Category Archives: Longevity Medicine

Over at Depressed Metabolism, you'll find a review of The Future of Aging, a book that covers the high points of longevity research and development pretty much from end to end. That includes viewpoints on transhumanist ideals of an ageless society, present work on rejuvenation biotechnology, the cryonics industry, as well as mainstream work on understanding calorie restriction and slowing aging through metabolic manipulation.

Editor-in-chief, cryobiologist, and aging researcher Gregory M. Fahy and his associate editors Michael D. West, L. Stephen Cole and Steven B. Harris have compiled what might be the most impressive collection of articles on interventive gerontology to date in their 866 page collection The Future of Aging: Pathways to Human Life Extension. The book is divided into 2 parts. The first part includes general, scientific, social and philosophical perspectives on life extension. The second part is a collection of proposed interventions, which are organized in chronological order, starting with the (projected) earliest interventions first. Of course, such an organization of the materials necessitates a subjective estimation of when such technologies will be available and is bound to be controversial. The collection closes with a number of appendices about contemporary anti-aging funding and projects (SENS, Manhattan Beach Project).

I wanted to draw your attention to this line of thinking:

One thing that remains a mystery to me is how such an accelerating pace of anti-aging technologies could be validated considering the relatively long life expectancy of humans. Presumably we are expected to adopt a lot of these technologies based on their theoretical merits, success in animal studies, or short-term effects in humans. ... Reading all these inspiring examples, however, I found myself faced with the same kind of despair as when reading about all the neuroprotective interventions in stroke and cardiac arrest. There is great uncertainty how such interventions would fare in humans (or other animals) and, more specific to the objective of human life extension, how we ourselves can ascertain that there are no long-term adverse consequences. ... As reiterated throughout this review, the gold standard and most rigorous determination of the efficacy of anti-aging therapies and interventions is to empirically determine whether they increase maximum human lifespan.

Everyone alive today who ultimately has the chance to benefit from future rejuvenation medicine or methods to significantly slow aging will be using what is at first essentially unproven technology. It will be developed with the best knowledge and insight of the time, but proof is a very high bar when reaching the gold standard involves waiting for decades after the introduction of new therapies. We have a very good grasp of what should extend life and reverse the damage of aging in humans, and it is simply not an option to hold off to see if the first generation of therapies based on this knowledge do in fact extend life in humans. Just as is the case for the practice of calorie restriction today, we will adopt - and are best served by adopting - the use of those technologies that early on in their development can demonstrate (a) extended life in mice, (b) impressive short term changes in the biochemistry of humans, and (c) an acceptable level of observed side-effects and safety.

This all very reasonable given the circumstances: we lack the luxury of time. Facing the choice between calculated risk and the certain suffering that leads to death, sane people will choose risk. Unfortunately, fighting for the right to be able to take that risk - both in medical development and in the use of the resulting biotechnologies - is very necessary, given the present regulatory environment:

Looking back from the perspective of 2035, I guess we should all be surprised that it took so long. The Vegas Group came together formally sometime in 2016, though the first kick-off meeting was the year prior at one of the bi-annual conventions for longevity research held in California. By that time, more than a dozen gene manipulations and other biotechnologies had been shown to significantly extend life in mice, but no progress was being made to develop these technologies for human use. The Vegas Group was a natural outgrowth of a decade of advocacy and anticipation for human enhancement technologies, coupled with the frustrating realization that no such technologies would be meaningfully developed, never mind made available to the public, under the regulatory regimes then in place in the US and Europe.

There were initial fractures in the Vegas Group around the course of political change versus direct action - which led to the formation of another influential movement discussed elsewhere - but by 2017 the direct action contingent of the Vegas Group consisted of about a hundred people all told. Their declared objective was a distributed collaborative effort to (a) develop human versions of the most successful longevity and metabolic enhancements demonstrated in mice, and (b) cultivate hospitable medical groups in the Asia-Pacific countries. When these technologies were developed, the founding members would cast lots and carefully test upon themselves, in rotation, and through the agency of medical centers in Asia. In doing this the hope was to spur change in the public view and greater progress in the commercialization of these technologies - and of course to gain access to manipulations that were greatly extending life in mice.

Over at Depressed Metabolism, you'll find a review of The Future of Aging, a book that covers the high points of longevity research and development pretty much from end to end. That includes viewpoints on transhumanist ideals of an ageless society, present work on rejuvenation biotechnology, the cryonics industry, as well as mainstream work on understanding calorie restriction and slowing aging through metabolic manipulation.

Editor-in-chief, cryobiologist, and aging researcher Gregory M. Fahy and his associate editors Michael D. West, L. Stephen Cole and Steven B. Harris have compiled what might be the most impressive collection of articles on interventive gerontology to date in their 866 page collection The Future of Aging: Pathways to Human Life Extension. The book is divided into 2 parts. The first part includes general, scientific, social and philosophical perspectives on life extension. The second part is a collection of proposed interventions, which are organized in chronological order, starting with the (projected) earliest interventions first. Of course, such an organization of the materials necessitates a subjective estimation of when such technologies will be available and is bound to be controversial. The collection closes with a number of appendices about contemporary anti-aging funding and projects (SENS, Manhattan Beach Project).

I wanted to draw your attention to this line of thinking:

One thing that remains a mystery to me is how such an accelerating pace of anti-aging technologies could be validated considering the relatively long life expectancy of humans. Presumably we are expected to adopt a lot of these technologies based on their theoretical merits, success in animal studies, or short-term effects in humans. ... Reading all these inspiring examples, however, I found myself faced with the same kind of despair as when reading about all the neuroprotective interventions in stroke and cardiac arrest. There is great uncertainty how such interventions would fare in humans (or other animals) and, more specific to the objective of human life extension, how we ourselves can ascertain that there are no long-term adverse consequences. ... As reiterated throughout this review, the gold standard and most rigorous determination of the efficacy of anti-aging therapies and interventions is to empirically determine whether they increase maximum human lifespan.

Everyone alive today who ultimately has the chance to benefit from future rejuvenation medicine or methods to significantly slow aging will be using what is at first essentially unproven technology. It will be developed with the best knowledge and insight of the time, but proof is a very high bar when reaching the gold standard involves waiting for decades after the introduction of new therapies. We have a very good grasp of what should extend life and reverse the damage of aging in humans, and it is simply not an option to hold off to see if the first generation of therapies based on this knowledge do in fact extend life in humans. Just as is the case for the practice of calorie restriction today, we will adopt - and are best served by adopting - the use of those technologies that early on in their development can demonstrate (a) extended life in mice, (b) impressive short term changes in the biochemistry of humans, and (c) an acceptable level of observed side-effects and safety.

This all very reasonable given the circumstances: we lack the luxury of time. Facing the choice between calculated risk and the certain suffering that leads to death, sane people will choose risk. Unfortunately, fighting for the right to be able to take that risk - both in medical development and in the use of the resulting biotechnologies - is very necessary, given the present regulatory environment:

Looking back from the perspective of 2035, I guess we should all be surprised that it took so long. The Vegas Group came together formally sometime in 2016, though the first kick-off meeting was the year prior at one of the bi-annual conventions for longevity research held in California. By that time, more than a dozen gene manipulations and other biotechnologies had been shown to significantly extend life in mice, but no progress was being made to develop these technologies for human use. The Vegas Group was a natural outgrowth of a decade of advocacy and anticipation for human enhancement technologies, coupled with the frustrating realization that no such technologies would be meaningfully developed, never mind made available to the public, under the regulatory regimes then in place in the US and Europe.

There were initial fractures in the Vegas Group around the course of political change versus direct action - which led to the formation of another influential movement discussed elsewhere - but by 2017 the direct action contingent of the Vegas Group consisted of about a hundred people all told. Their declared objective was a distributed collaborative effort to (a) develop human versions of the most successful longevity and metabolic enhancements demonstrated in mice, and (b) cultivate hospitable medical groups in the Asia-Pacific countries. When these technologies were developed, the founding members would cast lots and carefully test upon themselves, in rotation, and through the agency of medical centers in Asia. In doing this the hope was to spur change in the public view and greater progress in the commercialization of these technologies - and of course to gain access to manipulations that were greatly extending life in mice.

Stress appears to affect long-term health and biochemistry in some fundamental ways, some of which are connected to the aging process - such as telomere length, chronic inflammation, and immune system function. So what happens when a person is the opposite of stressed? There is reason to believe that being happy over the long term has just as much of a beneficial effect as stress does a negative effect: "A review of more than 160 studies of human and animal subjects has found 'clear and compelling evidence' that - all else being equal - happy people tend to live longer and experience better health than their unhappy peers. ... Its lead author [analyzed] long-term studies of human subjects, experimental human and animal trials, and studies that evaluate the health status of people stressed by natural events. ... We reviewed eight different types of studies, and the general conclusion from each type of study is that your subjective well-being - that is, feeling positive about your life, not stressed out, not depressed - contributes to both longevity and better health among healthy populations. ... A study that followed nearly 5,000 university students for more than 40 years, for example, found that those who were most pessimistic as students tended to die younger than their peers. An even longer-term study that followed 180 Catholic nuns from early adulthood to old age found that those who wrote positive autobiographies in their early 20s tended to outlive those who wrote more negative accounts of their young lives. There were a few exceptions, but most of the long-term studies the researchers reviewed found that anxiety, depression, a lack of enjoyment of daily activities and pessimism all are associated with higher rates of disease and a shorter lifespan."

Link: http://www.sciencedaily.com/releases/2011/03/110301122156.htm

Some species do not age in any easily detected way - lobsters, for example. Others are just far more resilient to the passage of years than we humans, living longer or losing little of their vitality over the course of their lives. What can be learned from a study of their biochemistry? "The first photo is from 1973, when a dark-haired and spry Nisbet was banding chicks of the small sea bird off the rocky Cape Cod coast. The second photo was taken 33 years later and shows a grizzled, silver-haired Nisbet holding a 29 year old tern, one of the oldest on record. Nisbet's body shows common signs of wear and tear - gray hair, wrinkles, achy joints. The tern, however, shows none of these outward signs, despite being the equivalent of a human centenarian. ... Terns don't even demonstrate diminished physical abilities as they age. They aren't the only animals that have combined a long lifespan with minimal signs of aging; other seabirds, alligators, crocodiles, and some tortoises also seem to sip from the Fountain of Youth. Although medical advances have extended the human lifespan, these same advances haven't been able to prevent the inimical onslaught of old age. Scientists hope that by studying the secrets of ageless critters, humans will one day be able to pause the hands of time. ... The main difference between humans and organisms like common terns is how growing older affects the risk of dying. ... In some animals, like freshwater hydras, risk of death remains pretty constant during life. For other animals, like the tern, the risk of death actually decreases with age. It seems almost counter-intuitive: an older tern is less likely to die than a younger one. 'My 29-year-old tern was still breeding,' Nisbet said. The oldest terns produced the healthiest offspring and were actually more likely to survive the year than younger terns."

Link: http://www.physorg.com/news/2011-03-ageless-animals-scientists-clues-aging.html

Investigating the biochemistry of aging in long-lived species and study of the impact of mitochondrial damage on aging are two quite distinct lines of research. They start to overlap on the matter of lipids, however, and the types and relative proportions of lipids that make up the membranes of cells and cellular components.

If you look back in the Fight Aging! archives, you'll find introductory entries on this topic:

You might recall that different fatty acid or lipid composition in cell membranes was floated as a reason for the ninefold longevity of naked mole-rats over related rodent species. Plenty of oxidative stress in the older mole-rats, but little sign of biochemical damage resulting from it - in comparison to those other rodents long since aged to death, that is. Better, more damage-resistant building blocks down at the molecular level might be the cause.

Better and more damage resistant building blocks: the mitochondrial free radical theory of aging paints mitochondria as the original source of damaging free radicals that react with and destroy cellular machinery - a process that ultimately contributes to age-related conditions such as atherosclerosis. If the machinery is more resistant to free radicals, then we would expect this contribution to aging to have a lesser effect, and thus lead to a longer life span.

If you dig further, you'll see that mitochondrial membrane damage is important in the mitochondrial free radical theory of aging, and the composition of mitochondrial DNA - the blueprint for the proteins that make up mitochondrial structure, such as the membranes - correlate strongly with species maximum life span.

I recently noticed an open access commentary that revisits this area of research:

Scientific investigation of mechanisms that determine lifespan can be divided into three general approaches. The first approach (the comparative method) began over a century ago comparing species differing greatly in maximum longevity and implicated a role for the speed of metabolism in determining the length of life

...

The recent insight from the comparative approach has been to link membrane fatty acid composition to maximum lifespan. This link grew from the finding that membrane fatty acid composition varied systematically with body-size among mammals and the suggestion this caused different cellular metabolic rates in mammals. Membrane fatty acid was then also linked to maximum lifespan (MLSP) variation among mammals. The reason why membrane fatty acid composition is correlated with MLSP is because fatty acids differ greatly in their susceptibility to lipid peroxidation.

Peroxidation of lipids in the body is effectively a form of damage: it is the reaction between a lipid and a free radical, changing the molecular structure of the lipid and rendering it unable to perform its assigned task in the cellular machinery of which it is a part. More resistant lipids means more damage-resistant mitochondria - and damage-resistant mitochondria should translate fairly directly into enhanced life span. So far the evidence supports this way of looking at matters.

That there is such a strong correlation between the building blocks of mitochondrial membranes and species life span is another strong sign that mitochondrial damage is very important in aging - and thus we should prioritize present efforts to support the development of biotechnologies that can repair or replace mitochondria throughout the body. These therapies are tantalizingly close to realization, but progress is slow and will remain slow until such time as funding and public interest are much larger than they are today.

A study conducted by CSIRO researchers found that a minimal intake of 3.8 grams of salt, which is equivalent to the salt content of most meals, can affect blood circulation.

Salt is an essential food ingredient needed to keep the body functioning properly. Sodium, a major extracellular ion, is needed by the cells to regulate mechanisms such as muscular contraction and water-base balance. In other words, the nutrients in salt helps maintain the right balance of water and other fluids in the body, influence the relaxation and contraction of muscles, and transmit nerve impulses.

The kidneys are responsible for maintaining the balance of sodium in the body in order to maintain optimal health by excreting it as urine. But these tiny organs that’s just as small as a common computer mouse has its limitations; it can only take a maximum of 2 to 3 tablespoons of salt in a day. Salt that fails to be excreted will start to accumulate in the blood and this could ultimately result to higher blood volume. In effect, the heart will have to work harder in order to properly circulate blood through the blood vessels. This results to higher blood pressure. Diseases linked to this condition are chronic kidney disease, cirrhosis, hypertension, congestive heart failure and a few others.

Immediate Effects of Sodium to Blood Circulation

A study published in the American Journal of Nutrition showed that salty foods can start to adversely affect blood circulation 30 minutes after consumption. The researchers found that eating foods containing 3.8 grams of salt of can inhibit the ability of blood vessels to expand and added that blood flow mediated dilation is reduced within 30 minutes after the meal.

The researchers from CSIRO, or the Commonwealth Scientific and Industrial Research Organization, in Australia reported that eating meals rich in sodium can reduce the ability of the blood vessels to dilate by 50 percent compared to low-sodium meals. But they added that normal blood vessel function was restored after 2 hours. The lead author of the study, Kacie Dickinson, said that they were surprised to see a similar response to eating foods rich in saturated fats which has been known to damage the blood vessels on a long-term basis.

In the study, the researchers gathered a group of sixteen healthy volunteers and observed the postprandial effects of high salt intake to the endothelial function of study participants which, if impaired, is linked to a higher risk of developing cardiovascular disease and hypertensive disorder. The researchers found that eating either high or low sodium meals can affect the natural ability of blood vessels to expand.  But meals higher in sodium can result to a more significant change.

Food Sources

Knowing the foods that are high in sodium content is the best way of keeping an eye on your sodium intake. Some of the foods richest in sodium are kelp, garbanzo beans, some fruits, dry lotus stems, corn meal, chick peas, cheese, celery, canned foods, buttermilk, black-eyed beans, beets and meats. Fast foods like fries and burgers are high in salt.  People with hypertensive conditions needs to be more wary about their sodium intake due to the risks involved. Healthy people, on the other hand, need to take as much care to prevent the development of the disease. Though sodium from salt offers the body numerous health benefits, the adverse effects of too much sodium are enough reason to read food labels and be well-educated about how to maintain a healthy balance of sodium in the body.

Detecting High Sodium: how to Read Food Labels

Not all foods rich in sodium taste salty. A typical bagel, for example, has 532 milligrams of sodium. So it is always important to read food labels and scan through the Nutritional Facts to know if the food contains more sodium than what your body needs. If you are reading the ingredients, some of the substances that contain sodium are monosodium glutamate, sodium nitrate and sodium nitrite, sodium alginate, disodium phosphate, baking powder and baking soda. These ingredients are present in most processed goods.

Some foods also have sodium labels on them. “Unsalted” or “no salt added” means no salt was added in the processing of these foods. But these foods may still have sodium in them. “Light” or “light in sodium” means sodium content has been reduced by 50 percent to the regular variety, “low sodium” products contains 140 milligrams of sodium at most, “very low sodium” indicates 35 milligrams of sodium per serving, and “sodium free” means the food has less than 5 milligrams of sodium.

Healthy and Natural Alternative to Salt

It is possible to supply the body with sodium without taking too much salt. Sodium is a natural occurring nutrient in plants. So using certain plant ingredients like celery and beans in cooking can give dishes a salty taste and at the same time give you just the right amount of sodium. Organic sea salt, on the other hand, can be a better and healthier alternative.

Table salt and organic sea salt has the same nutritional value both consisting of two major mineral components namely sodium and chloride. They contain similar amounts of sodium but the difference primarily lies in the way there were processed. Table salt is usually mined underground and it needs more processing to remove harmful trace minerals and is commonly fortified with iodine. Chemicals are also added to table salt to avoid clumping. Organic sea salt is harvested from evaporated sea water. It undergoes minimal processing and only contains minimal amounts of trace minerals. Sea salt also naturally contains iodine. But regardless of where you are getting your sodium from, it is always important to keep it at a minimum.

Natural Ways to Lower Risk of Hypertension and CVD

The risk factors of hypertension and cardiovascular disease are high alcohol intake, excess weight, lack of exercise, high sodium intake, and high blood cholesterol level. So in order to avoid hypertension, it is only appropriate to keep an active lifestyle, maintain a diet that’s low in sodium and bad cholesterol, keep a healthy body mass index and keep liquor to a moderate. These habits do not only keep the circulatory system health, but they have other health benefits like reduced risk of diabetes, obesity and chronic diseases.

Sources
foodnavigator.com
mayoclinic.com
lifestyle.iloveindia.com
associatedcontent.com
mayoclinic.com

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