Wel­come to the third edi­tion of Hour­glass, the monthly vir­tual gath­er­ing of blog­gers to dis­cuss the Biol­ogy of Aging.

For today’s edi­tion, let’s imag­ine all par­tic­i­pants sit­ting around a table lead­ing a lively Ques­tions & Answers ses­sion, dis­cussing as a group, lis­ten­ing, talk­ing. (And, well, aging.)

Q: What is aging?
Ms. Wikipedia: “Age­ing or aging (Amer­i­can Eng­lish) is the accu­mu­la­tion of changes in an organ­ism or object over time. Age­ing in humans refers to a mul­ti­di­men­sional process of phys­i­cal, psy­cho­log­i­cal, and social change. Some dimen­sions of age­ing grow and expand over time, while oth­ers decline. Reac­tion time, for exam­ple, may slow with age, while knowl­edge of world events and wis­dom may expand.”

Aging may not be the sex­i­est  of words in our vocab­u­lary. Unless, of course (as I heard some­where recently but can’t prop­erly credit), you con­sider the most com­mon alternative.

Q: If the objec­tive of anti-aging research is to extend lifes­pan, isn’t there a risk that we may neglect qual­ity of life. After all, would peo­ple really like to spend more years afflicted by the dis­eases and the decline that often come with age?
Ed (dragged to the dis­cus­sion by Chris and Alvaro): I have rel­a­tively good news to share. A recent Uni­ver­sity of South­ern Den­mark found that the pro­por­tion of elderly Danes who man­age to remain inde­pen­dent holds steady at about 30–35 per­cent between the ages of 90 to 100. This means that from society’s point of view, excep­tional long-life won’t lead to excep­tional lev­els of dis­abil­ity. This pat­tern seems con­sis­tant across dif­fer­ent lifespans.

Q: OK, so at least it is not all doom and gloom. Now, can we really expect we will one day be able to extend not only mean but max­i­mum lifes­pan?
Chris: well, poten­tially yes, but first of all we need to bet­ter  under­stand how pre­ma­ture aging resem­bles extended longevity, and the source of tran­scrip­tional change as we age, to mea­sure bio­log­i­cal age in a mean­ing­ful way. Given the obser­va­tion that expres­sion of gene X (or hor­mone Z) changes with age, one must next ask: How do we know whether this change reflects a causative fea­ture of aging, a defen­sive response to another age-related change, a pas­sive response of no great import, an epiphe­nom­e­non, or an arti­fact of the exper­i­men­tal system?.

Q: Let’s now dis­cuss the con­cept of “lifes­pan plas­tic­ity” and the sta­tus of the research today.
Jake (dragged too): Research on lab organ­isms such as yeast, worms and mice has encour­aged the notion that lifes­pan is plastic-this is, it can be extended. Nature just pub­lished a great review of anti-aging sci­ence, com­bin­ing cau­tious opti­mism with a call not to head down too quickly to the Nat­ural med­i­cine store for resver­a­trol in a pill, for exam­ple. Caloric-restriction, and some com­pounds, seem to influ­ence path­ways that reg­u­late over­all metab­o­lism, and have an impact on lifes­pan. How­ever, none of the drugs tested have shown lengthen life span in healthy rodents much less humans. we also don’t know whether inhibit­ing pro-aging path­ways in humans will have the same effect that it has in lower organ­isms. Fur­ther, we still have to fig­ure out how to dis­tin­guish between dis­ease and what is called intrin­sic aging — or aging not caused by disease.

Q: In short, there is much poten­tial, but more research needs to be done. Now, does exist­ing research sup­port spe­cific inter­ven­tion to expand Healthspan (not just lifes­pan, but lifes­pan in a healthy con­di­tion).
Ward: Exer­cise is an obvi­ous first step. A num­ber of stud­ies have shown how con­sis­tent car­dio­vas­cu­lar exer­cise can have mod­est effects on mean lifes­pan (usu­ally in the 8–12%) and also help main­tain func­tional abil­ity, there­fore con­tribut­ing to longer healthspan.

Q: We should also con­sider our Brain Healthspan. After all, “we” are a func­tion of our brains. Any­thing we can do there?
Adrian: exer­cise helps there too, both by help­ing main­tain cog­ni­tive func­tion and by pro­mot­ing neu­ro­ge­n­e­sis and neu­ron sur­vival.
Alvaro: the brain reserve the­ory adds light on the impor­tance of life­long men­tal stim­u­la­tion, but still need to bet­ter under­tand  the neu­ro­bi­ol­ogy of aging and cog­ni­tive decline. Let’s take a look at some of San­ti­ago Ramon y Cajal’s rec­ol­lec­tions of his life. On the one hand, was aware of the poten­tial for life­long neu­ro­plas­tic­ity. On the other, he could do lit­tle to pre­vent his own cog­ni­tive decline.

Q: Can food also play a role in main­tain­ing brain health as we age?
Pas­cale: For a great in-depth review of the effects of food on the brain you can check out Fer­nando Gomez-Pinilla’s recent arti­cle in Nature Reviews Neu­ro­science, dis­cussing the respec­tive mer­its of Omega-3 fatty acids, folic acid , flavonoids, antiox­i­dant foods. Please note that most of the stud­ies show­ing pos­i­tive effects of these nutri­ents have been con­ducted in mice.

Q: Let’s go back to the con­cept of expand­ing Healthspan. Are there pub­lic health impli­ca­tions
Liz: I’d say pre­vent­ing falls among the elderly — falls are a lead­ing cause of seri­ous injury and death among the U.S. elderly. Juer­gen Blu­dau, chief geri­a­tri­cian at the Brigham and Wom­ens Hos­pi­tal, says the med­ical com­mu­nity needs to do a bet­ter job sup­port qual­ity of life, by which he meant two things: as much free­dom from the rav­ages of dis­ease as pos­si­ble, and the reten­tion of enough func­tion for active engage­ment in the world.

Q: Let’s explore future direc­tions for research in the area. What’s the recent deal with autophagy?
Rea­son: You might think of autophagy as a form of self-maintenance for your cells: it is the destruc­tion of dam­aged and older cel­lu­lar com­po­nents such that newly built com­po­nents can take their place. You may expect to see some autophagy-enhancing drugs appear in the next years, once we bet­ter under­stand, for exam­ple, how to manip­u­late the tumor sup­pres­sor pro­tein p53, which has a major impact on organ­is­mal aging.

Q: Other inter­est­ing areas?
Abel: I’d sug­gest pay atten­tion to the prop­er­ties of mus­ca­dine skin extract . Some com­pa­nies are in fact already sell­ing those as dietary sup­ple­ments (i.e., prod­ucts not eval­u­ated by the FDA for either effec­tive­ness or safety), despite weak evi­dence.
Laura: we also need to pay more atten­tion to neu­rode­gen­er­a­tive dis­or­der such as Mul­ti­ple Sys­tem Atro­phy (MSA), a rare spo­radic dis­ease with aver­age age of onset at 59 years (+/- 7), and aver­age dura­tion being 7 years.

Q: Fun discussion…but we need to wrap up now. Any vol­un­teer to pro­vide some final words of wis­dom before we go back to our busy daily lives?
Anne: Let’s remem­ber, Exis­tence is won­der­ful. I look for­ward to learn­ing more of what such crea­tures as mole-rats and echid­nas may be able to teach us about them­selves, about aging, and about the curi­ous inter­play between metab­o­lism, chem­istry, activ­ity, and all the other processes that make life possible.

Thank you all for your par­tic­i­pa­tion. Please remem­ber that Hour­glass IV will appear on Octo­ber 14th at Exis­tence is Won­der­ful.

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