Are cell membranes the pacemakers of metabolism?

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One of the earliest observations in gerontology was the correlation of increased size with a longer lifespan. Presumably, being large makes one less prone to predators and allows better coping to starvation thereby decreasing your extrinsic mortality rate. At the same time, metabolic rate decreases when size increases and this could lower the extent of inevitable oxidative damage. This is known as the rate of living theory.

When comparing species among themselves, size mostly correlates with longevity. Yet a couple of exceptions like bats, birds and naked mole rats are able to survive much longer than expected given their size and increased metabolic rate.

Such exceptions have astonished researchers for years. Until a connection was made between the composition of cell membranes and the longevity of species. The animal cell membrane is actually a double layer of fats or lipids. Fatty acids count among the components of fats. They belong to one of the following three categories:

  • saturated fatty acids

  • polyunsaturated fatty acids

  • monounsaturated fatty acids

Fat which is solid at room temperature is mostly saturated. The degree of fat unsaturation provides fluidity at room temperature because unsaturated fatty acids have a lower melting point compared to saturated ones.

The structure of fatty acids is largely dependent on temperature.

According to their structure, fats fall on a certain value of the peroxidation index which measures their susceptibility of being oxidatively damaged. Saturated and monounsaturated fatty acids are mostly resistant to peroxidation, while polyunsaturated ones get easily damaged. Several end products of lipid peroxidation can further damage the cell membrane. Consequently, the proteins inhabiting the cell membrane will not undergo their normal functions and the permeability of the cell will vary. Being too lax about which substances enter the cell is just as damaging as being too restrictive and not allowing certain substances such as hormones from accomplishing their tasks.

The permeability of cells and their organelles is determined by modulating the balance between saturated and unsaturated fatty acids. In biology, this is known as homeoviscous adaptation. The strategy is especially important in poikilothermic organisms which can’t regulate their own inner core temperature. Hence when temperatures drop, cell permeability is increased by maintaining a larger proportion of unsaturated fatty acids. When temperatures increase, saturated fatty acids dominate the picture.

The composition of cell membranes varies wildly among species and this may underlie their different metabolic rates. The cell membranes of long-lived species are more resistant to peroxidation compared to shorter-lived ones. When it comes to mammals, body mass increases correlate with a decrease in polyunsaturated fatty acids in cell membranes.

The cell membranes of birds are more resistant to peroxidation compared to similarly-sized mammals. Such differences exist between queens and their workers in eusocial insects despite starting out with the same maternal genome. All these may explain the longevity of organisms which don’t fit the rate of living theory.

You may be wondering whether the type of fatty acids in the diet has any influence over the fatty acids in your cell membranes. As far as I know, nobody proved this taking place in humans. But the differences between bee workers and bee queens when it comes to peroxidation and lifespan differences despite starting out with the same genome makes me think their diet has a lot to do with their differential gene expression. And as far as temperature goes, homeoviscous adaptation is not that important in a species like us where individuals are able to regulate their inner core body temperature.

 

Cited studies include:

Haddad, L. S., L. Kelbert, and A. J. Hulbert. “Extended Longevity of Queen Honey Bees Compared to Workers is Associated with Peroxidation-resistant Membranes.” Exp Gerontology 42, no. 7 (July 2007): 601-9. doi:10.1016/j.exger.2007.02.008.

Hulbert, A. J., R. Pamplona, R. Buffenstein, and W. A. Buttemer. “Life and Death: Metabolic Rate, Membrane Composition, and Life Span of Animals.” Physiological Reviews 87, no. 4 (October 2007): 1175-213. doi:10.1152/physrev.00047.2006.

Sinensky, M. “Homeoviscous adaptation–a homeostatic process that regulates the viscosity of membrane lipids in Escherichia coli.” Proc Natl Acad Sci 71, no. 2 (February 1974): 522-525. doi:10.1073/pnas.71.2.522.

Note: this blog post includes excerpts from ‘The aging gap between species‘ book.

 

Anca Ioviţă is the author of Eat Less Live Longer: Your Practical Guide to Calorie Restriction with Optimal Nutrition ,The Aging Gap Between Species and What Is Your Legacy? 101Ways on Getting Started to Create and Build One available on Amazon and several other places. If you enjoyed this article, don’t forget to sign up to receive updates on longevity news and novel book projects!

Don’t miss out on the Pinterest board on calorie restriction with optimal nutrition where she pins new recipes every day.
https://www.pinterest.com/longevityletter/eat-less-live-longer/
Or the Comparative Gerontology Facebook Group where you can join the discussions on how species age at different speeds and what could be the mechanisms underlining these differences!
https://www.facebook.com/groups/683953735071847/

 

Books

 

 

 

Eat less, live longer – your practical guide to calorie restriction with optimal nutrition

Eat less, live longer – your practical guide to calorie restriction with optimal nutrition

There is a fine line separating calorie restriction with optimal nutrition from starvation. Don’t cross it. Read this book instead.

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Aging is a puzzle to solve.
Lifespans among species vary wildly.
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Find out today.

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Al terzo anno di medicina mi sono imbattuta in un articolo in Rete che parlava della restrizione delle calorie con nutrizione ottimale. Si parlava di un intervento apparentemente semplice, fatto sul regime alimentare di alcuni organismi e animali da laboratorio che ne aveva prolungato le aspettative di vita media e massima: lieviti, moscerini della frutta, vermi, topi. Ad essere sincera, avevo liquidato l’esperimento come una stranezza: poteva anche aver avuto efficacia su organismi semplici come i moscerini della frutta, ma non avrebbe mai funzionato su esseri viventi complessi come noi: troppo bello per essere vero.
Il tempo mi ha dato torto: leggere teorie legate all’invecchiamento è una cosa, prendersi cura tutti i giorni di persone che hanno tre o quattro volte la tua età è un’altra. Così, ho semplicemente fatto due più due.Avevo notato che alcune delle persone delle quali mi occupavo quotidianamente erano invecchiate “come un buon vino”, altre come “vino divenuto aceto”. Basandomi sulla loro esile struttura fisica e sui dettagli della loro vita, sembrava proprio che l’assunzione di calorie c’entrasse in qualche modo. È stato così che ho iniziato a scrivere le prime righe di questo libro.

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Eet Minder Leef Langer – ‘n Gids Vir Kalorie Beperking Met Optimale Voeding

Tydens my derde jaar in die mediese skool, het ek op ‘n aanlyn artikel afgekom oor kalorie beperking met optimale voeding. Ek het gelees oor ‘n oënskynlik eenvoudige dieët ingryping wat die gemiddelde en maksimale lewensduur van laboratorium diere soos gis, vrugte vlieë, wurms en muise verleng het. Op daardie tydstip was ek nie bewus dat sulke eksperimente reeds gedoen word op nie-menslike primate ook nie.

Eerlikwaar, ek het afgemaak as nuuskierigheid, ‘n ingryping wat ‘n effek het op eenvoudige organismes soos vrugte vlieë, maar wat nooit op sulke komplekse wesens soos ons sal werk nie. Dit was net te goed om waar te wees.

Tyd het verby gegaan en my verkeerd bewys. Gegewe ‘n vroeë kindertyd fassinasie met die grense van lewens verlenging, het ek ingenieurswese en medisyne gestudeer in ‘n poging om radikale verlengde menslike lewensduur te bewerkstellig. Na ‘n kort rukkie van navorsing oor neurale prostese in ‘n Duitse laboratorium, het ek besef dat kunsmatig ingeplante toestelle binne in die menslike liggaam nie ‘n lang termyn oplossing was nie.

Ek het huis toe gekom waar ek met my mediese residensie in geriatries begin het, die tak van medisyne wat spesialiseer in ouderdom-geassosieerde siektes. ‘n Snaakse ding het toe gebeur. Om te lees oor teorieë van oud word is een ding. Daaglikse sorg vir mense 3 – 4 keer jou ouderdom is totaal ‘n ander ding en ek het begin om die kolletjies te verbind.

Ek het opgelet dat sommige mense verouder soos wyn en ander soos asyn. Volgens hulle maer liggaamstrukture en gedetailleerde lewens stories, het dit gelyk asof kalorie inname iets daarmee te doen gehad het. Dis hoe ek die eerste woorde van hierdie boek begin tik het.

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Pour être honnête, j’ai vu cette intervention comme une simple anecdote qui pourrait avoir quelques effets sur des organismes simples tels que des moches drosophiles, mais également comme quelque chose qui ne pourrait jamais fonctionner pour des organismes complexes comme nous. Cela paraissait trop beau pour être vrai.

Avec le temps, je me suis rendue compte que j’avais tort. Pour satisfaire ma fascination d’enfant sur les limites de l’extension de la vie, j’ai étudié l’ingénierie et la médecine, pour tenter de trouver un moyen d’allonger la durée de vie des êtres humains. Après un court séjour dans le domaine des prothèses neuronales dans un laboratoire allemand, j’ai réalisé que l’implantation d’appareils artificiels dans le corps humain n’était pas une solution pérenne.

Je suis retournée chez moi et j’ai entamé mon internat en médecine gériatrique, la branche de la médecine spécialisée dans les maladies liées à l’âge. C’est là qu’un événement cocasse s’est produit. Lire les différentes théories sur le vieillissement est une chose. Mais s’occuper de personnes trois à quatre fois plus âgées que vous en est une autre, et c’est là que j’ai commencé à faire le lien.

J’ai remarqué que certaines personnes vieillissaient comme un bon vin, tandis que d’autres connaissaient un vieillissement plus proche de celui du vinaigre. Leurs corps fragiles et leurs histoires de vie détaillées semblaient indiquer que l’apport calorique y était pour quelque chose. C’est ce qui m’a poussé à écrire les premiers mots de ce livre.

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Honestamente, acabei descartando isso como curiosidade. Uma intervenção que poderia ter algum efeito em organismos simples, como moscas de frutas, mas algo que nunca funcionaria em seres complexos como nós. Parecia bom demais para ser verdade.

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Voltei para casa, onde comecei minha residência médica em geriatria, a área da medicina especializada em doenças associadas à idade. Algo engraçado acabou acontecendo. Ler sobre as teorias do envelhecimento é uma coisa. Cuidar diariamente de pessoas com 3 ou 4 vezes a sua idade, é outra completamente diferente e eu comecei a ligar os pontos.

Eu notei que algumas pessoas envelheciam como vinho e outras envelheciam como vinagre. De acordo com seus corpos magros e históricos detalhados, parecia que a ingestão de calorias tinha algo a ver com isso. Foi assim que comecei a digitar as primeiras palavras deste livro.

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Avete mai prestato attenzione al processo di metamorfosi di una farfalla? L’uscita dalla crisalide è un momento difficile e doloso. Potreste pensare di farle un favore tagliandone la parte superiore per agevolare la sua fuoriuscita da essa, ma se lo farete, le ali della farfalla non si svilupperanno propriamente e resterà menomata per il resto della sua vita. Sfide e sacrifici sono necessari perché la metamorfosi abbia luogo e sono allo stesso modo necessari anche per creare e costruire un’eredità.

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