Print this pagePrint this page

Will diabetes research lead to a cure for aging?


07.31.2010 23:46
The body’s aging process might seem, at first glance, to be unrelated to the disease we call ‘diabetes’. After all, the root causes of diabetes have to do with how the hormone ‘insulin’ is produced or used in the body, whereas the root causes of aging appear to be free radicals, malfunctioning genes, and damaged proteins.

Nevertheless, there is a connection between diabetes and aging — if not in their ultimate causes, then at least in the biochemical disruptions resulting from these causes, and in the symptoms that are produced by them. Because of these similarities, both diabetes and aging respond to some of the same treatments. This means that diabetes research is giving rise to anti-aging techniques, even though not a great deal of effort is going directly into anti-aging research itself. And it means that some of the supplements that are normally targeted at diabetic complications should also be used to fight aging in non-diabetics.

Let’s look briefly at what is known about the causes and symptoms of diabetes and of aging, and then at the treatments that they have in common.

Diabetes overview

There are two major types of diabetes: type 1 (‘juvenile onset diabetes’), and type 2 (‘adult onset diabetes’ or ‘non-insulin-dependent diabetes mellitus’). They are really two different diseases, although they share the property that sugar metabolism is impaired. Both type 1 and type 2 diabetes involve the hormone insulin, but in different ways.

Insulin is a hormone produced by the pancreas gland in response to rises in blood sugar levels; it tells the body’s cells to absorb and utilize glucose (the main blood sugar). Glucose, it so happens, is a two-faced substance: on the one hand, it is an important source of energy for cells; on the other hand, it is a destructive chemical — it damages the tissues that it comes into contact with. When glucose concentrations increase, the tissue damage happens faster.

Type 1 diabetes is caused by a genetic defect that allows the immune system to destroy insulin-producing cells in the pancreas. Without adequate insulin to tell cells to absorb and metabolize glucose, blood glucose can rise to very high levels after meals that contain sugar or other carbohydrates.

Type 2 diabetes appears to be caused by malfunctions in the molecular structures that carry signals from the outer walls of cells to the biological nano-machinery inside the cells — signals such as those sent by insulin. The details are not yet understood, but the result is that cells in muscles, liver, and other tissues are unable to utilize the glucose that they absorb, and so glucose accumulates in the body tissues and blood.

While type 1 and type 2 diabetes have different causes, both involve elevated glucose levels in blood and tissues. How do elevated glucose levels give rise to diabetic symptoms? Recent research suggests that the connection lies in the way cells produce energy from glucose. Under normal conditions, cells dissassemble glucose molecules, extract their internal energy and store it in the form of energy-rich molecules called ‘ATP’. Unfortunately cells perform this task sloppily and, as a side effect, produce destructive free radicals called ‘superoxide’. The body has an antioxidant enzyme, ‘superoxide dismutase’, that deactivates superoxide molecules before they can do much damage; but when glucose concentrations are too high, superoxide is produced faster than the dismutase enzyme can deal it. Superoxide molecules then escape in large numbers and wander around in cells doing more damage than usual. Among the structures that are damaged are the enzymes responsible for minimizing superoxide production, as well as the antioxidant enzymes themselves. This leads to even more superoxide production, which in turn promotes other destructive processes inside and outside of cells.

The direct and indirect harm that stems from high glucose levels and superoxide production includes:

Diabetic symptoms follow from these harmful effects, including:

Aging overview

Until recently the aging process was thought of as a proper and inevitable part of life. Today it is widely considered to be a disease or ailment — a process that can be treated and perhaps someday completely cured.

While aging is not well understood at the molecular level, it is partially understood. It appears to have at least five basic causes:

Three of the above causes of aging directly involve the genes — the DNA molecules that regulate the development and maintenance of body tissues. The fourth involves deposits of material that damage and kill cells either by their bulkiness or by harboring toxic substances.

The fifth cause of aging involves damage to the body’s large molecules, such as structural proteins, many of which are not routinely recycled and replaced by the body’s normal maintenance processes. This molecular damage has two known causes: the cross-linking of proteins by glucose or other biochemicals, and damage by free radicals. Let us examine these two damaging processes in more detail.

Free radicals and antioxidants

Free radicals are chemically reactive molecules (such as hydrogen peroxide) generated mainly as a side-effect of energy production in cells. Free radicals damage proteins, fats, and other molecules both inside and outside of cells. While some of the damaged molecules (such as fats and polysaccharides) are routinely replaced as part of the body’s normal maintenance routines, others are not. For example, structural proteins in connective tissue are not necessarily replaced at all. Molecular fibers such as collagen and elastin reside for years in the tissues, where they become increasingly damaged by cross-linkers and free radicals. This kind of damage is responsible for age-related tissue stiffness, loss of elasticity, and loss of the normal functions of the tissues.

Prevention of free-radical damage is the task of antioxidants. Antioxidant molecules sweep up free radicals and either neutralize them or carry them out of the body. The human body produces many of its own antioxidants (such as superoxide dismutase, alpha-lipoic acid, and glutathione peroxidase), and relies upon external sources for many others (such as vitamins C and E, and bioflavonoids).

The aging process, however, reduces the body’s ability to produce and utilize its own antioxidant enzymes — because the genes required to control the production of these enzymes become damaged, and the antioxidant enzymes themselves become damaged. It’s a ‘vicious circle’: free radicals damage the antioxidant enzymes and their genes, resulting in lower antioxidant production and the escape of more free radicals which further damage the genes and enzymes. Aging thus feeds on itself, eventually spiraling quickly into decrepitude unless preventive measures are taken.

Diabetes, like aging, also causes an increase in free radical production and a decrease in the body’s antioxidant defenses. The mechanisms are not fully understood, but the consequences are clear: damage to DNA, to structural proteins, and to the enzymes needed for metabolism and tissue maintenance.

Cross-linked proteins

Some chemicals, including sugars like glucose, are able to react chemically with certain amino acids in proteins, thereby bonding the proteins together. This cross-linking process is called ‘glycation’ if the cross-linker happens to be a sugar. Since the linked proteins have a restricted ability to move, cross-linking produces a stiff, inactive material called an ‘AGE’ (Advanced Glycation End-product). Drugs are being developed for preventing and even reversing this kind of damage in the body, and there are nutritional supplements that are thought to have similar actions.

As proteins get converted into AGEs by cross-linking, they lose their original functions. For example, elastin is a protein responsible for the elasticity of the skin and other tissues. Elastin molecules are nano-springs — when they are stretched, they try to pull back to their original length. But when extensively cross-linked, elastin fibers become fixed in length and can no longer be stretched. The skin loses its tension and it sags and wrinkles; tendons become stiff and easy to tear; blood vessels lose their flexibility and are prone to rupture.

Aging and diabetes: shared causes and symptoms

With regard to the mechanisms by which they damage the body, aging and diabetes have much in common. Both of them involve:

Diabetes and aging also have symptoms in common, including:

Let’s look now at some dietary supplements that are being studied as diabetic treatments and that also look promising as anti-aging supplements.

Anti-aging supplements from the diabetes arena

Many different dietary supplements have anti-diabetic properties. They fall into at least five categories:

Substances in all five of these categories have anti-aging properties, even when used by non-diabetics. Even the ‘insulin activity enhancers’ may benefit non-diabetics since evolution did not provide the human body with an insulin production apparatus capable of dealing with high blood sugar levels — such as those that occur, even in non-diabetics, after a sugary meal. Non-diabetics can therefore suffer glucose-induced tissue damage just as diabetics do, unless they take special measures to regulate insulin levels.

Antioxidants regarded as having value in treating diabetes include: alpha-lipoic acid, N-acetyl cysteine, ferulic acid, genistein, quercetin, vitamins C and E, coenzyme Q10, L-carnitine, manganese, zinc, glutathione, inositol, selenium, melatonin, and glucomannan. Most herbal supplements also have significant antioxidant properites and are used as diabetes remedies. Many of these antioxidants are quite familiar to anti-aging activists, but some are under-appreciated — ferulic acid, genistein, quercetin, and manganese, for example.

Insulin activity enhancers that may be of interest as aging inhibitors include: chromium picolinate, omega-3 fatty acids, genistein, conjugated linoleic acid, vanadium, vitamins C and E, magnesium, ginseng, Gymnema montanum, Aloe vera, bitter melon, onion, mistletoe extract, and olive leaf.

Glycation inhibitors: quercetin, rutin, L-arginine, and pyridoxamine.

Vascular function enhancers: benfotiamine and vinpocetine.

Nerve cell protectors: acetyl-L-carnitine, omega-3 fatty acids, quercetin, vitamin B12, inositol, and vinpocetine.

It is a fair guess that all of the above substances have some benefit as anti-aging supplements. To whittle the list down to a more convenient and affordable length one needs to consider not only the kind of action each substance has, but also where it exerts its effects in the body and in cells. The following shorter list is based on those considerations:

Conclusion

Is diabetes research leading to a cure for aging? A great deal of funding and scientific effort is going into the study of diabetes — a lot more than is going into anti-aging research — and we are fortunate that the two diseases have at least some elements in common: damage from free radicals, glucose cross-linking, and arterial plaques. Diabetes research is helping to provide techniques for preventing and reversing these causes of aging.

But what about the other causes of aging — damaged and inactivated genes, and faulty duplication of DNA? Are diabetes researchers developing techniques for dealing with these, also? At the moment, the answer is ‘no’ — genetic therapy is receiving very little attention. However, type 1 diabetes does involve defective genes, and type 2 diabetes involves damaged genes. It is therefore likely that these aspects of the disease will become important research topics. Considering the fact that diabetes research attracts huge amounts of money and expertise, it is reasonable to think that the study of this disease could indeed lead to a general cure for aging.