What distinguishes "Biology of Aging and Age-related Diseases" project at MedILS from other research projects on aging and diseases is the commitment to find the root cause of aging and age-related diseases rather than bet on some of countless consequences of aging. Age-related diseases are the consequences of aging that are of prime interest to us since they account for 90% mortality in European countries. Since everybody is subject to aging, aging cannot be a disease, but it is a condition that causes all age-related diseases such as malignant, degenerative (e.g., cardio-vascular and neurodegenerative diseases), as well as infectious, parasitic and many autoimmune diseases (e.g., rheumatoid arthritis) caused by the age-related weakening of the immune system.
Epidemiology suggests that aging and all age-related diseases that, like death, increase roughly with 5th power of time lived, might have a common cause. MedILS' scientists have established that the most likely common cause of aging and age-related diseases is oxidative damage to the constituents of the proteome, known (since the pioneering studies of Earl Stadtman) to increase exponentially with age. Further, our results suggest that the predisposition to a specific age-related disease can be subject to diagnosis, even predictably, by the identification of mutational polymorphisms that sensitize a given protein to oxidative damage.
This concept (i) predicts the reversibility of aging and diseases that was recently demonstrated in heterochronic parabiosis experiments with mice and (ii) offers strategies for prevention, attenuation and cure of degenerative diseases by acting upon their cause.
Another concept called cellular parabiosis is useful to understand the basis of long latency period (a couple of decades) in the emergence of degenerative and malignant age-related diseases. Cellular prabiosis can suppress the manifestation (phenotype) of initiated disease, and even reverse the manifested disease, by the molecular traffic of molecules and organelles between neighboring cells. Chronic inflammation destroys cell-cell communication and leads to activation of dormant disease. Hence, appropriate anti-inflammatory treatments may keep the diseases in a chronically dormant state.
Projected applications to health and longevity.
First area of application is of diagnostic kind. It is based on (i) quantitative estimates of the degree of global proteomic oxidative damage that correlates (probably causally) with the biological age of a person and (ii) identification of (a) particular protein(s) that is (are) more oxidatively damaged in the tested person than in general population of the same age - a kind of identification of weakest link that will manifest itself with age as a particular pathology.
Second area of application is mitigation of diseases - exceptionally, of both preventative and curative kind, by the same treatment. Our concept relies upon identification of the cause of age-related diseases and of predisposition to diseases leading to two approaches that could act each to both prevent, attenuate and cure such diseases and hence prolong health span.
One approach is "generic" using a balanced mixture of effective antioxidants, such as those present in robust organisms (Deinococcus, Arthrobacter, Bdelloid rotifers and robust plants like the rose of Jerrico), which could keep the level of oxidative proteome damage as low as in young age.
Another preventative-therapeutic approach is specific by targeting the (selected or synthesized by design) protective molecule (an antioxidant chaperone) to the disease-relevant protein that is sensitized to damage by a polymorphism, i.e., mutation.
First therapeutic approach is targeted to preventing both aging and diseases. The second one should specifically protect against the emergence of genetically predisposed diseases as well as cure the disease by eliminating most, or all, of its consequences due to a generally rapid protein turnover. A third approach - cellular parabiosis - can keep diseases in a dormant/latent state or even reverse disease by anti-inflammatory
A critical comment: The dichotomy between successful cure of infectious disease by antibiotics and unsuccessful therapies of degenerative diseases can be readily understood. Antibiotics target the known cause of infectious disease (a microbe) and therefore can cure it in a short time. Hence, "targeting drugs" became a fashionable pharmaceutical approach. However, since the root cause of age-related diseases is unknown, it cannot be targeted effectively. Short of relevant knowledge, new "smart drugs" were made to target some particular, but arbitrary (by the chance of experimental observation) molecular consequence, usually a secondary effect, of the disease. Targeting such chance-selected downstream steps or consequences of disease is not expected to provide cure, and it does not. Such drugs do not serve patients and public health but business by impoverishing both patients and public health funds.
We believe that, by improving the quality of cellular proteomes, biological rejuvenation is the most secure way to mitigate age-related diseases because they are always caused by the malfunction of proteins.
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Cellular parabiosis and the latency of age-related diseases
Protein damage, ageing and age-related diseases