Negligibly Senescent Species in the Context of Longevity Science

This popular science article focuses on the study of negligibly senescent species in the context of work aimed at adjusting the course of human aging. There is at least one negligibly senescent mammal, the naked mole-rat, but it seems to me that attempting to mine benefits from other species and port them to humans is just another way to say we should re-engineer human metabolism to age more slowly. The past twenty years have demonstrated that this is enormously expensive and enormously challenging. Billions have been spent on trying to safely change just a few genes and proteins, and to try to better understand the modestly slowed aging of calorie restriction, with no practical result other than to add thin slices to our knowledge of metabolic processes. We should have similar expectations for the results of trying to obtain benefits from the biochemistry of another species - and going far beyond that in scope to produce a whole new human metabolism is very far from being a plausible project today.

The only way today to make practice, cost-effective progress towards very large gains in human longevity is to follow the SENS model of damage repair. The damage that causes aging is very well understood, and we don't need a full explanation of how exactly at the detail level that damage multiplies and interacts to contribute to every facet of aging. We don't need to adjust those facets or integrate them into a new working model of human biochemistry. All we have to do is periodically repair the damage, maintaining the youthful version of human biochemistry that we know works. It is an engineering approach in which we can bypass our ignorance of the details in order to produce working rejuvenation therapies here and now. Repair of the first form of damage is already in the clinical development pipeline: clearance of senescent cells. Others might follow soon, if there was just more support and funding.

The naked mole rat is the superhero of the animal kingdom. Similarly sized rodents usually live for about five years. The naked mole rat lives for 30. Even into their late 20s, they hardly seem to age, remaining fit and healthy with robust heartbeats, strong bones, sharp minds, and high fertility. They don't seem to feel pain and, unlike other mammals, they almost never get cancer. "It's not a ridiculous exaggeration to suggest we can one day manipulate our own biochemical and metabolic pathways with drugs or gene therapies to emulate those that keep the naked mole rat alive and healthy for so long. In fact, the naked mole rat provides us the perfect model for human aging research across the board, from the way it resists cancer to the way its social systems prolong its life."

Over the centuries a long line of optimists, alchemists, hawkers and pop stars have hunted various methods of postponing death, from drinking elixirs of youth to sleeping in hyperbaric chambers. The one thing those people have in common is that all of them are dead. Still, the anti-aging industry is bigger than ever. In 2013, its global market generated more than $216 billion. By 2018 it will hit $311 billion, thanks mostly to huge investment from Silicon Valley billionaires and Russian oligarchs who've realized the only way they could possibly spend all their money is by living forever. Even Google wants in on the action, with Calico, its $1.5 billion life-extension research center whose brief is to reverse-engineer the biology that makes us old or, as Time magazine put it, to "cure death." It's a snowballing market that some are branding "the internet of healthcare." But on whom are these savvy entrepreneurs placing their bets? After all, the race for immortality has a wide field.

British biomedical gerontologist Aubrey de Grey is enjoying the growing clamor about conquering aging, or "senescence," as he calls it. His charity, the SENS Research Foundation, has enjoyed a bumper few years thanks to a $600,000-a-year investment from Peter Thiel ("Probably the most extreme form of inequality is between people who are alive and people who are dead"). Though he says the foundation's $5.75 million annual budget can still "struggle" to support its growing workload. According to de Grey, the fundamental knowledge needed to develop effective anti-aging therapies already exists. He argues that the seven biochemical processes that cause the damage which accumulates during old age have been discovered, and if we can counter them we can, in theory, halt the ageing process. He says traditional medicines won't wind back the hands of our body clocks - we need to manipulate our makeup on a cellular level, like using bacterial enzymes to flush out molecular "garbage" that accumulates in the body, or tinkering with our genetic coding to prevent the growth of cancers, or any other disease. "If you look at the maths it is very straightforward. All we are saying here is that it's quite likely that within the next 20 or 30 years, we will develop medicines that can rejuvenate people faster than time is passing. It's not perfect yet, but soon we'll take someone aged 60 and fix them up well enough that they won't be 60 again, biologically, for another 30 years. In that period, therapies will improve such that we'll be able to rejuvenate them again so they won't be 60 for a third time until they are chronologically 150, and so on. If we can stay one step ahead of the problem, people won't die of aging anymore."

Of course, the naked mole rat isn't the only animal scientists are probing to pick the lock of long life. With a heart rate of 1,000 beats a minute, the tiny hummingbird should be riddled with rogue free radicals, the oxygen-based chemicals that contribute to aging by gradually destroying DNA, proteins, and fat molecules... but it's not. Then there are pearl mussel larvae that live in the gills of Atlantic salmon and mop up free radicals, and lobsters, which seem to have evolved to have more of a protein which repairs the tips of DNA, allowing for more cell divisions than most animals are capable of. And we mustn't forget the 2mm-long C. elegans roundworm. Within these 2mm-long nematodes are genetic mechanisms that can be picked apart like cogs and springs in an attempt to better understand the causes of aging and ultimately death.



Hi all, very interesting NMRs are full of surprises. I am very intrigued about that special parasite (pearl mussel larvae) in the Atlantic salmon's gills that makes it live for 13 years (surpassing the other fast dying salmons) and halts its senescence via delaying the degeneration of its brain endocrinal system (altering hormones and IGF-1 basically) thus improving oxidative stress resistance.

"Like immortality?" I ask. Dr. De Grey sighs: "That word is the bane of my life. People who use that word are essentially making fun of what we do, as if to maintain an emotional distance from it so as not to get their hopes up. I don't work on 'curing death,' I work on keeping people healthy. And, yes, I understand that success in my work could translate into an important side effect of people living longer. But to 'cure death' implies the elimination of all causes, including, say, dying in car accidents. And I don't think there's much we could do to survive an asteroid apocalypse."

So instead, De Grey focuses on the things we can avoid dying from, like hypertension, cancer, Alzeimer's and other age-related illnesses. His goal is not immortality, but "radical life extension."

''"Like immortality?" I ask. Dr. De Grey sighs: "That word is the bane of my life. People who use that word are essentially making fun of what we do, as if to maintain an emotional distance from it so as not to get their hopes up. I don't work on 'curing death,' I work on keeping people healthy.''

I'm saddened but I also understand Aubrey's desperation/point (he had to defend himself and his credibility)...that word, immortality, may be plagued with ridicule, exaggeration, demonization, utter impossibility, unseriousness, condescending, mocquery and quack/snake oïl feel. I don't think everyone who uses the word immortality is wrong though, some are very well-intentioned and they mean it 'straight-face' value like the word's meaning, ''Eternal life''.
I understand he is trying to not make anyone have hopes too high, since a word like immortality is the highest there is and would be catastrophic on everyone's hopes if isn't reached. So, he prefers play it safe, protect the scientific validity/proof of his claims and; himself, altogether.
At least, he aims for keeping people healthy. And, just like the debate he had, he does not want to talk about stopping death, but about keeping people healthy longest - which would have an effect of them not dying, and possibly, if repeated, could thus become immortal (I shouldn't use this word...but what other words...Eternal/Living forever/living extremely).

Adg: ''...In that period, therapies will improve such that we'll be able to rejuvenate them again so they won't be 60 for a third time until they are chronologically 150, and so on. If we can stay one step ahead of the problem, people won't die of aging anymore."''

He is aiming more towards going above MLSP 122 years,

''...until they are chronologically 150, and so on.''

not the talk of ''there is a human alive or born soon who will live to a 1000 years'' which is his LEV.

I guess he meant if LEV is reached, but his estimâtes are more modest and if everything goes as planned we could reach 150 years old...less the 1000 years old (since you can die of a random outside accident (not of aging) during that time). IT could be possible if like he says (his LEV) :

''If we can stay one step ahead of the problem, people won't die of aging anymore."''

[A paradox of a parasite prolonging the life of its host. Pearl mussel can cancel the accelerated aging program in salmon].


Posted by: CANanonymity at May 11th, 2016 2:08 PM

That pearl mussel article is fascinating, CAN. Do you know if there are any more studies on the topic? A cursory google search has failed me, but I'm surprised there hasn't been more done because it seems like a crazy finding.

Posted by: James O'Donnell at May 16th, 2016 2:54 PM

@James O'Donnell

Hi James!

Check out this study, it is the same as the parasited salmon but instead, in a nematode (S.ratti) like C.elegans. This study shows free-living S.ratti and parasited S.ratti nematodes; and the kicker is the free-living S.ratti ones live a maximum lifespan of 5 days, whereas the parasited oned live 400 days maximum lifespan; which is a 80-fold extension of lifespan.
This is the same effect as the salmon living 3-4 years (senescence onset), and up to 13 years once parasited. But the most important element of this study is that it shows that Aubrey de Grey's LEV (Longevity Escape Velocity) paper is very true and a 1000-year lifespan (or even eternal life) is True, if we make IMR (initial mortality rate) completely null and MRDT (mortality rate of doubling time) exponentially increased. It made obvious sense that as specie individual post-pones mortality it would allow eternal life, but that's only 'on paper' theory; since we don't know what happens after maximum lifespan is surpassed in humans. This study, which measure IMR and MRDT in S.ratti, demonstrates there is no 'specie' maximum lifespan and shows/follows demographic senescence shift in a real live specie over time; and we can extrapolate it to humans too. It tells us that, indeed, humans can live way above 120 years old, only if IMR and MRDT are controlled; and SENS's LEV allows that. Maximum lifespan is just an estimate of the specie's 'known' maximum life expectancy is. If SENS makes all 7 therapies, reduces all types of damages to comprehensive 'enough' levels (to escape from 'damage' accrual of older age by restoring true biological youth health), then aging mechanism can be pushed-back 'for later' infinitely, in a repetitive fashion (play, rewind, play, rewind...loop, you never get to the end of the movie (death) like the 'Groundhog Day movie' with Bill Murray where the 'same' day always restarts anew the next day, so you live your friday for the rest of your life and the 6 other days don't exist anymore, only thing, it's always the 'same friday' you relive frozen in time) and mortality is nullified - totally (death becomes null and immortality/eternal life possible).

What is important about this study, is that mortality and oxidative stress/redox are 100% correlated and causated one another. Meaning that salmon that lives for 13 years once parasited and, obviously, has much reduced mortality than the 3-year old regular progeric-salmon; has complex Redox shifts Inside of it that alter brain endocrinology towards maintenaince of resources on somatic rather than sexual/reproduction resources. Demonstrating that sexual resources or not, somatic resources must be maintained. And one of the key change is changes in the redox (the reductive/oxidative antioxidative systems of the cell (Nrf2, Glutathione, Glutathione reductase, Peroxidase, Plasma membrane redox system, mitochondrial glutathione, cytosolic glutathione, Catalase, SOD, Coenzyme Q/Ubiquinol, and all of these ROS scavenging systems) that primes the cell for oxidative 'stress resistance'. Plus, this study shows that lipofuscin is almost absent in the parasited nematode, same for salmon..and for any specie that lives much longer. Lipofuscin correlates to specie (anomalous) 'maximum lifespan' and is a universal aging pigment biomarker, even in humans who accumulate it in every organ with age and correlates with our current biological age.

Strongyloides ratti: A Nematode with Extraordinary Plasticty in Aging


Posted by: CANanonymity at May 18th, 2016 6:00 PM

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