Redesigning People: Want to be BETTER as You Age?

Healthy Life Extension

Funding Aging Research

Redesigning People: Want to be BETTER as You Age?

posted on March 20th, 2012

Dear Future Centenarian,

Enhancements, artificial body parts and some technological helping hands are already here. In the future, parts of you that you now consider you may me manufactured in various parts of the world. Exoskeletons are one somewhat crude¦ but amazing example.

Some of these were originally developed to help soldiers become more efficient. Others were developed to fix soldiers who were lucky enough to not have been killed”but unlucky enough to have been maimed. Soon, these breakthrough technologies will make us better than the original¦ and certainly better than the aged.

The exoskeleton manufactured by Ekso Bionics in Berkeley, California,  is one harbinger of what™s coming in the next decade or two to treat the injured and the ill with radical new technologies, as reported in

In a few more years, you might be wearing your own eLEGS to carry heavy loads around the house, or as a soldier on patrol in some distant corner of the world (assuming we aren™t using only drones). Flash forward a few more years, and you may have the option of permanently implanting in your legs the œeLEGS LXII, an endo-skeletal implant that stays with you like a futuristic hip or knee implant does today.

Other portents include first-generation machines and treatments that range from deep brain implants that can stop epileptic seizures to stem cells that scientists are using experimentally to repair damaged retinas.

Which leads us to the crucial question for the approaching age of human enhancement: How far would you go to modify yourself using the latest medtech?

Would you replace perfectly good legs with artificial ones if they made you faster and stronger?

Would you take a daily pill that not only stimulated your brain to help you do your best on a test, but also bumped up your memory?

Would you sign up for a genetic alteration that would make you taller and stronger?.

These are interesting questions that we WILL be faced with someday. I for one am already exploring the Ekso option. Will you be next?

Thanks to rapidly emerging technologies, the blind shall see, the deaf will hear, and the lame will walk. In fact, we may see, hear and walk better than ever before.

Long Life,
David Kekich


Just as physical exercise is beneficial, so too is exercising the mind. This open access paper examines structured mental exercise as a basis for therapy that might do at least some good for neurodegenerative disease patients: "Non-pharmacological intervention of memory difficulties in healthy older adults, as well as those with brain damage and neurodegenerative disorders, has gained much attention in recent years.

The two main reasons that explain this growing interest in memory rehabilitation are the limited efficacy of current drug therapies and the plasticity of the human central nervous system and the discovery that during aging, the connections in the brain are not fixed but retain the capacity to change with learning. Moreover, several studies have reported enhanced cognitive performance in patients with neurological disease, following non-invasive brain stimulation [i.e., repetitive transcranial magnetic stimulation and transcranial direct current stimulation to specific cortical areas].

The present review provides an overview of memory rehabilitation in individuals with mild cognitive impairment and in patients with Alzheimer's disease with particular regard to cognitive rehabilitation interventions focused on memory and non-invasive brain stimulation. Reviewed data suggest that in patients with memory deficits, memory intervention therapy could lead to performance improvements in memory, nevertheless further studies need to be conducted in order to establish the real value of this approach."

Less fat tissue is unambiguously good for you over the long term, and one side effect of calorie restriction is the loss of excess fat tissue - but that is only a side effect. More interesting stuff is going on at the level of cells and their mechanisms: "Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue:

White adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis [was] performed on both WAT and BAT from nine month old male rats fed ad libitum or subjected to CR for six months. Our findings suggest that CR activates mitochondrial energy metabolism and fatty acid biosynthesis in WAT. It is likely that in CR animals WAT functions as an energy transducer from glucose to energy-dense lipid. In contrast, in BAT CR either had no effect on, or down-regulated, the mitochondrial electron transport chain, but enhanced fatty acid biosynthesis.

This suggests that in CR animals BAT may change its function from an energy consuming system to an energy reservoir system. Based on our findings, we conclude that WAT and BAT cooperate to use energy effectively via a differential response of mitochondrial function to CR." It is worth noting that there are other signs that the biochemistry of fat tissue, and its effects on health, can be dramatically altered - see the research on fat in GHRKO mice, for example.

Here is a study claiming a noticeable impact on mortality rates from eating red meat. Weight is considered to some degree via body mass index, but I have to wonder if this only reflects a modest association of red meat consumption with other, less healthy lifestyle choices rather than an actual red-meat-based mechanism - as an obvious candidate mechanism for that isn't also present in all meat consumption isn't springing to mind: researchers "found that red meat consumption is associated with an increased risk of total, cardiovascular, and cancer mortality. The results also showed that substituting other healthy protein sources, such as fish, poultry, nuts, and legumes, was associated with a lower risk of mortality.

[Researchers] observed 37,698 men from the Health Professionals Follow-up Study for up to 22 years and 83,644 women in the Nurses' Health Study for up to 28 years who were free of cardiovascular disease (CVD) and cancer at baseline. Diets were assessed through questionnaires every four years. One daily serving of unprocessed red meat (about the size of a deck of cards) was associated with a 13% increased risk of mortality, and one daily serving of processed red meat (one hot dog or two slices of bacon) was associated with a 20% increased risk.

These analyses took into account chronic disease risk factors such as age, body mass index, physical activity, family history of heart disease, or major cancers. Replacing one serving of total red meat with one serving of a healthy protein source was associated with a lower mortality risk: 7% for fish, 14% for poultry, 19% for nuts, 10% for legumes, 10% for low-fat dairy products, and 14% for whole grains. The researchers estimated that 9.3% of deaths in men and 7.6% in women could have been prevented at the end of the follow-up if all the participants had consumed less than 0.5 servings per day of red meat."

NOTE: I wonder what the study would have shown if the subjects ate free-range red meat instead of commercial meat.

A therapy that can robustly correct any mitochondrial DNA mutation throughout the body can be turned into a way to rejuvenate the stochastic damage of aging that occurs to the thirteen important mitochondrial genes not replicated in the cell nucleus. If asked to wager, based on the evidence I'd suggest that mitochondrial damage is the largest individual contribution to aging, which is why it's important to see progress on fixing it or making it irrelevant.

So this, I think, is a development worth watching: "Researchers [have] identified, for the first time, a generic way to correct mutations in human mitochondrial DNA by targeting corrective RNAs. I think this is a finding that could change the field. We've been looking to do this for a long time and we had a very reasoned approach, but some key steps were missing. Now we have developed this method and the next step is to show that what we can do in human cell lines with mutant mitochondria can translate into animal models and, ultimately, into humans.

Gene therapy is often used to express proteins that can treat the cause of a variety of diseases. In this case, [researchers] developed a strategy to target and import specific RNA molecules encoded in the nucleus into the mitochondria and, once there, to express proteins needed to repair mitochondrial gene mutations. First, the research team had to figure out a way to stabilize the reparative RNA so that it was transported out of the nucleus and then localized to the mitochondrial outer membrane. This was accomplished by engineering an export sequence to direct the RNA to the mitochondrion.

Once the RNA was in the vicinity of the transport machinery on the mitochondrial surface, then a second transport sequence was required to direct the RNA into the targeted organelle. With these two modifications, a broad spectrum of RNAs were targeted to and imported into the mitochondria, where they functioned to repair defects in mitochondrial respiration and energy production in two different cell line models of human mitochondrial disease. This study indicates that a wide range of RNAs can be targeted to mitochondria by appending a targeting sequence with or without a mitochondrial localization sequence, to provide an exciting, general approach for overcoming mitochondrial genetic disorders."

Heat shock proteins (HSPs) are important in cellular housekeeping, the processes of removing and repairing damage - and given how important these processes are to longevity, it's no surprise that we see associations between HSP levels and longevity. Researchers have been investigating how to build therapies based on boosting HSPs in recent years, but here is a different point of view: research to show that insulin resistance reduces HSP levels, which may be another one of the ways in which being fat and sedentary enough to become insulin resistant harms your health:

"Heat shock protein (HSP)70 decreases with age. Often aging is associated with coincident insulin resistance and higher blood glucose levels, which also associate with lower HSP70. We aimed to understand how these factors interrelate through a series of experiments using vervet monkeys (Chlorocebus aethiops sabaeous). Monkeys fed low-fat diets showed no association of muscle HSP70 with age, but levels were highly heritable. Insulin resistance was induced in vervet monkeys with high-fat diets, and muscle biopsies were taken after 0.3 or 6 years.

HSP70 levels were significantly greater after 0.3 years but were significantly lower following 6 years of high-fat diet. Associations with glucose also switched from being positive to strikingly negative with increasing insulin resistance. In conclusion, a low-fat diet may preserve tissue HSP70 and health with aging, whereas high-fat diets, insulin resistance, and genetic factors may be more important than age for determining HSP70 levels." Which is good news for those folk who make an effort to maintain health and fitness into old age, as insulin resistance and weight gain are avoidable consequences of lifestyle for the vast majority of people.

Mice with the myostatin gene removed grow more muscle, and researchers have been looking into therapies for muscle wasting based on this mechanism for a number of years. Here is another confirmation that myostatin is involved in age-related changes in muscle mass and strength via its effect on stem cells:

"Human aging is accompanied by a progressive loss of muscle mass (sarcopenia). We tested the hypothesis that older males (OMs, 70±4 yr, n=9) would have a blunted myogenic response to a physiological stimulus compared to younger controls (21±3 yr, n=9). Subjects completed an acute bout of intense unilateral muscle loading. Young healthy males matched for body mass and activity level served as the control group. Muscle biopsies and blood were obtained before and at 3, 24, and 48 h after muscle loading.

The muscle stem cell response was analyzed. OMs had 35% fewer basal stem cells and a type II fiber-specific impairment in stem cell content and proliferation. Myogenic determination factor staining and cell cycle analysis illustrated a severely blunted progression through the myogenic program. Myostatin protein and mRNA were 2-fold higher in OMs. Stem cell-specific myostatin levels were not different at baseline; however, there were 67% more myostatin-positive type II-associated stem cells in OMs at 24 h. These data illustrate an age-related impairment of stem cell function in a fiber type-specific manner. The greater colocalization of myostatin with stem cells provides a mechanism for the impaired myogenic capacity of aged muscle."

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