Summer is Here … Protect Your Skin from the Inside Out

Summer is Here ... Protect Your Skin from the Inside OutExcessive sun exposure can lead to premature aging of the skin; which means more wrinkles and discolorations. Although topical sunscreens remain the top choice of consumers, there is a new oral method for protecting your skin … Polypodium leucotomos.

Much has been written about how the sun’s burning ultraviolet rays harm our health and appearance. Yet despite the warnings, more than two million people in the US will be diagnosed with skin cancer this year alone. Rates of melanoma — the most dangerous form of skin cancer — have not only doubled over the past 10-20 years, but continue to rise 3% to 7% annually.1

A recent study found that a new oral supplement sourced from the fern, Polypodium leucotomos, could potentially become an important anti-aging ingredient for the skin.2  Extracts from the fern have been used in South America for many years to protect against the damaging effects caused by excessive sun exposure.

This amazing fern also protects skin cells from the consequences of excessive ultraviolet radiation by reducing sun-induced injury.3 Additionally, it helps ease skin inflammation and blocks protein-destroying skin enzymes.3,4

Polypodium leucotomos extract also contains a high percentage of potent antioxidants (phenolics) which block the formation of dangerous free radicals and the oxidative damage that results from excessive sun exposure.5

Remember, for long periods of sun exposure, you should defend your skin against premature aging with an oral extract from Polypodium leucotomos and a topical sunscreen to ensure complete sun protection.


  1. Available at: Accessed May 3, 2010.
  2. Philips N, Conte J, Chen YJ, et al. Beneficial regulation of matrixmetalloproteinases and their inhibitors, fibrillar collagens and transforming growth factor-beta by Polypodium leucotomos, directly or in dermal fibroblasts, ultraviolet radiated fibroblasts, and melanoma cells. Arch Dermatol Res. 2009 Aug;301(7):487-95.
  3. J Photochem Photobiol B. 2006 Mar 1;82(3):173-9.
  4. J Dermatol Sci. 2003 Jun;32(1):1-9.
  5. Ann Intern Med. 1971 Dec;75(6):873-80.

Stress, Immortality, and the Hormesis Hypothesis

Stress, Immortality, and the Hormesis Hypothesis

By Steven V. Joyal, MD

Stress, Immortality, and the Hormesis HypothesisIs low-level stress the secret to immortality?

Longevity scientists have long been puzzled by the fact that stress, when carefully applied, very often results in prolongation of lifespan rather than causing premature death.

We need to be careful by the manner in which we characterize or define stress in the context of lifespan extension. Stress, as a critical causal factor in lifespan extension, is best defined by the term hormesis. When stress, either internal or external, is applied to a living system at a relatively low level so that a beneficial biological adaptation occurs, we define this as hormesis. The capacity of a biological system to adapt and thrive in response to stress is critical to survival. In fact, aging itself can be characterized as the inability to adapt and respond successfully to stress.

We must differentiate chronic stress that overwhelms a biological system and results in damage and decay from the type of low-level stress of hormesis that contributes to a beneficial biological response. For example, chronic stress that causes large bursts of the hormones cortisol and “fight or flight” catecholamines like adrenaline accelerates the aging process and reduces lifespan. In contrast, low-dose radiation with gamma rays and beta radiation has been shown in several studies to stimulate natural chemical and biological processes that are actually protective against cancer.1-4 This may seem surprising to some, but low-level gamma radiation, rather than causing cancer and premature death, has been shown to suppress cancer induction from chemical carcinogens, oncogenic retroviruses, and viral oncogenes like ras and src.5,6

Significant lifespan extension as a result of calorie restriction is probably the best evidence in support of the hormesis hypothesis as applied to longevity. Animals that are calorie restricted are able to significantly suppress chemical and radiation-induced cancers as opposed to peer controls fed ad libitum. Calorie restriction in animals results in an increase in resistance to oxidative stress and the negative effects of excess inflammation as well as the deleterious impact of exhaustive physical exercise.

The beneficial biological response to oxidative stress in calorie restriction is particularly impressive. Animals under calorie restriction have reduced levels of oxidatively damaged proteins, lipids, and DNA. Calorie restricted animals have an amazing capacity to beneficially modify gene expression involved in glucose metabolism, protein synthesis, and cellular energy capacity. Gene expression in calorie restricted animals shows adaptations involving enhancement of detoxification, anti-inflammatory pathways, and DNA repair enzymes.

Do the impressive adaptive benefits of calorie restriction share a common pathway?

The hormesis hypothesis helps provide an answer.

The mild stress of calorie restriction rapidly turns on a variety of gene pathways critical for essential defense and survival of the organism. Gene expression studies show that calorie restricted animals rapidly turn on genes related to stress response and energy metabolism. For example, Lee et al showed that of 6,437 genes activated by calorie restriction, nearly 30% were related to energy metabolism and stress response.7 Hormesis as an explanation for the biological benefits of calorie restriction implies an adaptive mechanism through evolutionary biology. In order to survive, living systems must adapt to an ever-changing barrage of internal and external insults. The low-level stress of calorie restriction produces gene expression changes that create a variety of positive adaptive responses for longevity.

In addition to calorie restriction, other strategies may help mimic the hormetic response. Consistent, mild-to-moderate (never exhaustive) exercise triggers a variety of adaptive mechanisms similar to calorie restriction. Exercise adaptation includes improvements in insulin signaling, mitochondrial energy metabolism, and resistance to oxidative stress, all of which are also known to occur with calorie restriction.

Nutrients, too, have hormetic properties. One example is vitamin D. The past decade has seen a veritable explosion of research supporting beneficial biological roles for vitamin D in the immune system, cardiovascular system, central nervous system, and endocrine system, in addition to control of the cell cycle and cancer pathogenesis.8 There is compelling evidence that vitamin D acts as a hormetic agent. Low doses of vitamin D exert stimulatory effects upon wound healing, while large doses may inhibit psoriatic plaque. A longitudinal, nested, case-control study of prostate cancer showed that both low (</=19 nmol/l) and high (>/=80 nmol/l) 25(OH)-vitamin D serum concentrations were associated with higher prostate cancer risk, while serum concentrations of 25(OH)-vitamin D within the 40-60 nmol/l range comprised the lowest risk of prostate cancer.9 A biphasic, U-shaped response curve is a characteristic of hormesis.

Clearly, more research is needed to understand how best to evaluate the hormesis hypothesis as applied to calorie restriction, physical exercise, and nutrients like vitamin D in the context of longevity science. In the interim, we are left with the intriguing possibility that stress, when applied carefully and strategically, may be the key to living healthier, longer.


  1. Mitchel REJ. Low doses of radiation are protective in vitro and in vivo: Evolutionary origins. Dose-response. 2006;4(2):75–90.
  2. Mitchel REJ. Low doses of radiation reduce risk in vivo. Dose-Response. 2007;5(1):1–10.
  3. Sakai K, Nomura T, Ina Y. Enhancement of bio-protective functions by low dose/dose-rate radiation. Dose-Response. 2006;4(4):327–332.
  4. Sakai K, Hoshi Y, Nomura T, Oda T, Iwasaki T, Fujita K, Yamada T, Tanooka H. Suppression of carcinogenic process in mice by chronic low dose rate gamma-irradiation. Int J Low Radiat. 2003;1(1):142–146.
  5. Bauer G. Low dose radiation and intercellular induction of apoptosis: potential implications for control of oncogenesis. Int J Radiat Biol. 2007;83(11–12):873–888.
  6. Jürgensmeier JM, Schmitt CP, Viesel E, Höfler P, Bauer G. Transforming growth factor beta treated normal fibroblast eliminate transformed fibroblasts by induction of apoptosis. Cancer Res. 1994;54(2):393–398.
  7. Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science. 1999;285(5432):1390-3.
  8. Norman AW. From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr. 2008;88(2):491S-499S.
  9. Tuohimaa P, Tenkanen L, Ahonen M, Lumme S, Jellum E, Hallmans G, Stattin P, Harvei S, Hakulinen T, Luostarinen T, Dillner J, Lehtinen M, Hakama M. Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries. Int J Cancer. 2004;108(1):104-8.

Men should not stop using Avodart because of heart attack fears! Life Extension’s Rebuttle

Life Extension’s rebuttal by William Faloon in reference to published clinical study in Thursday’s New England Journal of Medicine on Avodart and increased risk for sudden myocardial infarction.

I suspect none of the study participants where using testosterone creams, even though they were ALL likely to be testosterone deficient. You will soon read the findings of an internal study we did on Life Extension Foundation members that found 86% of men have less than optimal testosterone levels.

The significance of this is that testosterone deficiency predisposes a man to heart failure. By taking a drug like Avodart when in a testosterone deficient state, the heart muscle will be robbed completely of this vital anabolic hormone. That may be why this study showed higher heart failure rates in the Avodart group.

 Those with prostate cancer often intentionally suppress their testosterone levels and have to be extra vigilant in protecting against heart attack. Log on to for information on how to protect against multiple risk factors underlying coronary atherosclerosis.

 Aging men (without prostate cancer) should do whatever is necessary to maintain free testosterone blood levels of 20-25 pg/mL, while keeping DHT blood levels at the very low end of the reference range.

This provides the heart, brain and other vital parts their testosterone requirements while protecting the prostate gland against the adverse effects of excess DHT.

 The Avodart study exposes the flaws in so many of these single agent trials. We know, for example, that 25-hydroxyvitamin D serum levels strongly predict prostate cancer risk. If this potent confounding factor was not accounted for, then the results shown with Avodart have little meaning.

If, for example the placebo group’s median 25-hydoxyvitamin D level was 35 ng/mL, and the Avodart group was only 25 ng/mL, this would skew the results in a way to show Avodart less effective than it may really be. Dietary intakes of cruciferous vegetables would have an equally significant confounding effect.

 Bill Faloon