They should start from fewer subjects, apply for a relatively short period of time, and focus primarily on safety and tolerability. This approach can provide early clues to promising compounds for potential candidates and then deserve longer or more detailed aging studies [ 5 ].

Over the past century, average human life span has increased substantially. It is clear that the exploration of new targets for these anti-aging agents based on biogerontology is a huge opportunity for the healthcare and pharmaceutical industries [ 7 ]. The present review would focus on the properties of slow aging and healthy life span extension of natural products from various biological resources, endogenous substances, drugs, and synthetic compounds as well as the mechanisms of targets for anti-aging evaluation, would discuss these bioactive compounds that could provide benefits in the aspect of healthy aging and potential role of life span extension.

Astaxanthin 1 is a kind of carotenoid that belongs to the subclass of xanthophyll. It is a nutrient with many clinical benefits and acts through unique cell membrane effects [ 8 ]. This compound quenches free radicals or neutralizes other oxidants by accepting or donating electrons without becoming a prooxidant or being damaged in the process.

Its linear structure and polar-nonpolar-polar layout enable it to be inserted precisely into the membrane and across the entire width. The polar structure is the ionone ring, which has a strong ability to scavenge free radicals or neutralize other oxidants, mainly in aqueous environments, or also in the absence of water [ 9 , 10 ].

The nonpolar intermediate segment acts as a series of conjugated carbon—carbon double bonds, giving the compound further oxidation resistance and the ability for the removal of high-energy electrons from free radicals and delocalization of their electron energy through carbon—carbon chains.

At this location, astaxanthin can intercept active molecules in the hydrophobic interior and at the hydrophilic boundary of the membrane. Astaxanthin has shown a variety of clinical benefits with good tolerability and safety. The results showed that oxidative DNA damage was inhibited, C-reactive protein and other inflammatory biomarkers were decreased, and tuberculin skin test immunity was enhanced [ 13 , 14 ].

In another trial, daily astaxanthin doses of 6, 12, or 18 mg decreased triglycerides and increased HDL cholesterol and improved blood flow in microcirculation models [ 15 ]. In a small clinical trial, it improved cognition and promoted the differentiation and proliferation of neural stem cells in culture [ 16 ].

Astaxanthin improved vision and eye adaptation in several randomized controlled trials in Japan [ 17 , 18 ]. In a double-blind, randomized controlled trials, the protective effect of astaxanthin on fertility and sperm function was evaluated.

The researchers recruited 30 men from infertile couples, the female partner in subjects showed no obvious reason for infertility. They were randomly assigned to either astaxanthin group 16 mg a day or a placebo group for 3 months. During this time, they were permitted to provide semen for intrauterine insemination and the pregnancies were recorded.

However, the pregnancy rate, a trial result that is most telling, reached In a randomized controlled trial, the effect of astaxanthin on functional dyspepsia was evaluated [ 20 ].

All patients were then randomly assigned to receive either 16 mg or 40 mg of astaxanthin daily or a placebo in a double-blind trial for 4 weeks.

Gastrointestinal symptoms: abdominal pain, dyspepsia, and reflux were assessed by the rating scale GSRS. The trial results were assessed by a standard questionnaire. Treatment lasted for 4 weeks, followed by follow-up after 4 weeks. There were no significant differences in the combined scores of abdominal pain, dyspepsia and reflux syndrome among the three groups.

The same results were found at the end of the follow-up. The researchers concluded that astaxanthin had no effect on FD overall. The clinical success of astaxanthin goes beyond protection against oxidative stress and inflammation, and could demonstrate its promise to slow age-related decline.

Astaxanthin cannot be produced in the human body and is mainly ingested through the diet, and almost all of the dietary intake containing astaxanthin comes from seafood.

In nature astaxanthin is produced by algae, bacteria and fungi. Because these primary producers are often used as food, the substance is concentrated at the top of the food chain. It turns the flesh, skin or exoskeleton of animals such as shrimp, krill, crayfish, lobster, crab, salmon and trout into a natural intense red illumination.

It is also fed as feed to farmed seafood for its coloring. Astaxanthin is also naturally present in the feathers of flamingos which are the characteristic color of quails and in their retinas [ 8 ].

Natural astaxanthin is mainly derived from commercially cultured single-celled algae Haematococcus pluvialis [ 21 ].

Synthetic astaxanthin is also emerging as an important product. Natural and synthetic astaxanthin differ in chemical composition, bioavailability, purity, or sensory quality.

Natural astaxanthin is variable and exists as stereoisomers of 3S, 30S and 3R, 30R, and in free form or esterified forms. The algae Haematococcus primarily produces the 3S and 30S isomers, which are also present in the free form in wild Atlantic salmon.

The yeast Pfaffia rhodozyma synthesizes mainly the 3R and 30R isomers, which are also occur in the esterified form in Antarctic krill. The vast majority of new dietary supplements approved by the FDA for natural astaxanthin use H.

pluvialis extracts. Natural astaxanthin extracts usually contain other carotenoids canthaxanthin, β-carotene, and lutein , which have related and similar biological activities depending on the source. Synthetic astaxanthin consists of a mixture of 3S, 30S, 3R, 30S, 3R and 30R isomers and may also contain traces of residual solvents and impurities [ 22 ].

Natural astaxanthin showed a good clinical safety profile, with no serious adverse side effects observed in any clinical studies, even at high doses 45 mg in 15 patients. In one clinical trial, at a dose of 30 mg, subjects were found to have red-colored stools and increased frequency of bowel movements.

Curcuma longa is a curry spice that originated in India. The rhizomes of Zingiber officinale Zingiberaceae , ginger, as one of the most popular spices, has been planted in China for thousands of years for spices and medicine [ 23 ].

In recent decades, they have attracted great interest because they contain biologically active curcuminoids curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcumin 2 is a kind of natural yellow pigment, is very rare in natural diketone coloring matter, have strong tinting strength, bright color, strong heat stability, safety, non-toxic, can be widely applied in cakes, sweets, drinks, ice cream, wine, and other foods as a colorant, is considered to be one of the most valuable natural edible pigment Scheme 1.

At the same time, it is also the World Health Organization and the Food and Agriculture Organization of the United Nations regulation of the use of high safety of natural pigments. Curcumin is a lipophilic plant polyphenol that has been shown to act as an anti-aging, anti-inflammatory, anti-cancer agent and antibiotic based on and in vivo studies and clinical trial results [ 24 ].

Curcumin comes in two tautomers, ketones—and enols. At both neutral and acidic pH, the ketone type dominates, while enol tautomer exists only in basic conditions. This can be explained by the formation of enol-type intramolecular hydrogen bonds [ 25 ].

Tetrahydrocurcumin was reported to extend the life span in a study for male mice [ 26 ]. It was confirmed that curcumin supplementation helps reduce some features of dementia in rodents. In adult mice, curcumin improved synaptic plasticity, neuronal repair, and hippocampal neurogenesis [ 27 ].

Another study showed that curcumin improved synaptic structure and quality in the hippocampal CA1 region of double transgenic mice [ 28 ].

Furthermore, curcumin can effectively reduce Aβ production in the double transgenic mice by inducing autophagy [ 29 ]. However, to date, no studies have evaluated the effects of curcumin on cognitive performance in humans.

There are over 15, publications on curcumin biological interactions, with about 50 published per week. Recently, an excellent review discussed an in-depth evaluation of curcumin, a potential new direction for research [ 30 ]. The article provides a review of the basic medicinal chemistry of curcumin and demonstrates that curcumin is an unstable, reactive, poorly bioavailable compound and therefore not a lead compound, but they do not rule out the possibility that crude curcumin extracts may be beneficial to human health.

The new study suggests that curcumin may affect the intestinal microflora, which is associated with a variety of chronic diseases.

This hypothesis has not been fully tested, but may eventually provide a focal point for research into the therapeutic effects of curcumin.

Morphine 3 is a substance found naturally in poppies Papaver somniferum. Despite side effects of respiratory depression, tolerance, and addiction, it remains one of the most widely used painkillers in medical clinics. In addition, the presence of endogenous morphine in animals is widely accepted, including invertebrates and vertebrates.

The effects of morphine on the lifespan of fruit flies were studied. The 0. MH supplementation on the 5th day after birth obviously prolonged the average lifespan of male flies at all studied concentrations. The female fruit flies treated with only 0. Together with earlier studies in mice, [ 32 ] morphine supplementation was found to extend life span in vertebrates and invertebrates.

Nordihydroguaiaretic acid 4 , isolated from the leaves of the Creosote shrub Larrea divaricata or Corillea tridentate , an evergreen desert plant widely found in the southern United States and the northern border region of Mexico, is a natural lignan. Over the past century, intensive research has shown that nordihydroguaiaretic acid and its synthetic analogues have potential use in the treatment of diseases related to cancer, diabetes, bacterial and viral infections, and inflammation.

Tameprocol is a tetra- O -methyl derivative of nordihydroguaiaretic acid [ 33 ]. Nordihydroguaiaretic acid NDGA has anti-inflammatory and antioxidant properties. NGDA treatment after 4 weeks of 2. In previous studies, NDGA has also been reported to extend the lifespan of fruit flies, mosquitoes, and rats.

There have been several studies on the effects of NDGA on brain aging. Nordihydroguaiaretic acid NDGA showed antioxidant and anti-inflammatory activities.

After 4 weeks of administration with 2. This may be related to gender differences as well as drug metabolism. In previous studies, NDGA has also been reported to extend lifespan in Drosophila , mosquitoes, and rats.

There are also some studies on the effects of NDGA on brain aging. In a Drosophila model of Alzheimer's disease, treatment with NDGA extended lifespan, reduced oxidative stress and neuroinflammation, and enhanced memory [ 35 ]. There is also evidence that chronic ingestion of nordihydroguaiaretic acid may cause hepatotoxicity in humans.

Later, NDGA was discontinued as a food preservative when it was shown to be nephrotoxic in rats. Long-term use is associated with hepatotoxicity. In vitro studies showed that NDGA was biotransformed into an active intermediate in vivo, responsible for its toxicity [ 37 ].

Rapamycin Scheme 1 , 5 is a macrolide isolated from Streptomyces hygroscopicus , an actinomycete from soil samples from Easter Island.

Initially rapamycin was discovered as a new antifungal agent, and later it was found to show immunosuppressive and anticancer activity by inhibiting the mechanistic target of rapamycin mTOR [ 38 ].

mTOR forms two distinct protein complexes, mTORC1 and mTORC2; the former is highly sensitive to rapamycin, whereas the latter is only chronically sensitive to rapamycin [ 39 ].

In the last decade, it was evident that genetic and pharmacological inhibition of mTORC1 prolongs lifespan and delays aging, but that inhibition of mTORC2 negatively affects mammalian health and lifespan and leads to many side effects of rapamycin [ 39 ].

In , the TOR pathway was discovered as an important aging regulator in nematodes Caenorhabditis elegans , [ 40 ] and later in yeast Saccharomyces cerevisiae , [ 41 ] and fruit flies Drosphila melanogaster [ 42 ].

Rapamycin was first proposed as a potential anti-aging therapy. Rapamycin supplementation increases median and maximum lifespan in male and female mice.

Results from several independent research groups have shown that rapamycin extends the lifespan of different strains of mice. Beneficial effects have been reported for various treatment strategies, from age of onset i. In mice, rapamycin supplementation improved several age-related indicators such as muscle strength, immune function, oral health, mitochondrial function, coordination and balance, pain perception, cardiovascular disease, and brain health [ 46 , 47 ].

Although many challenges remain in translating the remarkable efficacy of rapamycin therapy into routine clinical practice in age-related diseases, there is no doubt that the future of rapamycin therapy is bright [ 39 ].

Resveratrol Scheme 2 , 2,3,5,4ʹ-trihydroxytrans-stilbene, 6 is a compound of the stilbene family that is a naturally occurring plant polyphenol and a phytoalexin, which was produced when plants are injured or attacked by pathogens.

Resveratrol is mainly found in foods such as grape skins, blueberries, raspberries and mulberries. The cardiovascular health benefits of red wine consumption are due to its high concentration of the non-flavonoid resveratrol [ 50 ] However, after Jang et al.

Since then, many in vitro and in vivo experimental animal studies have found varying degrees of evidence that resveratrol exerts health benefits in a variety of diseases, including cancer, cardiovascular disease, eye disease, and neurodegenerative disorders.

Resveratrol can act in a variety of biological pathways through different mechanisms of action, including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, promotion of survival or angiogenesis. Oxidative stress and inflammation play a key role in the onset and progression of age-related eye diseases such as glaucoma, cataracts, diabetic retinopathy and macular degeneration, leading to progressive loss of vision and blindness [ 50 ].

A recent review discussed the positive effects of resveratrol on longevity, age-related disease, and health maintenance [ 53 ]. Similarly, resveratrol extends the lifespan of nematodes by stimulating SIR It was reported that resveratrol supplementation extended lifespan and delayed age-related motor and cognitive decline in N.

furzeri [ 56 ]. In contrast, resveratrol supplementation had no effect on Daphnia [ 57 ]. Resveratrol improved vascular health without extending the lifespan of mice. While no studies have shown that resveratrol extends life span in healthy mammals [ 58 ]. Potential therapeutic effects of resveratrol in improving ovarian function have also been reported; however, since it also has anti-decidual effects in the endometrium.

Moreover, since its teratogenic potential has not been ruled out, resveratrol should be avoided during the luteal phase and during pregnancy [ 59 ]. The bioavailability of resveratrol showed a high degree of inter-individual variation, not related to age or gender. Despite the low bioavailability of resveratrol, it still acts in vivo.

This may be due to the reconversion of its metabolites from the sulfate and glucuronide of parent resveratrol to resveratrol in target organs, such as the liver. Based on different animal and human studies, nearly 20 resveratrol-derived metabolites have been detected in plasma, urine and some tissues.

Another possible explanation is entero-liver recycling of resveratrol metabolites, which are subsequently broken down and reabsorbed in the small intestine. Based on investigations of the health-related effects of stilbene, the metabolism by human gut microbiota shows significant inter-individual differences.

For years, the prevailing view was that increasing resveratrol intake led to better clearance of reactive oxygen species ROS and, therefore, to cytoprotective effects.

Some studies reported the in vivo toxicity of resveratrol in rats. For example, high doses of resveratrol can cause inflammation of the heart, dilatation of renal tubules, papillary necrosis, acute inflammation of the pelvic area, and death from severe kidney disease.

In addition, high doses of resveratrol could cause significant increases in blood urea nitrogen, creatinine levels, and liver enzymes.

The biological effects of resveratrol, as well as the results in vitro and in vivo, are closely associated to the hormetic effect, with low doses of resveratrol generally associated with beneficial effects and high doses usually having toxic effects [ 61 ]. Although resveratrol has a variety of pharmacological activities, how it leads to different or even completely opposite effects in different diseases remains unclear.

Poor bioavailability of resveratrol is another major drawback of this molecule. The poor bioavailability of this molecule is another of major disadvantage of resveratrol. Sappanone A 7 is an isoflavone isolated from Caesalpinia sappan.

It selectively binds to inosine monophosphate dehydrogenase 2, a protein involved in aging. It has been reported that the life-prolonging and health care effect of sappanone A in Caenorhabditis elegans and its potential pharmacological mechanism were investigated. The larvae were treated with 0—50 μM sappanone A to observe the effects of sappanone A on the longevity of the larvae, and the health status of the larvae was evaluated by measuring the locomotor capacity, feeding capacity, reproductive capacity, heat resistance, lipofuscin content, ROS accumulation, and other indicators.

In addition, the subcellular distribution of GFP labeled DAF was detected, and the interaction between sappanone A and HSP protein was mimicked by molecular docking.

It was found that sappanone A can extend the life span of C. elegans and enhance their motility and heat resistance. Feeding and breeding are not affected. ROS and lipofuscin accumulation decreased. Mechanism studies showed that DAF and HSP gene expression levels were up-regulated. Moreover, DAF is easily located in the nucleus.

In the simulation, sappanone A was docked into the active pocket of the HSP Sappanone A 50 μM can prolong the longevity of C.

elegans and slow down senescence by adjusting the IIS pathway. DAF is particularly crucial in longevity regulation. HSP is joined to enhance the heat tolerance [ 62 ]. Spermidine 8 is the most abundant polyamine in different human tissues, and the concentration of intracellular spermidine decreases during the natural aging process of the body [ 63 ].

Sperm contains high concentrations of spermidine, which prevents cellular senescence and allows long-term survival of the germ cell line. The homeostasis of spermidine is influenced by nutritional intake, intestinal microflora, endogenous biosynthesis, degradation and intercellular transport systems [ 64 ].

High levels of spermidine are found in a wide range of foods, such as fresh peppers, wheat germ, broccoli, cauliflower, and cheeses, while higher levels are found in soy products such as natto, shiitake, and durian [ 65 ].

As a mimetic of caloric restriction, spermidine has significant cardioprotective and neuroprotective effects and activates anti-tumor immunosurveillance in rodent models. In addition, polyamines in diet have been associated with reduced cancer-related and cardiovascular mortality in human epidemiological surveys.

Spermidine maintains mitochondrial function, shows anti-inflammatory activities, and prevents stem cells from aging. Mechanistically, it follows the same biochemical pathway as other caloric restriction mimics: it induces protein deacetylation and relies on autophagy [ 66 ].

Administration of spermidine increased the survival of yeast, nematodes, fruit flies and human immune cells and reduced age-related mortality in mice. In aging flies, spermidine treatment improved memory, an effect associated with increased autophagy in neuronal tissue [ 67 ]. Several studies have been conducted on spermidine treatment in humans.

Long-term spermidine supplementation 1. Food questionnaires have shown that high dietary intake of spermidine lowers blood pressure and benefits cardiovascular disease, while spermidine supplementation 1.

As noted above, spermidine administration increases survival in animal models. A study reportedly aimed to test a potential link between dietary spermidine levels and mortality in humans.

Their findings provide epidemiological support for the concept of spermidine-rich nutrition and improved human survival [ 64 ]. Using the Caenorhabditis elegans model system, the effects of tambulin, a hydroxyl substituted flavanol 3, 5-di hydroxy-7, 8-dimethoxy-2 - 4-methoxy-phenyl chromen4-one, 9 isolated from Zanthoxylum armatum fruits on longevity and neuroregulatory activity were studied.

The results showed that tambulin significantly increased the longevity and stress tolerance of worms, while alleviating the effects of lipofuscin and protein carbonyl on aging biomarkers. Consistent with reduced ROS levels, mRNA expressions of ROS-scavenging genes SOD-1, SOD-3 and CTL-2 were up-regulated after tambulin treatment.

Upregulation of DAF suggests that insulin signaling is involved in tambulin mediated longevity. In conclusion, the relief of PD symptoms mediated by tambulin may be related to the anti-protective mechanism of PD, mainly through up-regulation of mRNA expressions of lagr-1, ymel-1, pdr-1, ubc and lrk Urolithins are a subgroup of 3, 4-benzo coumarin, isolated from the beaver odor gland.

They are found in many microorganisms, plants, human feces and animal feces. In the last decade, research interest in urolithins has increased considerably. The results of studies to date confirm that urolithins can regulate oxidative stress and ameliorate tissue damage through different mechanisms [ 73 ].

Recent reports have shown that urolithin A 10 significantly increases type I collagen expression and decreases matrix metalloproteinase 1 expression. After 20 and 50 μM urolithin A treatment, the expression of collagen mRNA was obviously increased, and the expression of MMP1 mRNA was obviously decreased in a dose-dependent manner [ 74 ].

Urolithins are intestinal metabolites produced by foods rich in ellagitannin such as blackberries, strawberries, pomegranate, tea, walnuts, raspberries, and raspberries. Urolithins have a variety of biological activities, including cardiovascular protection, anti-inflammatory, anti-cancer, anti-diabetic and anti-aging, and have attracted increasing interest in recent years.

Urolithins are involved in a variety of cellular mechanisms, including inhibition of MDM2-p53 interaction, regulation of mitogen-activated protein kinase pathways, and inhibition of NF-κB activity. Anti-aging activity is the most intriguing and perhaps the most important property of urolithin A, which has been intensively studied in recent years due to its unique role in activating mitochondrial autophagy and mitochondrial biogenesis.

Given the importance of mitochondria in the pathophysiology of many diseases, urolithins deserve further in-depth study, especially in clinical trials, to reveal its additional clinical significance.

In addition to the nutritional value of urolithin, recent studies have shown that urolithins can be used as medicines to prevent or treat various diseases. It was reviewed that the potential role of urolithins as novel therapeutic agents, with a special focus on the signaling pathways underlying its biological effects [ 75 ].

Ursolic acid UA, 11 is a usual pentacyclic triterpenoid acid found in apples, prunes, and papaya, as well as in some herbs, and located mainly in waxy coatings, leaves, and bark. UA induces autophagy in a multicellular culture model and in vivo [ 76 , 77 ].

Both in vitro and rodents in vivo studies have shown that UA has anticatabolic activity, counteracts age-related deficiencies in skeletal muscle strength, and quality, and promotes muscle fiber regeneration [ 78 ].

These results support the view that UA can delay aging by increasing the levels of SIRT1 and SIRT6. UA delays or ameliorates aging by boosting anti-aging biomarkers in the hypothalamus. In addition, UA provides suitable conditions for mitochondrial biogenesis and function by promoting PGC-1b overexpression.

P injection to mice twice a day for 7 days. After several treatments, the hypothalamus was isolated from the mice, and the tissue prepared was observed by immunofluorescence microscopy. In addition, UA substantially increased the protein levels of a-Klotho and PGC-1b.

The protein is associated with the metabolism of phosphate, calcium, and vitamin D [ 79 ]. UA leads to the activation of AMPK by reducing cellular energy states ADP and ATP , which causes the up-regulation of SIRT1 expression and thus regulates the transcription of PGC-1α. PGC-1α can promote oxidative metabolism and glycolysis into oxidized fibers, and also promote myoglobin expression and mitochondrial biogenesis.

On the other hand, UA promotes myoblast proliferation by increasing SIRT1 expression in satellite cells [ 80 ]. The longevity extension effect of UA was demonstrated in the nematode model Caenorhabditis elegans [ 81 ]. In WT animals, UA regulates the lifespan of nematodes in a diets-restriction-dependent manner and inhibits the accumulation of toxic proteins by inducing JNK-1 protein aggregation [ 82 ].

The effects of UA on longevity, motor activity and health, including fecundity, intestinal integrity and microbiota composition, of Drosophila melanogaster strain W were investigated.

Phenotypic and molecular target studies showed that UA intake obviously prolonged the lifespan and healthy lifespan of male flies, while female fruit flies did not benefit from UA intake.

In addition, it has recognized roles in antioxidant and genetic induction. Coenzyme Q10 was first synthesized in and was approved for the treatment of congestive heart failure in Japan in Since then, a lot of research has been conducted worldwide on the function and action of coenzyme Q The data confirmed that the compound is safe and effective.

In the United States, coenzyme Q10 has been sold as a dietary supplement under the Dietary Supplement Health and Education Act since [ 84 ]. Long-term administration studies confirmed that this improved bioavailability led to an obvious increase in plasma [ 84 ]. In order to improve the bioavailability of coenzyme Q10, several advances have been made by reducing particle size, enhancing solubility and using new drug carriers [ 87 ].

Solubility can be improved through solid dispersion, prodrug, complexation, ionization, etc. New drug carriers such as liposomes, microspheres, nano-emulsions, nanoparticles and self-emulsifying systems. In a randomized, double-blind, placebo-controlled study, 3 months of administration of a combination of water-soluble coenzyme Q10 50 mg and fish collagen 4.

Other clinical trials have demonstrated the role of water-soluble CoQ10 preparation in the prevention of age-related deafness [ 90 , 91 ]. Recently, the beneficial role of Coenzyme Q10 in aging was reviewed [ 92 , 93 ]. Based on current studies in humans and animals, there are evidence that vitamins A and E may be beneficial for longevity only in the early stages of life, inferring that the production of these benefits may also depend on the presence of an optimal concentration level of them.

To date their mechanisms have not been well established [ 94 ]. Quercetin 13 , caffeic acid 14 and rosmarinic acid 15 can induce hormetic dose-responsive to prolong life span in Caenorhabditis elegans. The three polyphenols showed different antioxidant properties in vivo, indicating different modes of action Scheme 3.

elegans is apparently able to recognize these polyphenols and activate immune response pathways. They do not lead to an indirect dietary restriction effect that prolongs life, but they do cause substantial energy redistribution.

These findings highlight the diverse actions of polyphenols in vivo and demonstrate that they can target aging process in whole life, not just improve survival in old age [ 95 ].

Quercetin μM was found to have a moderate effect on growth, while DMSO as a control had no effect on longevity or growth rate. In Podospora anserina WT treatment, the mean life expectancy increased by In normal culture, the presence of genistein 16 significantly extended the longevity of nematodes.

Furthermore, genistein enhances the survival rate of nematodes under thermal and oxidative stress conditions. Further studies exhibited that the enhanced stress resistance of C.

elegans mediated by genistein may be related to the enhanced expression of superoxide dismutase SOD-3 and heat shock protein HSP In addition, no significant changes in aging-related factors induced by genistein were observed.

The usual aging-related factors includes reproduction, food intake, and growth. It suggests that the life span extension activity of genistein was not associated with these factors.

Genistein can also up-regulate the motility of aged nematodes, indicating that genistein can affect the healthspan and longevity of nematodes.

The results showed that genistein had beneficial effects on the longevity of nematodes under normal and stress conditions by increasing the expression of anti-stress proteins [ 97 ].

However, the evidence was given for a new biotransformation pathway in C. elegans that leads to the derivatives formation of glucoside and glucoside phosphate, which so far have not been found in mammals.

Therefore, there are huge differences in the metabolism of genistein in mammals and nematodes, which may have a great influence on their biological activity. The differences need to be properly considered when C.

elegans is used as a model to evaluate possible health or aging effects [ 98 ]. Green tea has been found to prolong the life span of different animal models.

In male mice, it was found that green tea administrating mice lived longer than mice of control group. EGCG significantly extended the median life span of the rats to weeks. One study reported that EGCG delayed death in healthy rats and reduced its age-related oxidative stress, inflammation, and liver and kidney damage [ ].

Further studies showed that the significant life span extending effects of EGCG on nematodes could be attributed to its free radical scavenging effect in vitro and in vivo and its upregulation of SOD-3 and HSP The gender-specific effect of green tea on the life span of Drosophila melanogaster was studied and it was reported that green tea could only prolong the life span of male flies.

This effect was found to be independent of typical aging interventions such as calorie restriction, regulation of oxidative energy metabolism and increased tolerance to stress.

The results suggest that green tea prolongs the longevity of male fruit flies by reducing their reproductive potential, possibly by restricting iron intake [ ]. The average life expectancy of EGCG increased by Under oxidative stress, EGCG increased the average lifespan of nematodes by EGCG could not prolong the longevity of nematodes under common culture conditions.

Protandim Prot is a mixture of five plant extracts. The five extracts contain bacosides, curcumin, epigallocatechingallate, silymarin, and withaferin A. Biochemical and histological surveys in mice showed that Prot administration inhibited oxidative stress, cell proliferation, and tumor promoter-induced inflammation.

In addition, Prot treatment has been reported to protect the heart from oxidative stress and fibrosis in a rodent model of pulmonary arterial hypertension. In a follow-up study, only male mice were found to show a positive effect of Prot in life span extension.

Another compound, chicory acid 18 , CA , has been found to increase insulin secretion and glucose uptake in INS-1 and L6 cell lines, respectively. Concentration-dependent longevity was observed in CA.

The data suggest that CA is a potent antioxidant that activates the AMPK pathway in the L6 myotubes. Similar to other AMPK activators, CA extends the lifespan of nematodes, an effect that can be measured even in the micromolar range [ ].

Tyrosol 19 is a lipid-soluble phenol isolated from olive leaves and extra virgin olive oil. The results show that important molecular mechanisms directly associated with longevity are affected by tyrosol treatment in nematodes, suggesting that this molecule may play an important role in conserved genetic pathways to extend the longevity of the entire organism [ ].

Fisetin is a highly fat soluble compound that easily crosses cell membranes and is assembled inside cells. This allows fisetin to have diverse beneficial effects, including anti-inflammatory, neuroprotective, anticancer and anti-diabetic effects.

Fisetin was found to be a promising analogue of caloric restriction, effectively maintaining redox homeostasis during rat erythrocyte senescence.

In addition, fisetin administration effectively reduces the excretion process associated with aging [ ]. Fisetin is a potent compound in reducing aging markers in mouse embryonic fibroblast senescence induced by oxidative stress and human fibroblast senescence induced by the genotoxin etoposide.

Fisetin also decreased markers of aging in aged mice, and in human adipose tissue explants. Fisetin treatment increased health and longevity in WT mice and aged mice [ ]. Senolytics fisetin and dasatinib plus quercetin have been shown to extend the lives of mice [ ].

Telomere activator TA , also known as cycloastragenol 21 , is a potent small-molecule telomerase activator with the ability to extend telomeres length, which is purified from the plant Astragalus membranaceus [ ].

Since , it has been commercially marketed as a nutritional product that increases the average telomere length of haploinsufficient mouse embryonic fibroblasts MEFs and reduces the percentage of very short telomeres and DNA damage [ ].

In a 1-year double-blind clinical trial, 38 patients were randomized into two groups, one with oral TA for intervention and the other with placebo as a control. The macular function was measured by micro-perimetry as the primary index.

Compared with the control group, oral TA significantly improved the macular function of patients [ ]. In order to study the anti-aging effect of PC on C. elegans , C. This is especially important as you get older and your skin becomes drier, which makes it more prone to wrinkles. Research shows that using a moisturizer that contains hyaluronic acid and vitamin C are especially effective at preventing wrinkles from forming or getting deeper.

Drinking water is essential for good health. Your body needs water for almost every function it does. Besides vital functions like flushing toxins from your body, aiding with digestion, and regulating your body temperature, water can also help keep your skin healthy and hydrated from the inside.

According to a study that was conducted on a healthy group of women, it was determined that higher water input can have an effect on the hydration of the skin, and it may positively affect skin physiology.

A large Dutch study from that had more than 2, participants found that dietary habits are associated with facial wrinkling, especially in women.

According to the study, women whose diets include a high amount of red meat and unhealthy snacks tend to have more facial wrinkles than women who include more fruit in their diet. Some foods and drinks with these qualities include:. According to a study , your sleeping position may have an effect on the formation of wrinkles.

The study found that people who sleep on their side or stomach are prone to mechanical compression forces, which can speed up the formation of wrinkles, and also distort facial skin. Silk pillowcases may also be kinder to your skin than cotton, as they create less friction and help prevent abrasion of the skin.

Tobacco smoke damages collagen and elastin, the fibers that give your skin its elasticity and strength. Also, the nicotine in cigarettes causes your blood vessels to constrict. This reduces the blood flow to your skin. According to the Mayo Clinic , the heat associated with cigarettes may also cause wrinkles.

Additionally, the repeated pursing of the lips to inhale may lead to premature wrinkling around the mouth. If you currently smoke, talk to your healthcare provider about a smoking cessation program to help you quit.

Repeated facial movements like squinting, frowning, or pursing of the lips can speed up the formation of wrinkles. If you find yourself squinting frequently, it may be a sign that you need to get your eyes checked or that you need a stronger prescription for your glasses or contact lenses.

Getting a new prescription may benefit your skin as well as your eyes. If you find yourself frowning or scowling often, you may want to look into ways to relieve your stress.

Some helpful stress management techniques include:. Wrinkles are an inevitable part of aging, but there are steps you can take to slow their progress and prevent new ones from forming.

Lifestyle factors like eating a vitamin-rich diet, drinking plenty of water, protecting your skin from the sun, not smoking, and managing your stress play a key role when it comes to keeping your skin healthy and youthful.

Using a retinoid and a moisturizer that contains hyaluronic acid and vitamin C can also be effective at preventing the onset of wrinkles. If you have questions or concerns about products that may help prevent wrinkles, be sure to follow up with your doctor or dermatologist.

The active ingredients in skincare products can be divided into preventative, therapeutic, and specialty.

Preventative ingredients are those, like topical antioxidants, that are best-used long-term to prevent skin aging. Therapeutic ingredients, like retinoids, alpha hydroxy acids, vitamin C, and some peptides, can repair existing damage.

Many therapeutic ingredients can also help slow down aging changes in the future. Specialty ingredients like salicylic acid, benzoyl peroxide, and tea tree oil for acne; or arbutin, soy, licorice, and bearberry for hyperpigmentation.

Pick a skincare program with preventative and therapeutic components and a specialty component if needed. Some aging is genetic. Facial muscle structure and characteristic facial expressions tend to run in families. Unless you start with Botox early before the lines are etched. Some people inherit skin that loses elasticity earlier than average.

There are strategies to reduce the influence of these genetic tendencies and to treat them early with non-invasive treatments. If Botox or filler treatments are indicated, they may prevent worse lines from forming later on.

Light chemical peels treat acne and pigmentation, helping to prevent areas that may scar. Be proactive, make the right choices, and look great at all ages. Youth, health, and the ability to change the course of skin aging are gifts. Like the other choices in your twenties regarding education, your love life, kids, and lifestyle, do your best to choose wisely.

If you make the wrong choice, stop, re-evaluate, learn from your mistakes, change course, and move ahead. It is all part of the total life experience. Receive news, updates and special notes from Dr. Get directions. Free Shipping.

Every Day! Vice is Not Nice To Your Skin Smoking cigarettes reduces blood flow in the skin and exposes you to direct toxin exposure on the skin and in the blood. Retinoids Are Worth It Start using a retinoid daily in your twenties.

Acne is a Bummer Adult acne is extremely frustrating. Scars Are Forever Scarring from picking or from the acne itself looks worse the older you get, as the skin loses elasticity and the scars become more sunken in and more obvious.

Start an Active Skin Care Program Combined with daily sunscreen and a daily retinoid, get into the habit of using an active skincare line and start early. A Hydroxy Acid-- Salicylic acid if you have acne. For anti-aging, use an alpha-hydroxy glycolic acid or multi-fruit acid.

If you have acne and want anti-aging help too, then use both salicylic acid and an alpha-hydroxy glycolic acid or multi-fruit acid unless your skin is too dry or sensitive to tolerate it. Pick a couple of antioxidants from the following list.

Antioxidants in many fruits and plants, vitamins, or produced in the lab bind to skin-damaging free radicals released by environmental exposure to UV light, pollution, cigarette smoke, and various toxins, rendering them harmless.