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.
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:
- formation of cross-links between proteins in the tissues;
- energy starvation by cells that cannot properly utilize the available glucose;
- inadequate production of needed biological substances, such as antioxidants, enzymes, and growth factors;
- increased production of free radicals;
- damage to DNA, inactivation of needed genes;
- impaired physiological processes, such as the growth and maintenance of body tissues.
Diabetic symptoms follow from these harmful effects, including:
- stiffening and loss of function of tissues, due to cross-linked proteins and free radical damage;
- damage to nerves, eyes, skin, kidneys, immune system, and all other organs;
- cardiovascular ailments, including atherosclerosis, heart attack, stroke, poor circulation;
- impaired wound-healing;
- susceptibility to infection, due to impaired immune system;
- an acceleration of the apparent aging of the whole body.
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 â€” 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:
- damaged genes (i.e., damage to DNA caused by high-energy particles such as UV light and x-rays, viruses, free radicals, sugar aldehydes, or other chemicals in the body);
- inappropriate activation or deactivation of genes;
- faulty duplication of the genetic material, DNA, during cell division;
- accumulation of bulky molecular debris, such as amyloid protein and lipofuscin;
- damaged structural molecules, especially proteins, inside and between the cells of body tissues.
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 â€” 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.
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:
- increased free radical activity due to loss of antioxidants;
- damage to structural proteins caused by cross-linking;
- damage to genes by free radicals and by sugar aldehydes;
- accumulation of bulky molecular debris, including amyloid and lipofuscin.
Diabetes and aging also have symptoms in common, including:
- Loss of elasticity and flexibility of skin and other tissues;
- Skin ailments – such as infections, discolored spots, thin skin, rashes;
- Cardiovascular disorders – poor circulation, atheroscerosis, blood clots, strokes, heart attacks;
- Increased cancer prevalence;
- Eye disorders – cataracts, glaucoma, retinal degeneration;
- Hearing loss;
- Cognitive impairment, memory loss, dementia;
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:
- Antioxidants – to counteract free radical damage to body tissues;
- Insulin activity enhancers – to increase the production of insulin or of insulin receptors;
- Glycation inhibitors – to prevent the cross-linking of proteins by sugars;
- Vascular function enhancers – to improve blood circulation;
- Nerve cell protectors – to prevent or repair damage to nerve cells.
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:
- Pyridoxamine inhibiting diabetes-related damage to the body
- benfotiamine protects blood vessels from damage by glucose.
- Resveratrol antioxidant and also has direct effects on the activities of certain genes and proteins.
- vitamin B12 improves nerve function; deficiencies are common.
- alpha-lipoic acid antioxidant; acts in mitochondria (where superoxide is produced); acts in solution and in membranes.
- vitamins C and E antioxidants that act in solution and membranes.
- selenium antioxidant; needed for making glutathione peroxidase.
- N-acetyl cysteine (NAC) precursor for the antioxidant glutathione, an essential cofactor of glutathione peroxidase.
- manganese antioxidant; needed for making superoxide dismutase.
- ferulic acid antioxidant; acts against superoxide; enhances other antioxidants; suppresses blood glucose; improves cholesterol profile; may prevent UV damage to skin.
- genistein antioxidant; insulin activity enhancer; protects brain cells; inhibits LDL oxidation (a cause of atherosclerosis).
- quercetin glycation inhibitor; glucose and sorbitol suppressor; acts in membranes.
- vinpocetine improves circulation, especially in the brain and retina.
- acetyl-L-carnitine improves nerve function; increases efficiency of glucose and fat metabolism; acts in mitochondria.
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.