{"id":411,"date":"2015-08-07T13:35:22","date_gmt":"2015-08-07T13:35:22","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=411"},"modified":"2016-01-05T13:04:07","modified_gmt":"2016-01-05T13:04:07","slug":"the-mystery-of-aging-solved-at-last","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/08\/07\/the-mystery-of-aging-solved-at-last\/","title":{"rendered":"The Mystery of Aging, Solved at Last!"},"content":{"rendered":"

How many headlines have you seen that purport\u00a0to reveal THE secret of aging? \u00a0Just in the last few weeks, \u00a0there have been several fundamental, earthshaking, paradigm-shifting, game-changing, disruptive discoveries–and they were very different one from another.<\/p>\n

Why do these headlines keep popping up? \u00a0Is there truth in any of them? \u00a0…and, most interesting to me, What is it that they are all<\/b> missing?<\/em><\/p>\n

I\u2019m a culprit in this game, too. \u00a0My publisher wants to call my forthcoming book Cracking the Aging Code<\/a>.<\/p>\n

I\u2019m going to cover seven of these news releases below; I trust you\u2019ll let me know if you want to hear more about any of them in particular.<\/p>\n\n\n\n
What to Eat while Fasting<\/b>I have posted a page of recipes<\/a> for my variation on Longo\u2019s Fasting-Mimicking Diet<\/a>. \u00a0These recipes are not endorsed by Dr Longo, but they have the same profile of macronutrients (calories, protein, fats, carbohydrates) as the products soon to be available from L-Nutra<\/a>.<\/p>\n

These recipes are based on fresh foods, and the fiber content is much higher than the FMD that Dr Longo has tested<\/a>. \u00a0Intuition tells me that fiber can only add benefit, but this is untested.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Delay of Aging by Remote Control<\/b><\/p>\n

\u201cUCLA biologists have identified a gene that can slow the aging process throughout the entire body when activated remotely in key organ systems.\u201d \u00a0[Science Daily<\/a> from last fall]<\/p>\n

AMP Kinase is a key chemical workhouse for energy production and regulation. \u00a0In this study, the AMPK gene in fruit flies was found to be a signal that controls autophagy throughout the body. \u00a0(Background: Autophagy<\/a> is recycling at the cellular level. \u00a0It declines through the life span, with the result that molecular gunk accumulates and production of properly-formed proteins declines.)<\/p>\n

Life span and health span of the flies were increased when the gene for AMPK was activated in the nervous system, and independently in the digestive system.<\/p>\n

 <\/p>\n

Role of Mitochondrial Damage vs Epigenetics<\/b><\/p>\n

Jun-ichi Hayashi of Tsukuba University was an early enthusiast of the mitochondrial free radical theory of aging, who became convinced by his own lab results that the theory doesn\u2019t work.<\/p>\n

Background: Mitochondria are thousands of organelles inside\u00a0a cell that burn sugar for electrochemical energy that the cell can use. \u00a0They have their own DNA and their own reproductive cycles within a cell. \u00a0They generate reactive oxygen species (ROS) as a byproduct, and it was an attractive theory to attribute aging to damage and mutations they suffer because they are at ground zero for high concentrations of ROS.<\/p>\n

Over the last two decades, we have learned that mitochondria do indeed play a central role in aging, but the story is not about simple damage. \u00a0In his latest paper [research article<\/a>, Science Daily report<\/a>], researchers from Hayashi\u2019s lab show that there is no difference in the amount of DNA damage in mitochondria from cells of young people and from old people. \u00a0Why then do mitochondria perform less well, and provide less energy in older people? \u00a0They go on to propose that it is the epigenetic programming (in the cell nucleus, not the mitochondria) that makes the difference, and they identified two genes (GCAT and SHMT2) \u00a0that may be all that is needed to restore youthful function to the mitochondria. \u00a0These genes control production of glycine, the simplest of the 20 amino acids that are common protein constitutents. \u00a0Simply feeding the cells with glycine also improved mitochondrial function. \u00a0(You can buy glycine tablets as a supplement, but the body already has a lot, so it\u2019s a good guess you would need a lot of it to make a difference. \u00a0Food sources rich in glycine<\/a> include gelatin, shrimp, spirulina, and raw ostrich meat.)<\/p>\n

 <\/p>\n

Simple Flip of a Genetic Switch<\/b><\/p>\n

Johnathan Labbadia at Northwestern University has discovered an epigenetic switch, a set of genes that is turned on that begins the aging process in lab worms [Research article<\/a> from the Morimoto lab, Science Daily summary<\/a>]. \u00a0Worms begin aging at the tender age of 3 days, just a few hours after adulthood, with a switch that represses Heat Shock Protein. \u00a0HSP is not jus for heat, but a high-level signal that invokes a set of responses that create resiliency in response to stress of many kinds. \u00a0In worms and in other animals, stress resistance is closely associated with longevity, and HSP is associated with longer life span in worms [ref<\/a>].<\/p>\n

Scientists who see aging as a purposeful, programmed event, myself included, look to mechanisms of epigenetic control, as we are hopeful that signaling can be modified to avert aging. \u00a0But traditional evolutionary biology denies that there can be such direct control of aging. \u00a0According to theory, such switches could only be flipped if flipping them increased reproduction in a way that more than offsets the loss of reproductive opportunity from aging. \u00a0In keeping with the standard theories, Labbadia and Morimoto, looked for a connection to reproduction in the epigenetic switch they discovered. \u00a0They found one, but–undermining the theory–they found that the benefits for reproduction and the costs in the form of aging could be easily separated.<\/p>\n

\u201cIn one experiment, the researchers blocked the germline from sending the signal to turn off cellular quality control. They found the somatic tissues remained robust and stress resistant in the adult animals.\u201d<\/p><\/blockquote>\n

Why doesn\u2019t the worm do this, and get the best of both? \u00a0Must be some kind of mistake, the Northwestern team asserts. \u00a0\u201cDysregulation\u201d has become a favorite word, though many have enough integrity and insight to be scratching their heads, wondering why there should be so much \u201cdysregulation\u201d involved in aging, when we rarely find anything else about the metabolism that is consistently dysregulated.<\/p>\n

 <\/p>\n

Older Blood Vessels are Better Protected against Oxidative Stress<\/b><\/p>\n

This press release<\/a> from University of Missouri descirbes evidence that cells of the arterial lining (epithelium<\/a>) are more resistant to oxidative damage when they are older. \u00a0Research from the lab of Steven Segal used hydrogen peroxide (H2O2) as a stressor. \u00a0Peroxide is also known to be a multi-purpose signal molecule that can induce cell suicide (apotosis) in high concentrations, and can induce protective anti-aging response at lower levels [ref<\/a>, ref<\/a>].<\/p>\n

The article is framed within an old and discredited view of that regards aging as a simple result of oxidative damage [ref<\/a>].<\/p>\n

\u201c<\/i>Although the causes of many age-related diseases remain unknown, oxidative stress is thought to be the main culprit. Oxidative stress has been linked to cardiovascular and neurodegenerative diseases including diabetes, hypertension and age-related cancers.\u201d <\/i><\/p><\/blockquote>\n

It should no longer surprise us that anti-oxidants are not anti-aging [ref<\/a>], or that pro-oxidants can be anti-aging [ref<\/a>], or that aging is an active process controlled by central signals, not a passive process of damage [ref<\/a>].<\/p>\n

 <\/p>\n

Getting to the Bottom of Aging<\/b><\/p>\n

This article claims to find the root of aging at the cellular level. \u00a0In particular, it is in the endoplastic reticulum<\/i><\/a> [background in a Kahn video<\/a>]. The ER is a transport network inside the cell that directs each protein molecule to a targeted location. \u00a0It does more than this–it finishes and folds the protein after it is manufactured. \u00a0The new study<\/a> finds differences between the ER of old and young cells, studied in lab worms and in cultured human cells. \u00a0[Here is a Science Daily summary<\/a>.] \u00a0Proteins tend to be misformed and misfolded by the ER of old cells..<\/p>\n

In direct contrast to the article just above on blood vessels (\u201coxidative stress is thought to be the main culprit\u201d ), the claim here is that there is not enough<\/i> oxidation in the ER of old cells. \u00a0It is the reduced state of the ER that is responsible for misfolding of proteins.<\/p>\n

 <\/p>\n

Diverging Paths from Parabiosis Experiments: \u00a0GDF11 and TGF-\u03b2 <\/b><\/p>\n

In the early 2000s, Irina Conboy and Amy Wagers were grad students in Tom Rando\u2019s Stanford University lab, studying parabiosis in mice. \u00a0They learned that tissues in an old mouse could be rejuvenated by exchanging blood plasma with a young mouse.<\/p>\n

Blood plasma is the liquid, containing dissolved signal molecules but no whole blood cells, no stem cells. \u00a0The implication was that the old tissues could receive instructions from other parts of the body (an epigenetic clock<\/a>?) causing them to get older or to revert to a younger state.<\/p>\n

Following up on this work: Now Irina and her husband Mike Conboy have a lab at UC Berkeley, where they are focusing on TGF-\u03b2 as one of the signals that causes aging. \u00a0They are experimenting with a drug that blocks TGF-\u03b2 receptor, and found that it has rejuvenating effects both on muscle and brain cells [press release<\/a>, research article<\/a>]. \u00a0The implication is that excessive TGF-\u03b2 in the blood is a source of aging.<\/p>\n

Wagers is at the Harvard Stem Cell Center, where her biggest trophy so far is the discovery that GDF11 has rejuvenating effects in muscle and nerve cells<\/a>. \u00a0The implication is that there is not enough GDF11 in the blood in the blood of older mammals, and this is a source of aging.<\/p>\n

The irony is that GDF11 is a form of TGF-\u03b2. \u00a0The findings of Wagers and Conboy have diverged to the point where they have focused on the same signal as pro-aging (Conboy) and anti-aging (Wagers).<\/p>\n

I don\u2019t have the expertise to take sides in this disagreement, but others have noted that Wagers\u2019s claim seems counter-intuitive. Doubts were expressed about Wagers\u2019s findings by researchers at Novartis (a Cambridge, MA pharmaceutical lab), where David Glass claims<\/a> he has been unable to duplicate Wagers\u2019s work, and that in his experiments with mice, GDF11 seems to decline with age.<\/p>\n

Wikipedia<\/a> says, \u201cGDF11 is a myostatin-homologous protein that acts as an inhibitor<\/i><\/b> of nerve tissue growth. GDF11 has been shown to suppress neurogenesis through a pathway similar to that of myostatin<\/a>.\u201d [emphasis added]. \u00a0Myostatin is an inhibitor of muscle growth whose structure is 90% homologous to GDF11.<\/p>\n

\"\"
Images of cells in the brain\u2019s hippocampus show that the growth factor TGF-beta1 (stained red) is barely present in young tissue but ubiquitous in old tissue, where it suppresses stem cell regeneration and contributes to aging.<\/figcaption><\/figure>\n

\u201cThe challenge ahead is to carefully retune the various signaling pathways in the stem cell environment, using a small number of chemicals, so that we end up recalibrating the environment to be youth-like,\u201d Conboy said. \u201cDosage is going to be the key to rejuvenating the stem cell environment.\u201d<\/p>\n

 <\/p>\n\n\n\n
Keeping your Brain Active with Balance Exercises<\/b><\/p>\n

A pilot study<\/a> by Ross and Tracy Alloway of Univ North Florida suggests that balance exercises improve working memory and protect against neurodegenerative disease. [UNF press release<\/a>] \u00a0The focus of the study is termed \u201cproprioception\u201d, awareness of body position.<\/p>\n

We all lose brain cells with age, and I think of Alzheimer\u2019s dementia as one end of a spectrum. \u00a0Some herbs<\/a> have been studied for neuroprotective effects. \u00a0Vigorous exercise<\/a> is neuroprotective.<\/p>\n

In parallel to my life as a scientist, I have always practiced yoga and I have taught one yoga class each week for almost 40 years. \u00a0Balance exercises are an essential aspect of yoga. \u00a0Intuition tells me there is an anti-aging benefit in yoga practice, and there is implicit evidence<\/a> for this. \u00a0I think the connection between yoga and aging deserves a lot more study, but of course it cannot be done with animals, and blinded, controlled experiments are not feasible.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n","protected":false},"excerpt":{"rendered":"

How many headlines have you seen that purport\u00a0to reveal THE secret of aging? \u00a0Just in the last few weeks, \u00a0there have been several fundamental, earthshaking, paradigm-shifting, game-changing, disruptive discoveries–and they were very different one from another. Why do these headlines keep popping up? \u00a0Is there truth in any of them? \u00a0…and, most interesting to me, … Read more<\/a><\/p>\n","protected":false},"author":65,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-411","post","type-post","status-publish","format-standard","hentry","category-uncategorized"],"yoast_head":"\nThe Mystery of Aging, Solved at Last! - Josh Mitteldorf<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/08\/07\/the-mystery-of-aging-solved-at-last\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The Mystery of Aging, Solved at Last!\" \/>\n<meta property=\"og:description\" content=\"How many headlines have you seen that purport\u00a0to reveal THE secret of aging? \u00a0Just in the last few weeks, \u00a0there have been several fundamental, earthshaking, paradigm-shifting, game-changing, disruptive discoveries–and they were very different one from another. 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\\\/\\\/mathforum.org\\\/~josh\",\"sameAs\":[\"http:\\\/\\\/AgingAdvice.org\"],\"url\":\"https:\\\/\\\/scienceblog.com\\\/joshmitteldorf\\\/author\\\/joshmitteldorf\\\/\"}]}<\/script>\n<!-- \/ Yoast SEO Premium plugin. -->","yoast_head_json":{"title":"The Mystery of Aging, Solved at Last! - Josh Mitteldorf","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/08\/07\/the-mystery-of-aging-solved-at-last\/","og_locale":"en_US","og_type":"article","og_title":"The Mystery of Aging, Solved at Last!","og_description":"How many headlines have you seen that purport\u00a0to reveal THE secret of aging? \u00a0Just in the last few weeks, \u00a0there have been several fundamental, earthshaking, paradigm-shifting, game-changing, disruptive discoveries–and they were very different one from another. Why do these headlines keep popping up? \u00a0Is there truth in any of them? \u00a0…and, most interesting to me, ... 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The surprising fact that our bodies are genetically programmed to age and to die offers an enormous opportunity for medical intervention. It may be that therapies to slow the progress of aging need not repair or regenerate anything, but only need to interfere with an existing program of self-destruction. Mitteldorf has taught a weekly yoga class for thirty years. He is an advocate for vigorous self care, including exercise, meditation and caloric restriction. After earning a PhD in astrophysicist, Mitteldorf moved to evolutionary biology as a primary field in 1996. He has taught at Harvard, Berkeley, Bryn Mawr, LaSalle and Temple University. He is presently affiliated with MIT as a visiting scholar. In private life, Mitteldorf is an advocate for election integrity as well as public health. He is an avid amateur musician, playing piano in chamber groups, French horn in community orchestras. His two daughters are among the first children adopted from China in the mid-1980s. Much to the surprise of evolutionary biologists, genetic experiments indicate that aging has been selected as an adaptation for its own sake. This poses a conundrum: the impact of aging on individual fitness is wholly negative, so aging must be regarded as a kind of evolutionary altruism. Unlike other forms of evolutionary altruism, aging offers benefits to the community that are weak, and not well focussed on near kin of the altruist. This makes the mechanism challenging to understand and to model. more at http:\/\/mathforum.org\/~josh","sameAs":["http:\/\/AgingAdvice.org"],"url":"https:\/\/scienceblog.com\/joshmitteldorf\/author\/joshmitteldorf\/"}]}},"jetpack_featured_media_url":"","jetpack_shortlink":"https:\/\/wp.me\/pgtN8h-6D","jetpack_sharing_enabled":true,"_links":{"self":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/411","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/users\/65"}],"replies":[{"embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/comments?post=411"}],"version-history":[{"count":0,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/posts\/411\/revisions"}],"wp:attachment":[{"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/media?parent=411"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/categories?post=411"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/scienceblog.com\/joshmitteldorf\/wp-json\/wp\/v2\/tags?post=411"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}