular components to be associated with aging.
Telomeres are sections of noncoding or ‘junk’ genetic material deposited at the end of each
chromosome. These junk sections become relevant because the genetic replication cycle is
startlingly flawed. During the replication event, the enzymes responsible for duplicating the DNA
operate such that a small amount of genetic material is cut off and lost at the end of each strand.
The telomeres act as disposable buffers to this process, being truncated with every cycle, and while
newborns and children contain an enzyme which rebuilds these sections (telomerase), the enzyme
is notably absent at effective concentrations in adults. The theory goes on to suggest that when the
telomeres are totally exhausted, the coding portions of DNA begin being cut into, are
compromised, and then losses of function ensue. This makes telomere shortening an attractive
early target for programmed aging; if the telomeres can be extended in adults or telomerase
reactivated, perhaps the necessary genetic material could be kept safe. However, while Richard
Cawthon in 2003 discovered that those with longer telomeres tend to live longer than those with
short telomeres, it not known whether short telomeres signify of cellular age or truly contribute to
the aging process. Further research by Nordfjäll in 2009 and Biasco earlier in 1997 demonstrated
that mice lacking the telomerase enzyme even as newborns do not suffer shorter lifetimes, and that
while most humans experience this telomere truncation, a third of participants paradoxically
showed no telomere shortening as they aged, though age they did nevertheless. Additional
telomere research would be required to establish a biomolecular clock therein.

Figures:

Figure 1. Telomere Shortening Diagram Figure 2. mTOR Pathway Schematic
Mainous, American Journal of Hematology, Garciá-Arencibia, Seminars in Cell & Developmental 2013
Biology, 2010

Figure 3. DNA Methylation Diagram Figure 4. Rim15/Ras2 Is Required for Chronological Life
Span Extension and Cellular Protection
http://www.nccri.ncc.go.jp/en/divisions/
201308epigenomics/14carc01_1.html Wei, PLoS Genet, 2008
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A second cellular pathway is implicated with calorie restriction. The restriction of caloric
intake leads to longer lifespans, in a manner that is unrelated to the various metabolic disorders
caused by overeating. While the cause of the effect that is unclear, researchers lead by Fontana in
2010 found that it is likely mediated by the nutrition sensing function of the mTOR pathway.
mTOR is a protein that inhibits autophagy, the degradation of the cell by the cell. Researchers
found that when organisms restrict their diet, mTOR activity is reduced, which causes an increased
of autophagic behavior. Despite it being a degradation of the cell, autophagy is a controlled
degradation that increases longevity, as the cell parts degraded through autophagy are recycled and
regrown. This prevents the cell from entering ‘benign senescence,’ a non-functional state that
secretes various toxic agents, and may cause the losses-of-function associated with aging. Caloric
restriction of 70% of what would be consumed at the pleasure of the organism cause these positive
effects. Researchers hypothesize that the restriction decreases mTOR activation through insulin
sensitivity, as mTOR has been shown to impair spikes of glucose concentration in the blood.
Therefore, longevity may be associated with caloric restriction and insulin sensitivity by inhibiting
mTOR, which in turns allows autophagy to occur more frequently. As suggested by Johnson in
2013, inhibition of the mTOR pathway would additionally reduce levels of reactive oxygen species
on the body, which otherwise could damage genetic material. Additionally, a variation in the gene
FOXO3A has a positive effect on the life expectancy of humans, and is found frequently often in
people living beyond 100 years of age, regardless of geographic location. FOXO3A acts on the
sirtuin family of genes which Ghosh in 2013 demonstrated to inhibit mTOR.
There is also a strong correlation of DNA methylation with age. Methylation is a type of
epigenetic modification, wherein genetic information is modified on a continual basis, rather than
being locked-in at conception. Horvath hypothesized that DNA methylation, which deactivated
sections of the genome, might represent cumulative effect of an epigenetic maintenance system
intended to gradually shut down the functional capabilities of the cell. Christensen in 2015 noted
that DNA methylation age of blood predicts all-cause mortality in later life. Furthermore, Occampo
in 2016 found that mice aged prematurely can be rejuvenated to a younger phenotype and their
lives extended by up to 30% by partially ‘resetting’ the methylation pattern in their cells (as a full
methylation reset lead to immortal cancerous cells). This resetting into a juvenile state was
experimentally achieved by activating the four DNA transcription factors (Sox2, Oct4, Klf4 and
Thatos 5
c-Myc) which have used for producing young animals from cloned adult skin cells. This epigenetic
research is promising in offering a great degree of control in the experimental manipulation, though
invading and demethylating various tissues in a living human presents its own difficulties.
There are several miscellaneous pathways and experimental modalities that may be
implicated in aging reversal. For example, a decreased Growth Hormone/Insulin-like Growth
Factor-1 signaling pathway is associated with increased life span in fruit flies, nematodes and mice.
The precise mechanism by which decreased GH/IGF-1 signaling increases longevity is unknown,
but various mouse strains with decreased GH and/or IGF-1 induced signaling share similar
phenotypes, including increased insulin sensitivity, enhanced stress resistance and protection from
carcinogenesis. As found by Junilla in 2013, the studied mouse strains with decreased GH
signaling showed between 20% and 68% increased longevity, and mouse strains with decreased
IGF-1 induced signaling revealed a 19 to 33% increase in life span when compared to control mice.
Additionally, the Ras2 gene may be similarly implicated. Excitingly, Wei found in 2008 that a
yeast mutant lacking the genes sch9 and ras2 showed a tenfold increase in lifespan under
conditions of calorie restriction. This is the largest increase achieved in any organism, yeast though
it might be. Lastly, UNSW researchers under Jun Li in 2017 have manipulated the cellular repair
factor NAD+ and achieved frog age-reversal, stating that human trials will begin in three months
at the time of writing.
Crossing the space from laboratory models, be they in vivo or in vitro, to human beings
presents a salient difficult in longevity research. For that reason, long-term longitudinal studies
offer the best ideas on what might affect change. Many aspects of programmed cell aging have
been isolated and are being worked on currently, and as the data continues being brought to light,
the picture will likely resolve. One certain thing, however, is that the various anti-aging creams,
tonics, or unguents that make their rounds through infomercials are either based entirely on
pseudoscience or attack the cellular components of aging in a limited and ultimately ineffectual
way. In any case, for now, the challenge of longevity remains an enigma for longevity researchers
themselves and the bioethicists that may oppose them.
###
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Citations
• Blasco, María A; Lee, Han-Woong; Hande, M.Prakash; Samper, Enrique; Lansdorp, Peter M; Depinho, Ronald A;
Greider, Carol W (1997). “Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA”.
Cell. 91 (1): 25–34
• Cawthon, RM; Smith, KR; O’Brien, E; Sivatchenko, A; Kerber, RA (2003). “Association between telomere length
in blood and mortality in people aged 60 years or older”. Lancet. 361 (9355): 393–95
• Christiansen, L (2015). “DNA methylation age is associated with mortality in a longitudinal Danish twin study”.
Aging Cell. 15 (1): 149–154
• Fontana L, Partridge L, Longo VD (2010). “Extending healthy life span—from yeast to humans”. Science. 328
(5976): 321–6
• Ghosh, H. S.; McBurney, M; Robbins, P. D. (2010). “SIRT1 Negatively Regulates the Mammalian Target of
Rapamycin”. PLoS ONE. 5 (2): e9199
• Hemann, M. T.; Greider, CW (2000). “Wild-derived inbred mouse strains have short telomeres”. Nucleic Acids
Research. 28 (22): 4474–8
• Johnson, Simon C.; Rabinovitch, Peter S.; Kaeberlein, Matt (2013). “MTOR is a key modulator of ageing and agerelated
disease”. Nature. 493 (7432): 338–45
• Jun Li, Michael S. Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P. Hubbard, Alvin J. Y. Ling, Luis A.
Rajman, Bo Qin, Zhenkun Lou, Vera Gorbunova, L. Aravind, Clemens Steegborn, David A. Sinclair (2017). “A
conserved NAD binding pocket that regulates protein-protein interactions during aging”. Science. 355 (6331):
1312-1317
• Junnila, RK; List, EO; Berryman, DE; Murrey, JW; Kopchick, JJ (2013). “The GH/IGF-1 axis in ageing and
longevity”. Nat Rev Endocrinol. 9 (6): 366–76
• Mainous AG, Wright RU, Hulihan MM, Twal WO, McLaren CE, Diaz VA, McLaren GD, Argraves WS, Grant
AM. (2013). “Telomere length and elevated iron: the influence of phenotype and HFE genotype”. Am J Hematol.
88 (6):492-6
• Moisés García-Arencibia, Warren E. Hochfeld, Pearl P.C.Toh, C.Rubinsztein. (2010) “Autophagy, a guardian
against neurodegeneration” Seminars in Cell & Developmental Biology. 21: 691-8
• Nordfjäll, K; Svenson, U; Norrback, K. F.; Adolfsson, R; Lenner, P; Roos, G (2009). “The Individual Blood Cell
Telomere Attrition Rate is Telomere Length Dependent”. PLoS Genetics. 5 (2): e1000375
• Ocampo, A.; et al. (2016). “In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming”. Cell.
167 (7): 1719–1733
• Witzany, G (2008). “The viral origins of telomeres, telomerases and their important role in eukaryogenesis and
genome maintenance”. Biosemiotics. 1: 191–206
• Wei M, Fabrizio P, Hu J, Ge H, Cheng C, Li L, Longo VD (2008). “Life span extension by calorie restriction
depends on Rim15 and transcription factors downstream of Ras/PKA, Tor, and Sch9”. PLoS Genet. 4 (1): 139–
149

The Best Anti-Aging Treatments in the World (2017)

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Aging is a natural process of growing older in every human. Aging of skin is one of the most common reasons leading people to seek plastic surgery. Many over-the-counter anti-aging products are advertised boastfully, misleading a lot of customers. Today, we’ll have a closer look at the products that proved to be most effective in reducing the process of aging.

What are the causes of skin aging?

Two causes lead to skin aging: the intrinsic aging of the skin which relates to our genetic changes, and environmental and lifestyle processes. The natural aging process plays an important role. Over the time, we will notice that our skin become thinner and drier, causing wrinkles on our face. Environmental and lifestyle choices like sun exposure and smoking can be a reason for our skin to age prematurely (1).

There are a variety of topical preparations available for sale or being studied for ameliorating aging skin. According to Dr. Allen, they include retinoids, tretinoin (Retin-A), tretinoin emollient cream (Renova), adapalene, alpha-hydroxy acid (AHA), and salicylic acid. Other useful agents are vitamin C (Cellex-C), vitamin K (Ethocyn), and topical hormone treatments (2).

Vitamin A Derivatives

Vitamin A derivatives are natural antioxidants in the skin. The biologically active form is retinoic acid or tretinoin (Retin-A). Retinoic acid helps proliferate the outer layer of the skin, keratinization, and peeling. It also modifies keratin synthesis, fibroblastic proliferation, and collagen metabolism (1).

In a study by Varani and colleagues in 2000, 53 participants with the ages of over 80 applied 1% retinol for 7 days. The results demonstrated that vitamin A helped stimulate collagen synthesis in naturally aged skin compared with the controlled groups (3).

In another clinical study by Creidi and colleagues, 40 patients applied 0.5% retinaldehyde to the skin for 18 weeks. The research team found that wrinkles, surface stiffness and dryness of the “crow’s feet” area had been reduced (4).

Vitamin B

There have been few clinical studies about the effects of vitamin B on anti-aging. To evaluate the effect of topical niacinamide on skin appearance and aging signs, like wrinkles, yellowing, and elasticity, 50 women took part in a study. They applied niacinamide B3 daily to one side of their faces and compared it to the other side as a control. After 12 weeks, the results showed significant improvements in fine lines and wrinkles, hyper-pigmented spots, red blotchiness, and skin yellowing (5).

Vitamin C

Vitamin C is known as one of the most popular vitamins in well-designed studies about aging, and is proven to be effective in anti-aging.

In a 3-month, randomized, double-blind, vehicle-controlled study by Traikovich, 19 volunteers were asked to apply topical vitamin C on one side of their faces, and vehicle serum to the other side for three months. Topical vitamin C and serum vehicle were unlabeled to participants. The researcher concluded vitamin C provided significant improvements compared with the untreated hemiface regarding surface texture, fine wrinkling, tactile roughness, coarse rhytids, skin laxity, and sallowness (6).

Alpha-hydroxyl Acids

We have commonly seen alpha-hydroxyl acids used in cosmetics under the forms of glycolic acid and lactic acid (7).

Stiller and colleagues conducted a double-blind vehicle-controlled randomized clinical trial. Seventy four women applied 8% glycolic acid or 8% L-lactic acid creams twice daily to the face and outer forearms for 22 weeks. Patients had some facial improvements to sun-damaged skin compared with the placebo. On their forearms, treatment with glycolic acid cream or L-lactic acid cream ameliorated the overall severity of sun-damaged skin (8).

Pentapeptides

In a double-blind, placebo-controlled study, 0.005% pal-KTTS was applied to the right eye area of female volunteers twice a day for 28 days. The result revealed a decrease in wrinkle depth, wrinkle density, and skin rugosity by 18%, 37%, and 21% respectively (9).

Moisturizers

Moisturizers such as petrolatum, glycerin (glycerol), nicotinamide cream with white petrolatum have been proven in multiple studies that they help increase skin hydration and improve skin health (10, 11).

Newer botanicals

Polyphenols include: anthocyanins, bioflavonoids, proanthocyanidins, catechins, hydroxycinnamic acids, and hydroxybenzoic acids (12). Numerous anti-aging creams combine these compounds. Other newer botanicals require more research to formulate conclusions that can be extended to their topical application (13) (table below).

Compound

Findings

Grape seed extract

Grape seed extract accelerated human healing (14, 15).

Tree bark

Witch hazel (Hamamelis virginiana) bark extract applied to the irradiated skin for 3 days resulted in a decrease in erythema (16).

Soy extract

Genistein applied to dorsal skin 60 min before UVB radiation blocked erythema and discomfort (17).

Green tea

Topical application decreased UVB-induced inflammation and myeloperoxidase activity in skin and decreased pyrimidine fibers (18).

Table. Photoprotective potential of commonly used botanicals

Conclusion

There are many anti-aging products marketed. Some of them have proven to be effective based on some reliable research studies. These include vitamin A derivatives, vitamin B, vitamin C, alpha-hydroxyl acids, pentapeptides, moisturizers such as petrolatum, glycerin (glycerol), nicotinamide cream with white petrolatum, and some newer supplements.

References

1. Torras H. Retinoids in aging. Clinics in Dermatology. 1996;14(2):207-15.

2. Gendler EC. TOPICAL TREATMENT OF THE AGING FACE. Dermatologic Clinics. 1997;15(4):561-7.

3. Varani J, Warner RL, Gharaee-Kermani M, Phan SH, Kang S, Chung JH, et al. Vitamin A antagonizes decreased cell growth and elevated collagen-degrading matrix metalloproteinases and stimulates collagen accumulation in naturally aged human skin. The Journal of investigative dermatology. 2000;114(3):480-6.

4. Creidi P, Vienne MP, Ochonisky S, Lauze C, Turlier V, Lagarde JM, et al. Profilometric evaluation of photodamage after topical retinaldehyde and retinoic acid treatment. Journal of the American Academy of Dermatology. 1998;39(6):960-5.

5. Bissett DL, Oblong JE, Berge CA. Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al]. 2005;31(7 Pt 2):860-5; discussion 5.

6. Traikovich SS. Use of topical ascorbic acid and its effects on photodamaged skin topography. Archives of otolaryngology–head & neck surgery. 1999;125(10):1091-8.

7. Van Scott EJ, Ditre CM, Yu RJ. Alpha-hydroxyacids in the treatment of signs of photoaging. Clinics in Dermatology. 1996;14(2):217-26.

8. Stiller MJ, Bartolone J, Stern R, et al. Topical 8% glycolic acid and 8% l-lactic acid creams for the treatment of photodamaged skin: A double-blind vehicle-controlled clinical trial. Archives of Dermatology. 1996;132(6):631-6.

9. Lintner K. Cosmetic or dermopharmaceutical use of peptides for healing, hydrating and improving skin appearance during natural or induced ageing (heliodermia, pollution). Google Patents; 2003.

10. Gloor M, Gehring W. Increase in hydration and protective function of horny layer by glycerol and a W/O emulsion: are these effects maintained during long-term use? Contact dermatitis. 2001;44(2):123-5.

11. Fluhr JW, Gloor M, Lehmann L, Lazzerini S, Distante F, Berardesca E. Glycerol accelerates recovery of barrier function in vivo. Acta dermato-venereologica. 1999;79(6):418-21.

12. Manach C, Williamson G, Morand C, Scalbert A, Remesy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American journal of clinical nutrition. 2005;81(1 Suppl):230s-42s.

13. Huang CK, Miller TA. The Truth About Over-the-Counter Topical Anti-Aging ProductsA Comperhensive Review. Aesthetic Surgery Journal. 2007;27(4):402-12.

14. Li WG, Zhang XY, Wu YJ, Tian X. Anti-inflammatory effect and mechanism of proanthocyanidins from grape seeds. Acta pharmacologica Sinica. 2001;22(12):1117-20.

15. Khanna S, Venojarvi M, Roy S, Sharma N, Trikha P, Bagchi D, et al. Dermal wound healing properties of redox-active grape seed proanthocyanidins. Free radical biology & medicine. 2002;33(8):1089-96.

16. Deters A, Dauer A, Schnetz E, Fartasch M, Hensel A. High molecular compounds (polysaccharides and proanthocyanidins) from Hamamelis virginiana bark: influence on human skin keratinocyte proliferation and differentiation and influence on irritated skin. Phytochemistry. 2001;58(6):949-58.

17. Wei H, Saladi R, Lu Y, Wang Y, Palep SR, Moore J, et al. Isoflavone genistein: photoprotection and clinical implications in dermatology. The Journal of nutrition. 2003;133(11 Suppl 1):3811s-9s.

18. Katiyar SK, Perez A, Mukhtar H. Green tea polyphenol treatment to human skin prevents formation of ultraviolet light B-induced pyrimidine dimers in DNA. Clinical cancer research : an official journal of the American Association for Cancer Research. 2000;6(10):3864-9.