Dr. James Manos (MD)
July 5, 2019
July 5, 2019
During their investigation of longevity-promoting natural products and Chinese herbs in the last 15 years, the authors of a study concluded that to have healthy, productive, and graceful maturing, it is necessary to maintain a dynamic balance between pro-inflammatory and anti-inflammatory loads. This may also help prevent cancer and premature degeneration of various organ systems. Modern lifestyle and food intake tend to overload pro-inflammatory factors. To overcome this, it is desirable to regularly consume fresh fruits, vegetables, various grains, various beans, including soybeans, and/or minimally processed, unbleached products. When this is not sufficient or possible, taking proper dietary supplements under the guidance of knowledgeable health professionals can be helpful (26).
Aging is a universal biological process that leads to progressive and deleterious changes in organisms. Since ancient times, mankind has been interested in preventing and keeping ourselves young. Nowadays, the meaning of anti-aging has been changed from merely prolonging lifespan to increasing health span, which emphasizes the quality of life. This is the concept of healthy aging and preventing pathological aging associated with diseases. Keeping our brain functions at an early age is essential for neuroscientists to prevent aging-associated neurological disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Herbal medicine has a long history in Asian countries. It is believed that many medicinal herbs have anti-aging properties. Recent studies have shown that some medicinal herbs are useful in the intervention or prevention of aging-associated neurological disorders. In a review, the authors used wolfberry and ginseng as examples to elaborate on the properties of anti-aging herbs. The characteristics of medicinal herbs, especially their applications in different disease stages (prevention and intervention) and multi-target properties, allow them to be potential anti-aging interventions in the prevention and treatment of aging-associated neurological disorders (27).
Resveratrol, a compound commonly found in red wine, has attracted much attention recently. It is a diphenolic natural product accumulated in grapes and a few other species under stress conditions. It possesses an exceptional ability to increase the lifespan of eukaryotic organisms, ranging from yeast to fruit flies to obese mice (8).
Other substances that may increase longevity are astragalus (however, it is still under investigation), grapefruit, cranberry juice (it has the more significant amounts of the antioxidants polyphenols), melatonin (it is also an antioxidant; however, it is not recommended for prolonged use – more than 3 months), holy basil (Ocimum tenuiflorum, or Tulsi)(longevity properties have not been proved yet), saffron (it is said that Krokus from the Greek region of Kozani, organic red saffron, has the most potent activity), garlic (especially aged garlic extract, known as Kyolic (R)), black tea, blueberries, royal jelly, cinnamon bark, Panax ginseng, Rhodiola, carnosine and coenzyme Q10.
Polyphenols are the most abundant antioxidants found in food. They are known to have a protective effect against cardiovascular diseases and cancers, and there is some evidence of neuroprotective effects. Sinclair et al examined a set of plant polyphenols for their effect on Sirt1 catalytic rate. These sirtuin-activating compounds (STACs) included butein, piceatannol, fisetin, quercetin, and resveratrol (21).
A study further tested the potential effects of six other longevity-promoting compounds on induced pluripotent stem cells (iPSCs) induction, including two sirtuin activators (resveratrol and fisetin), an autophagy inducer (spermidine), a PI3K (phosphoinositide 3-kinase) inhibitor (LY294002), an antioxidant (curcumin), and an activating adenosine monophosphate-activated protein kinase activator (metformin). All these chemicals promoted somatic cell reprogramming except for metformin, though to different extents. The results show that the controllers of somatic cell reprogramming and organismal lifespan share some common regulatory pathways, which suggests a novel approach to studying aging and longevity based on the regulation of cellular reprogramming (22).
In Drosophila melanogaster (fruit fly), in the wild-type strain Canton-S, lifespan was extended up to 23% with fisetin and up to 29% with resveratrol. A calorie-restricted diet increased fly lifespan by 40% in females and 14% in males. Under these conditions, neither fisetin nor resveratrol further increased longevity, indicating that caloric restriction and resveratrol administration regulate a common genetic program controlling aging. Resveratrol failed to extend lifespan in flies completely lacking functional Sir2 or in flies in which Sir2 is severely decreased. An independent investigation confirmed resveratrol's lifespan-promoting properties appeared, but a different study disputes this notion (23).
Flavonoids in many herbal edibles possess a remarkable spectrum of biochemical and pharmacological actions and are assumed to exert beneficial effects on human health. A study used the multicellular model organism nematode Caenorhabditis elegans which is conserved in molecular and cellular pathways to mammals, to examine the results of the flavonoids kaempferol and fisetin concerning their protective action in individual living worms. Both flavonoids increased the survival of C. elegans, reduced the intracellular reactive oxygen species (ROS) accumulation at lethal thermal stress, and diminished the extent of induced oxidative stress, with kaempferol having a stronger impact. Kaempferol, but not fisetin, attenuated the gathering of the aging marker lipofuscin suggesting a life-prolonging activity of this flavonoid. In addition to these effects that may be attributed to their potential antioxidant, kaempferol, and fisetin caused translocation of the C. elegans FoxO transcription factor DAF-16 from the cytosol to the nucleus indicating a modulatory influence of both flavonoids on signaling cascade(s) (24).
A study published on 6 October 2010 in the journal ‘‘Cell Metabolism’’ revealed that branched-chain amino acids (BCAAs) supplementation, especially the amino acids leucine, isoleucine, and valine, not only increases energy and stamina (power) but also may lengthen lifespan and offer longevity. Branched-chain amino acids (BCAAs) have been shown to extend the chronological life span in yeast. The study showed that a BCAA-enriched mixture (BCAAem) increased the average lifespan of mice. BCAAem supplementation increased mitochondrial biogenesis and sirtuin 1 expression in primary cardiac and skeletal myocytes and cardiac and skeletal muscle but not in the adipose (fat) tissue and liver of middle-aged mice. This was accompanied by enhanced physical endurance. Also, the reactive oxygen species (ROS) defense system genes were upregulated, and ROS production was reduced by BCAAem supplementation. All BCAAem-mediated effects were strongly attenuated in endothelial nitric oxide (NO) synthase null mutant mice. The study concluded the critical anti-aging role of BCAAs is mediated by mitochondrial biogenesis in mammals (1), (2), (3).
Another study showed that Cinnamon Bark and Ginseng in Herbal Formulas increase the life span of Roundworms. Specifically, researchers at the University of Maryland, Baltimore, used the roundworm Caenorhabditis elegans (C. elegans) which has some genetic and biochemical similarities to humans, to examine complicated herbal preparations to combat the adverse effects of aging. The above worms have a brief lifespan (about 20 days). In an NCCAM-funded study, researchers assessed two traditional Chinese multi-herbal formulas—Huo Luo Xiao Ling Dan (HLXL), taken for chronic inflammatory pain (e.g., joint pain from arthritis); and Shi Quan Da Bu Tang (SQDB), considered to reduce fatigue and improve general wellness. They found that cinnamon bark, a component of both formulas, increased the worms’ lifespan. Of all the individual ingredients tested, only two significantly prolonged life spans: Cinnamomum cassia bark (present in both recipes) and Panax ginseng root (present in SQDB only) (4).
In a study, two commonly used traditional herbal formulas, Shi Quan Da Bu Tang (SQDB) and Huo Luo Xiao Ling Dan (HLXL), were evaluated using a survival assay and oxidative stress biomarkers in a well-established roundworm Caenorhabditis elegans (C. elegans) model of aging. HLXL is an eleven-herb formula modified from a top-selling traditional herbal recipe for the treatment of arthritic joint pain. SQDB consists of ten herbs often used for fatigue and energy, particularly in the aged. The authors demonstrated that SQDB significantly extends lifespan in a C. elegans model of aging. Among all individual herbs tested, two herbs Cinnamomum cassia bark (Chinese pharmaceutical name: Cinnamomi Cortex, CIN) and Panax ginseng root (Chinese pharmaceutical name: Ginseng Radix, GS), significantly extended lifespan in C. elegans. CIN in both SQDB and HLXL formulas extended lifespan via modulation of multiple longevity assurance genes, including genes involved in insulin signaling and stress response pathways. All the life-span-extending herbs (SQDB, CIN, and GS) also attenuated levels of H2O2 and enhanced small heat shock protein expression. Also, the lifespan-extending herbs significantly delayed human amyloid-beta (Abeta)-induced toxicity in transgenic C. elegans expressing human Abeta (note from the writer of this review: that implies that they may prevent Alzheimer’s disease) (33).
Lycium barbarum (Gouqizi, Fructus Lycii, Wolfberry, Goji berry) nourishes the liver and improves eyesight. However, many people have forgotten its anti-aging properties. Valuable components of L. barbarum are not limited to its colored elements containing zeaxanthin and carotene. Still, they include polysaccharides and small molecules such as betaine, cerebroside, beta-sitosterol, p-coumaric, and various vitamins. Even though L. barbarum has been used for centuries, but its beneficial effects on our bodies have not been comprehensively studied. The authors' laboratory recently demonstrated neuroprotective impacts to counter the neuronal loss in neurodegenerative diseases. Polysaccharides extracted from L. barbarum can protect neurons against beta-amyloid peptide toxicity in neuronal cell cultures and retinal ganglion cells in an experimental model of glaucoma. They have even isolated polysaccharides' active component, which can attenuate stress kinases and pro-apoptotic signaling pathways. Also, the authors have accumulated scientific evidence for its anti-aging effects that should be highlighted for modern preventive medicine (30).
PaMTH1is an O-methyltransferase catalyzing the methylation of vicinal hydroxyl groups of polyphenols. O-methylation is performed by O-methyltransferases which are members of the S-adenosylmethionine (SAM)-dependent O-methyltransferase superfamily involved in the secondary metabolism of many species across all kingdoms. Deletion of PaMth1 was found to lead to a decreased resistance against exogenous oxidative stress and to a shortened lifespan suggesting a role of PaMTH1 as a longevity assurance factor in a new molecular pathway involved in lifespan control (6).
In the budding yeast Saccharomyces cerevisiae, lifespan extension by calorie restriction requires the NAD1-dependent histone deacetylase, Sir2. It has been recently shown that Sir2 and its closest human homolog SIRT1, a p53 deacetylase, are strongly inhibited by the vitamin B3 precursor nicotinamide. A study showed that increased expression of PNC1 (pyrazinamidase/ nicotinamidase 1), which encodes an enzyme that deaminates nicotinamide, is necessary and sufficient for lifespan extension by calorie restriction and low-intensity stress. PNC1, in the study, is identified as a longevity gene responsive to all stimuli that extend lifespan. The study showed that nicotinamide depletion is sufficient to activate Sir2 and that this is the mechanism by which PNC1 regulates longevity. The study concluded that yeast lifespan extension by calorie restriction is the consequence of an active cellular response to low-intensity stress and speculated that nicotinamide might regulate critical cellular processes in higher organisms (7).
Rhodiola is a plant root used in traditional Chinese medicine that may increase an organism's resistance to stress. It has been proposed that Rhodiola can extend longevity and improve health by alleviating oxidative stress. In a study, Rhodiola was supplied every other day at 30 mg/mL significantly increased the lifespan of Drosophila melanogaster (fruit fly). When comparing the distribution of deaths between Rhodiola-supplemented and control flies, Rhodiola-fed flies exhibited decelerated aging (9).
Panax ginseng is a well-known medicinal herb in North America and Europe. A study investigated the association between ginseng intake and mortality among members of the Korean population. The study examined 6,282 subjects who were 55 or older. The 18.8-year progressive cohort study concluded that ginseng intake decreased all-cause mortality in older males, but such a life prolongation effect was not shown in women (10).
Aging results from complex genetically and epigenetically programmed processes elicited partly by noxious or stressful events that cause apoptosis (programmed cell death). A study reported that the administration of spermidine, a natural polyamine whose intracellular concentration declines during human aging, markedly extended the lifespan of yeast, flies, worms, and human immune cells. Also, spermidine administration potently inhibited oxidative stress in aging mice. The study found that enhanced autophagy (the degradation of the cell’s components through the lysosomal machinery) is crucial for the polyamine-induced suppression of necrosis and enhanced longevity (12).
Another study found that reducing the concentration of polyamines (spermine, spermidine, and putrescine) in the body pool may slow the cancer process. Because dietary spermine, spermidine, and putrescine contribute to the body pool of polyamines, quantifying them in the diet is essential. The foods from the evaluated database were fresh and frozen corn. Orange and grapefruit juices contributed the highest amount of putrescine (44,441 nmol/day) to the diet. Green peas contributed the highest amount of spermidine (3,283 nmol/day), and ground meat added the highest amount of spermine (2,186 nmol/day) (11).
CBA, SHR, HER-2/neu, and SAM mice revealed inhibition of age-related alterations in estrus function and spontaneous tumor development and showed lifespan extension under the influence of the pineal gland hormone Melatonin, synthetic peptide bioregulator Epitalon, delta-sleep-inducing peptide Deltaran, enterosorbent Aqualen, and succinic acid-containing preparation Neuronol (Noogam) (15).
From the age of 3 months until their natural deaths, female outbred Swiss-derived SHR mice were subcutaneously injected on 5 consecutive days every month with 0.1 ml of normal saline (control) or with 1.0 microg/mouse (approximately 30 – 40 microg/kg) of tetrapeptide Epitalon (Ala-Glu-Asp-Gly) dissolved in 0.1 ml saline. There were 54 mice in each group. This study showed that treatment with Epitalon did not influence food consumption, body weight, or the mean lifespan of mice. However, it increased by 13.3% the lifespan of the last 10% of the survivors and by 12.3% the maximum lifespan in comparison with the control group. Also, it was demonstrated that treatment with Epitalon did not influence total spontaneous tumor incidence but inhibited the development of leukemia (6.0-fold) compared to the control group. The study suggests a geroprotector (that prevents the consequences of aging) activity of Epitalon and the safety of its long-term administration in mice (16).
Female SHR mice were fed the activated carbon fiber adsorbent Aqualen beginning at the age of 3 months through their life. The mice were fed Aqualen five times per week together with lab chow at a daily dose of 100 mg/kg b.w. The results showed that the addition of Aqualen into food did not significantly influence the dynamics of body weight and the mean lifespan of the animals. At the same time, the age at 90% mortality of mice was 4 months longer in the group exposed to Aqualen. There were no statistically significant differences in the incidence of all tumors and malignant tumors in the mice treated with Aqualen, compared to the control group. However, in the group of mice exposed to Aqualen, there was a 1.4 times reduction in the mean number of tumors per mouse. It could be supposed that Aqualen has some geroprotective (that prevents the consequences of aging) and anticarcinogenic properties (17).
In a study, treatment of female SAMP-1 mice with Neuronol (a drug containing succinic acid) given with drinking water starting at 2 months old during the whole life prolonged the lifespan. It markedly reduced the mortality of animals aged 1.5 – 2 years. Neuronol inhibited the development of spontaneous tumors, primarily lymphomas, and significantly prolonged lifespan in mice with tumors. Long-term treatment with Neuronol had no pathological (harming) side effects. The experiments demonstrated geroprotective (that prevents the consequences of aging) and anticarcinogenic activity of Neuronol and the safety of its long-term use (18).
A study investigated whether Vigconic 28 (VI-28), a Yang-invigorating Chinese herbal formula, could affect the survival of aging animals. Male and female C57BL/6J mice were given a VI-28-supplemented diet starting at 36 weeks of age until death. The results showed that VI-28 dietary supplementation at 0.05% significantly increased the median lifespans of both male and female mice compared to controls. Survival enhancement was associated with protection against age-associated impairments in mitochondrial antioxidant status and functional ability in various tissues. In conclusion, VI-28 could retard the aging process in mice, probably by mitigating age-associated declines in mitochondrial antioxidant status and functional capacity in tissues (25).
A study investigated the effect of Tiao – Geng – Tang (TG-decoction), a Chinese herbal mixture extract, in balancing female hormones, regulating the expression of estrogen receptors (ERs), and preventing aging-related tissue damage. In the study, ovariectomized (with the ovaries surgically removed) 5-month-old female rats were used to model menopause and treated with either TG-decoction or conjugated estrogen for 8 weeks. The study concluded that the TG-decoction balances female hormones similarly to conjugated estrogens but less effectively. However, it is superior in up-regulating ERα and β and exhibits antioxidant & antiaging activities. While it shares similar effects with estrogen, TG-decoction also seems to have unique and more complex functions and activities (28).
In Chinese, the name Lingzhi represents a combination of spiritual potency and the essence of immortality. It is regarded as the ΄΄herb of spiritual potency΄΄, symbolizing success, well-being, divine power, and longevity. Among cultivated mushrooms, Ganoderma lucidum (Lingzhi or Reishi) is unique in that its pharmaceutical rather than nutritional value is paramount. Commercial G. lucidum products are available in various forms, such as powders, dietary supplements, and tea. The specific applications and attributed health benefits of lingzhi include control of blood glucose levels, modulation of the immune system, hepatoprotection (protection of the liver from damage, e.g., from toxins), bacteriostasis, and more. The various beliefs regarding the health benefits of G. lucidum are based mostly on anecdotal evidence, traditional use, and cultural mores. However, recent reports provide scientific support to some of the ancient claims of the health benefits of Lingzhi (32).
Skin aging
The association between Ayurveda and anti-aging is gaining importance in beauty, health, and wellness. Ayurvedic cosmeceuticals date back to the Indus Valley Civilization. Modern research trends mainly revolve around principles of the anti-aging activity described in Ayurveda: Vayasthapana (age-defying), Varnya (brighten skin-glow), Sandhaniya (cell regeneration), Vranaropana (healing), Tvachya (nurturing), Shothahara (anti-inflammatory), Tvachagnivardhani (strengthening skin metabolism) and Tvagrasayana (retarding aging). Many rasayana plants, such as Emblica officinalis (Amla) and Centella asiatica (Gotu kola) are extensively used (29).
Phytoconstituents are gaining popularity as ingredients in cosmetic formulations as they can protect the skin against exogenous and endogenous harmful agents and help with skin conditions. Exposure of skin to sunlight and other atmospheric conditions causes the production of reactive oxygen species, which can react with DNA, proteins, and fatty acids, causing oxidative damage and impairment of the antioxidant system. Such injuries damage regulation pathways of the skin and lead to photoaging (skin aging from sunlight exposure) and skin cancer development. The effects of aging include wrinkles, roughness, the appearance of fine lines, lack of elasticity, and de- or hyperpigmentation marks. Herbal extracts act on these areas, producing healing, softening, rejuvenating, and sunscreen effects. The authors selected a few photoprotective phytoconstituents, such as curcumin, resveratrol, tea polyphenols, silymarin, quercetin, and ascorbic acid. They discussed the considerations to be undertaken for the development of herbal cosmetic formulations that could reduce the occurrence of skin cancer and delay the process of photoaging (31).
About palmistry and lifespan
About sleep and lifespan
Most people sleep 7 – 8 h (hours) per night. If someone is deprived of sleep, his/her performance suffers greatly; however, a few do well with just 3 – 4 hours of sleep–a trait that seems to run in families. Determining which genes underlie this phenotype could shed light on the mechanisms and functions of sleep. A study performed mutagenesis in Drosophila melanogaster (fruit fly) because flies also sleep for many hours and, when sleep-deprived, show sleep rebound and performance impairments. It was demonstrated that short-sleeping Shaker flies have a reduced lifespan. Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency (19).
Based on data for 53 mammalian species reported in the literature, statistical analyses revealed that daily sleep quotas correlate positively with metabolic rate and negatively with maximum lifespan and brain weight. Sleep cycle length correlates positively with lifespan and brain weight and negatively with metabolic rate. The correlation between sleep time and metabolic rate suggests that sleep enforces rest and limits metabolic requirements, although some inconsistent findings are noted. Strong relationships between cycle length with brain weight and metabolic rate suggest that the significance of cycle length has not been sufficiently explored (14).
In a study, female SHR mice received 5-day long monthly courses of delta-sleep-inducing peptide (DSIP) preparation ‘Deltaran (R)’ subcutaneously in a 5 mg/kg dose during all their lives. It was demonstrated that the last 10% (most aged) of mice that received Deltaran lived for 16% longer than the controls. They had significantly higher vertical activity in the ‘open field’ test than the controls, starting from 6 months old until their natural death. Also, Deltaran slowed the spontaneous carcinogenesis (cancer development) parameters. It is assumed that DSIP preparation Deltaran has geroprotective (that prevents the consequences of aging), anxiolytic (controls anxiety), and antitumor activity (13).
The hypothesis that melatonin supplementation can increase the lifespan of a single-celled organism was tested by the administration of melatonin to the ciliated protozoan Paramecium tetraurelia, an aerobic, single-celled organism. Melatonin supplementation in dim red light at a dose of 0.043 mM (10 mg/L) of nutrient media (bacterized Cerophyl) per day, followed by incubation for 23 hours in darkness, increased the mean clonal lifespan of Paramecium tetraurelia in days by percentages ranging from 20.8% to 24.2% over controls. Maximum clonal lifespan in days was also raised in melatonin-supplemented cells, from 14.8% to 24.0% over controls. The finding that melatonin supplementation increased clonal lifespan in Paramecium tetraurelia, an aerobic, single-celled organism, suggests that the mechanism of melatonin’s longevity-promoting effects may be intracellular (20).
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