Hormesis, cell death and aging

Hormesis, cell death and aging

Isabelle Martins, Lorenzo Galluzzi and Guido Kroemer

Abstract

Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress response that raise the resistance of the organism against high doses of the same agent. This phenomenon, which is known as "hormesis", is best represented by ischemic preconditioning, the situation in which short ischemic episodes protect the brain and the heart against prolonged shortage of oxygen and nutrients. Many molecules that cause cell death also elicit autophagy, a cytoprotective mechanism relying on the digestion of potentially harmful intracellular structures, notably mitochondria. When high doses of these agents are employed, cells undergo mitochondrial outer membrane permeabilization and die. In contrast, low doses of such cytotoxic agents can activate hormesis in several paradigms, and this may explain the lifespan-prolonging potential of autophagy inducers including resveratrol and caloric restriction.

Paleo Diet

From http://www.paleonu.com/panu-weblog/2009/11/13/what-i-eat.html

Paleo diet:-

>> I don't count, weigh or measure and I only look up the contents of what I am eating for research purposes (curiosity or the blog).

I eat about 5 % of calories as carbohydrate right now. Partly that is because I seem to be somewhat starch intolerant and I see little point in adding things like potatoes and rice that I didn't eat much before. It is not because I am specifically following Kwasneiwski's optimal diet, it just works out that way. But many of my own premises lead the same direction as Kwasniewski, so that's just confirmation in my mind. I suspect anything from 0-30% carbs will work fine (for health) for most people. If you want to go beyond that to Kitavan levels with Yams or white rice, I doubt if that is as healthy, but that might be OK, too if you have extirpated the neolithic agents.

My staples are:

Grass fed beef and lamb, wild venison (whitetail deer), bison. I eat the hearts and livers, don't care for the kidneys. Codfish, wild salmon and trout from lake michigan, sashimi (maguro especially). Wild turkey (the bird not the liquor)

Eggs - pastured eggs averaging 4 a day - often garnished with green or red chili salsa and sour cream. Onions and mushrooms for accompaniment.

Whole cream - in coffee and straight up. Diesel #1.

Pastured butter - I use it to cook everything and add it to stews and chili. Diesel #2.

Bacon, smoked bacon and prosciutto ham maybe once a week. (Penn Jillette says bacon is the perfect food)

Occasional sardines in olive oil or water.

Cheeses - Gorgonzola, parmesan, cheddar, brie, etc.

Veggies mostly as condiments - Red, yellow and white onions, regular and portabella mushrooms, wild morels and chantarelles in season, asparagus, green beans, different varieties of chilis.

Our main fruit is tomatoes eaten whole or crushed in tomato sauce for stew or chili. Lots of avocado with breakfast. A handful of raspberries and occasionally blueberries topped with unsweetened whole whipped cream now and then. Add vanilla to the whipped cream.

"Nuts" - limited pecans, almonds and walnuts - not for health just for flavor.

Any day we eat factory meat or get a big dose of n-6 PUFAs in restaurant food (Mcdonald's burger without bun, barbecued store bought chicken, restaurant eggs fried in vegetable oil) we each take 1 teaspoon of Carlson's cod liver oil.

You know about the vitamin D - now 8000 units/day Carlson's drops in morning coffee.

Hormesis: COLD

From Own Your Health - http://is.gd/ieMRi

Cold Showers: What’s the Evidence?

Some people have questioned the evidence behind hydrotherapy, especially the cold water treatments that are described in the book that Alexa Fleckenstein and I co-authored. German research supports the effects of cold water used on the skin as therapy. Unfortunately, the studies are in German, and they are small. (1) Because Pharma firms have no interest in inexpensive water cures, there probably won’t be big studies any time soon. Fact is, the German insurance system pays all or part of physician-prescribed treatments, including hydrotherapy and herbs. The importance and therapeutic potential of water, and especially cold water, are now simply taken for granted in Germany.(2) Here are some specific research studies supporting the health benefits of cold water treatments. Citations are listed at the end. (More cold water research details in Own Your Health (2003)

Boosting the immune system
A pilot study of immune effects from cold water therapy with a small number of breast cancer patients found significantly increased disease-fighting cell counts in every category examined, including neutrophils, lymphocytes, monocytes.(3)

Reducing the perception of pain
In a study in Japan, cooling by ice water was one of the “competitive stimuli” that reduced the perception of the pain of a laser beam on the skin. (4)

Improved circulation and function in the legs
A Swedish group administered three weeks of alternating cold and hot hydrotherapy to the legs of patients suffering from intermittent claudication (reduced blood flow) and found that improved systolic blood pressure in ankles and toes, reduced pain, and markedly better walking ability went beyond the results of standard treatment and persisted for at least a year after treatment.(5)

Swimming in the winter?
Ten healthy subjects who regularly swim during the winter were evaluated at Berlin’s Institute of Biochemistry at Humboldt University Medical School. Their blood and urine showed increased levels of anti-oxidants, which prevent cell damage, indicating their bodies’ increased tolerance to stress.(6)

(1)Summarized in Bühring, M., Naturheilkunde: Grundlagen, Anwendungen, Ziele (Natural Medicine: Basic Application and Goals), Munich, Verlag CH Beck, 1997.
(2)Haas, S.S., Hydrotherapy and more: Adapting Kneipp’s Natural Medicine to the U.S., Complementary Medicine for the Physician, 2000; 5(8):57,61-64.
(3)Kuehn, G., Sequential hydrotherapy improves the immune response of cancer patients. In: Mizrahi A, et al., (eds.) Potentiating Health and the Crisis of the Immune System: Integrative Approaches in the Prevention and Treatment of Modern Diseases. New York: Plenum, 1997.
(4)Kakigi R., et al. Pain relief by various kinds of interference stimulation applied to the peripheral skin in humans: pain-related brain potentials following CO2 laser stimulation. J peripher Nerv Syst 1996;1:189-198.
(5)Elmstahl, S. et al., Hydrotherapy of patients with intermittent cluadication: a novel approach to improve systolic ankle pressure and reduce symptoms. Int Angiol. 1995;14:389-394.
(6) Siems, W.G., et al., Uric acid and glutatione levels during short-term whole body cold exposure. Free Radic Biol Med. 1994;16:299-305.

Take a Cold Shower to Protect Against Colds and Flu This Winter

At first, it sounds crazy – can a cold shower really prevent colds and flu? But Dr. Alexa Fleckenstein, author of HEALTH 2 0: TAP INTO THE HEALING POWERS OF WATER TO FIGHT DISEASE, LOOK YOUNGER, AND FEEL YOUR BEST (McGraw-Hill 2007) says that a few seconds of cold water after your hot shower is scientifically proven to make you healthy – even if you’re in the cold water for less than 30 seconds a day.

Here are 6 ways that a short cold shower protects you from colds and flu:

1. A brief cold water shower will decrease your body’s “reaction time” to cold. The cold shower “teaches” the blood vessels in your skin to clamp down faster, so you are losing less warmth in draft or cold exposure. Especially, during the winter months while it’s cold outside, you’ll stay warmer, longer.

2. Gamma interferon and interleukin-4 are two important virus-fighting cytokines (immune system proteins) A new German study has shown that cold water exposure helps these two disease-fighters work better together, resulting in fewer viral colds.

3. A cold shower increases lymphocytes in the blood. Lymphocytes produce antibodies, which help fight germs.

4. A cold shower makes you breathe deeply. (A big gasp when the cold water hits the skin!) A deep breath opens closed or clogged alveoli (small air sacs in the lungs) which are then less prone to bronchitis and pneumonia. And deeper breathing means more oxygen for the whole body.

5. A cold shower increases blood flow in all organs, especially skin, heart and lungs. The pharynx/larynx ( organs of the throat) also benefit from the increased blood flow, and are better able to kill viruses.

6. And a cold shower lifts your mood. Depressed people get more colds – probably because depression lowers immunity. A brisk cold shower has been proven to lift the mood and lower stress, both of which jumpstart the immune response – which kills flu and cold germs!

Remember that cold water therapy works only if done regularly, and also needs a few weeks (about six) to work. Start with just your feet and hands in the cold water, and gradually work your way up to your whole body. It feels great!

IMPORTANT: Check with your doctor first. Contraindication include uncontrolled high blood pressure, and narrowing of the arteries.

anti-agingfirewalls.com

The process of hormesis is thought to be mediated primarily via heat shock proteins (HSPs). This blog further explores how hormesis and heat shock proteins work, focusing primarily on the HSP70 superfamily of proteins... the complexity of the biomolecular processes involved... http://anti-agingfirewalls.com/2010/07/03/hsp70-to-the-rescue/

Getting Stronger

Great source of information on all things hormesis:
http://gettingstronger.org/hormesis/

Does caloric restriction increase longevity?

Does caloric restriction increase longevity? Perhaps not - at least not in the way postulated in much of the media - unless you are a black 6 mouse...

Greg Critser (new book is Eternity Soup: Inside The Quest To End Aging,Harmony 2010):-

"Hormesis theory — the notion that caloric restriction (the only intervention that expands maximum lifespan in mammals — mice) works by putting the body in a kind of energy-saving hibernation state, is promising. But the pathway by which it seems to work—ratcheted down Insulin-like Growth Factor 1 (IGF-1), does not seem implicated in exceptional human longevity; in one recent study only 6 of 220 human centenarians had the mutated IGF -1 receptor. Also, human beings do very badly on low IGF 1. They get sick and die". See
http://www.scientificblogging.com

Hormesis and hormetins

From: http://hubpages.com/forum/topic/28456
Three main categories of hormetins can be:

-Physical hormetins - exercise (running, walking, weight lifting etc), temperature (hot sauna or cold baths), irradiation (sunlight, solar-treatments)

- Nutritional hormetins - food restriction (fasting, low calorie diet), spices (turmeric, clove), zinger, garlic, onion, and micronutrients (zinc). There are many many more nutritional hormetins yet to be identified, and synthetic hormetins yet to be synthesized.

- Mental hormetins - mental activity (reading, puzzle solving, chess), public speaking/performance, focussed attention (meditation), "falling" in love....

Accordingly, several dietary components, such as resveratrol, vitamins, and trace elements and minerals including iron, iodine, fluorine, selenium and copper and zinc are potential hormetins. Other potential hormetins are the so-called antioxidants such as alpha lipoic acid and coenzyme Q10 which, owing to their pro-oxidant activities in producing hydrogen peroxide, induce antioxidative defensive responses and ultimately may bring about beneficial effects. Another hormetin is a plant growth factor kinetin, which we have snown to have several anti-ageing effects in human skin cells, promotes the differentiation of keratinocytes by inducing stress response pathways.

Similarly, some components of certain medicinal plants used frequently in the traditional Chinese medicine and in the Indian Ayurvedic system of medicine are claimed to have anti-aging effects, which appear to be achieved through hormetic pathways. For example, celasterols and paeoniflorin present in some medicinal herbs have cytoprotective effects and induce HSP in human cells. Leaf extracts of Ashwagandha (Withania somnifera) also induce HSP synthesis in mammalian cells, which may be one of the reasons for its observed beneficial medicinal effects.

Curcumin: Another potential hormetin being tested for its biological effects is curcumin or diferuloylmethane. It is the active component in the commonly used food spice turmeric, and is derived from the roots of Curcuma longa. Curcumin is a co-inducer of HSP and has wide ranging biological effects depending on its dosage. We have undertaken studies to check the hormetic effects of curcumin on human keratinocytes and fibroblasts. We have previously reported that at lower doses (0.3 and 1 μM) curcumin stimulates proteasome activity, enhances HSP induction after HS, and stimulates sodium pump activity. We are now extending these studies to find out long term effects of curcumin treatment on cellular aging, differentiation and angiogenesis.

Rosmarinic acid: Another potential hormetin that we are testing is the rosmarinic acid (RA), which is a phenolic compound present in several medicinal plants such as those from the Labiatae family, for example Salvia officinalis (common sage) and Rosmarinus officinalis. We are now in the process of testing further the short term and the long terms effects of the hormetin RA on aging, wound healing, angiogenesis and differentiation of human cells. Our preliminary results show that human skin fibroblast cultures grown continuously in the presence of 20 μM RA for 50 days have a significant (33%) reduction in the number of cells showing senescence-specific β-galactosidase marker. Furthermore, there was 50% reduction in the proportion of enlarged cell population with high levels of green autofluorescence in RA-treated cultures, as measured by flow cytometery.


In conclusion, using human fibroblasts, keratinocytes, endothelial cells and bone marrow mesenchymal stem cells we have provided evidence in support of the view that hormesis can be applied successfully to aging research and intervention. This includes the effects of mild HS on various parameters of cellular aging and other functional characteristics, such as differentiation, wound healing and angiogenesis.