{"id":333,"date":"2015-01-27T18:07:33","date_gmt":"2015-01-27T18:07:33","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=333"},"modified":"2015-01-27T18:07:33","modified_gmt":"2015-01-27T18:07:33","slug":"myc-bad-and-good-but-more-bad-than-good","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2015\/01\/27\/myc-bad-and-good-but-more-bad-than-good\/","title":{"rendered":"MYC: Bad and Good, but More Bad than Good"},"content":{"rendered":"

MYC is the name of a gene that promotes cancer. \u00a0We\u2019ve known this since the 1970s. \u00a0Trouble is, MYC is also necessary for growth, so we can\u2019t eliminate it, and we\u2019ve been very careful about targeting targeting MYC for inhibition, except in the extreme case of cancer patients. \u00a0That\u2019s why we didn\u2019t learn until last week that mice with half as much MYC live longer and seem healthier in every way.<\/i><\/p>\n

The standard theory of why we age is called \u201cAntagonistic Pleiotropy\u201d, a fancy way of saying that nature has been forced to compromise. \u00a0Natural selection rewards long life, it is true, but also rewards rapid growth and high fertility. \u00a0It is genes like MYC that force nature into a kind of devil\u2019s bargain, accepting a cancer risk (and a shorter life) as a necessary concomitant of growth and fertility.<\/p>\n

This idea was a gift of George Williams [1957<\/a>], last week\u2019s featured celeb here at Aging Matters<\/i>, and for more than 50 years it has been so well-established that scientists presume–not just evolutionary scientists, but also clinicians and medical researchers presume that nature has done her best by us, and we oughtn\u2019t to tamper with the mix of genes that Nature has bequeathed us.<\/p>\n

Inserting or deleting a gene has become so routine in thousands of research labs around the world that it is only surprising it has taken so long before researchers at Brown University prepared mice with one parental copy of the MYC gene missing, and the second intact. \u00a0Last week they reported that the mice lived longer, were less susceptible to cancer, were more active, had healthier blood lipid profiles, and their immune function remained stronger, longer. \u00a0Heart muscles stayed more pliable, and cholesterol buildups occurred later. \u00a0The mice died of the same cancers as normal lab mice, but later. \u00a0(Mice missing both copies of MYC are not viable.)<\/p>\n

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Most interventions that extend life span in mice work by dialing up the stress response system. \u00a0This is the mechanism of hormesis<\/i>, a beneficial over-compensation to stress. \u00a0Caloric restriction is the most common and most consistent way to activate this pathway. \u00a0So it is interesting to note that the mice with reduced MYC did not have increased stress response, nor did they eat less than normal mice. \u00a0This suggests that the life extension benefit of reduced MYC might be able to synergize with caloric restriction to offer additive benefit.<\/p>\n

Many anti-aging measures have tradeoffs. Mice given rapamycin, for instance, have increased cardiovascular disease risk and reduced immune function. In contrast, mice with reduced MYC showed no obvious health problems and were able to reproduce normally. [ref<\/a>]<\/em><\/p><\/blockquote>\n

Life span was extended 20% for females, 10% for males. \u00a0This, too, is unusual, in that, where there is a difference, other interventions commonly extend male life span more readily than female.<\/p>\n

MYC is a \u201ctranscription factor\u201d, which means it acts by turning other genes on and off. \u00a0In fact, MYC is one of the most powerful, broad-action transcription factors, with effects on the activities of thousands of other genes. \u00a0One hint about the mechanism of action is that reduced MYC leads to less active ribosomes, the organelles in which proteins are transcribed. \u00a0MYC+\/- animals have less of every kind of protein, and it is no longer surprising<\/a> that this leads to extended life span.<\/p>\n

MYC has been identified in the past<\/a> as an intermediary that is necessary to help turn on telomerase activity in response to caloric restriction and mimetics (drugs that act like CR). \u00a0The Brown team was encouraged to report that mice with half their MYC missing did not lack for telomerase.<\/p>\n

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What can be done for people who are unfortunate to have been born already with two copies of the MYC gene?<\/b><\/p>\n

That MYC is overexpressed in cancer cells has been known a long time. \u00a0Much of the work on MYC and how to turn it off has been done in the course of a search for effective \u00a0cancer treatments. \u00a0Peter Vogt\u2019s lab<\/a> at Scripps Inst in La Jolla has led this charge. \u00a0They have searched through thousands of small molecules, looking for chemicals that \u201cturn off\u201d MYC or interfere with its actions. \u00a0Here is a paper<\/a> that catalogs dozens of small molecules that have been studied for their ability to either stop MYC from being transcribed or inhibit the MYC protein from acting. \u00a0I was amused to note that the standard notion of a \u201csmall\u201d molecule extends to include a great deal of complexity. \u00a0The standard for \u201csmall\u201d is scaled by protein macromolecules that are fold from thousands of chained amino acids.<\/p>\n

\"MYC-inhibitors\"<\/a><\/p>\n

But the abundance of candidate molecules isn\u2019t necessarily good news. \u00a0It means that researchers have followed a well-worn path and pursued many candidate drugs, all with limited success for one reason or another.<\/p>\n

It is rare to discover death genes, pure and simple–genes that have no other purpose than to kill us. \u00a0Such genes are known (or suspected) in worms [ref<\/a>] but not humans. \u00a0But the list of genes that have been co-opted for programmed death is substantial. \u00a0I have reported some here last year<\/a>: TOR, NFk-B, IGF-1, wnt etc. \u00a0These genes are over-expressed, especially in old age, with consequences that are purely detrimental. \u00a0They make attractive targets for anti-aging therapy.<\/p>\n

In other words, death on a schedule\u00a0is programmed into our genes, but not with specific \u201ctime bomb\u201d genes. \u00a0Rather, the program works by co-opting\u00a0genes that have other uses early in life, but that are deployed for the purpose of self-destruction late in life. The classic example is inflammation, which is an important mechanism of defense, but which is loosed upon healthy cells, causing cancer and dementia late in life.<\/p>\n

So MYC is one of those genes without which we can’t live and\u00a0grow, but late in life it slips\u00a0its leash and causes great damage. \u00a0It might serve us well to keep MYC under tighter control,\u00a0if we can find a practical\u00a0means to do so.<\/p>\n

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I am grateful for this and many ideas to Reason over at FightAging! web site<\/a> and newsletter. \u00a0Week after week, he does a superb job of collecting and summarizing news and research in the field of anti-aging medicine. His viewpoint is a bit more mainstream than my own.* Readers of this page may be interested in subscribing<\/a>.<\/p>\n

In addition to MYC, this week\u2019s newsletter also includes<\/p>\n