Interventions to Slow Aging in Humans: Are We Ready?

The more conservative end of the aging research community is not in favor of engineering approaches like SENS, which focus on repair of the known causes of aging as a way to evade very slow and expensive investigations of the details of how aging progresses, where understanding is still minimal and the unexplored spaces on the map remain very large. Engineering is a matter of doing the best you can in advance of full understanding, and can be highly effective. The Romans built great bridges without modern materials science and architectural understanding, for example. The conservative scientific viewpoint is to require something much closer to full understanding before progressing any further, however.

In the pure science view the only viable way forward to treat aging is to indeed follow the very slow and expensive process of obtaining full understanding of all the relevant complexity of our metabolism, followed by attempting to manipulate the operation of metabolism so as to slightly slow the aging process. Scientists putting forward this position avoid the claim that adding decades to human life spans is possible within the foreseeable future. Some don't believe it to be the case, others are merely not going to say so in public. The wheels turn slowly enough in the sciences that it has taken the better part of fifteen years to even come to the point of generally agreeing in print that gently slowing down the process of degenerative aging is possible and desirable.

All of this is why we need greater support for engineering approaches to the treatment of aging, such as the SENS research programs carried out by the SENS Research Foundation. If we wait around for the pure science community to catch up to what is plausible and worth trying, we'll all be aged and dead before there is significant progress. It is much better to forge ahead and build proposed rejuvenation therapies based on a reasonable expectation of providing benefits than to continue the slow and steady path. None of the approaches discussed in the paper below are capable in principle of providing more than a fraction of the additional years of healthy life span that a prototype rejuvenation toolkit based on SENS programs could in theory produce. They will further be of very limited use in old people: they don't repair the damage causing degeneration and disease, but only slow down the pace at which it continues to accumulate.

Human aging and age-associated diseases are emerging as among the greatest challenges and financial burdens faced by developed and developing countries. Research related to longevity extension has traditionally been viewed with skepticism and with concerns that it could lead to an increase in the size of the elderly population and the prevalence of diseases associated with aging. However, studies in a wide range of organisms have demonstrated that major lifespan extension is accompanied by reduced or delayed morbidity in most cases.

There was a general consensus among this panel of experts on the following points: (i) aging can be slowed by many interventions; (ii) slowing aging typically delays or prevents a range of chronic diseases of old age; (iii) dietary, nutraceutical, and pharmacologic interventions that modulate relevant intracellular signaling pathways and can be considered for human intervention have been identified. Additional potential targets will continue to emerge as research progresses; and (iv) it is now necessary to cautiously proceed to test these interventions in humans.

The strategies believed to be most promising by the panel of invited experts and authors of this manuscript are as follows: (1) Pharmacological inhibition of the GH/IGF-1 axis, (2) Protein restriction and Fasting Mimicking Diets, (3) Pharmacological inhibition of the TOR-S6K pathway, (4) Pharmacological regulation of certain sirtuin proteins and the use of spermidine and other epigenetic modulators, (5), Pharmacological inhibition of inflammation, (6) Chronic metformin use. These choices were based in part on: (i) consistent evidence for their pro-longevity effects in simple model organisms and rodents; (ii) evidence for their ability to prevent or delay multiple age-related diseases and conditions; and/or (iii) clinical evidence for their safety in small mammals and/or nonhuman primates.

Accumulating scientific evidence from studies conducted in various organisms and species suggests that targeting aging will not just postpone chronic diseases but also prevent multiple age-associated metabolic alterations while extending healthy lifespan. A number of pathways affecting metabolism, growth, inflammation, and epigenetic modifications that alter the rate of aging and incidence of age-related diseases have been identified. Interventions with the potential to target these pathways safely and to induce protective and rejuvenating responses that increase human healthspan are becoming available. We believe that the time has come not only to consider several therapeutic options for the treatment of age-related comorbidities, but to initiate clinical trials with the ultimate goal of increasing the healthspan (and perhaps longevity) of human populations, while respecting the guiding principle of physicians primum non nocere.

Link: http://onlinelibrary.wiley.com/enhanced/doi/10.1111/acel.12338/

Comments

Weird that they don't mention senescent cell removal given that the recent demonstrations in mice used drugs already tested in humans. I'm just guessing, but senescent cell removal by itself could do more than any of the proposed interventions listed.

Posted by: Jim at April 27th, 2015 8:47 AM

They do mention it.

"Possible strategies to target them include elimination of senescent cells (e.g., by NK cell activation)(Tchkonia et al., 2013), "

Posted by: Slicer at April 27th, 2015 9:44 AM

So they had a meeting in 2013 and its taken them till now to conclude that they possibly, maybe should perhaps cautiously start testing in human and just maybe do something about it?

I don't often use the phrase but seriously LOL

I am also surprised they didn't add Telomere rejuvenation and Stem cell replacement (REPLINISENS) to the priority list.

Posted by: Steve H at April 28th, 2015 2:36 AM

I hoped that the new medicine to take control after the reading of the human genome in 2003. The change is so great that we can say without error that just now we know how diseases occur, as are prevented and as cured. Is a clear need to slow aging by any means and even better, start as soon as possible engineering type intervention to that effect. I think the meeting in Italy from 2013 to achieve consensus on treatments anti-aging processes, it is the way to go: we have to advertise that there are some ways to act to help a good diet and physical activity, as is fasting intermittent and resveratrol, to name a few things. Of course this will be improved ... but meanwhile, you already have something to start.

Posted by: eduardo at May 2nd, 2015 9:21 AM

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