BIOGERNOTOLOGY-1

R.A.S HEMAT, MB;BCh, FRCSI, DUL.

Biogernotology describes age-related changes in cells, tissues and organisms. It is highly complex implicates both genetic and epigenetic stochastic causative factors. There are no any apparent deterministic, predictive or universal biomarkers of ageing.

The hallmark of cellular aging is the failure of senescent cells to initiate the DNA synthesis during the progression of cell cycle. One of the common features of cells from senescent tissues is the accumulation of abnormal proteins. Aging is associated with a progressive reduction in almost all physiological functions. At the cellular level, aging results in the inability of cells to proliferate. Senescent cell remains metabolically active for long periods of time, but there are progressive changes in cell structure and function. Several proteolytic systems participate in intracellular protein degradation. Calpains partially degrade membrane and cytoskeletal proteins and several membrane-associated enzymes. A diminution of thiols in senescent cells, as a consequence of free radical reactions and oxidative damage, may cause enhanced calpain translocation to the cell membrane.

During senescence, there are severe changes in the autophagosome/lysosomal system. The CNS is one of the tissues that show the most dramatic changes in protein degradation with age.
During aging there is a progressive loss of muscle mass that originates because of an imbalance between synthesis and degradation of proteins. No changes in levels of ubiquitin conjugating enzymes in lenses were detected with age, but changes in their ability to respond to oxidative stress were found.

The age-related changes in calcium signal mobilisation may result from alterations in production of IP3. There is selective alteration in PKC isoenzymes in T cells during aging, which might contribute to alterations in intracellular signalling events.
Aging results in a significant decline in immune function that has been directly or indirectly linked to increased susceptibility to infections, autoimmunity, and cancer. Serum concentrations of IgG and IgA increase, whereas the concentration of IgM is either unchanged or decreases with age. NFkB can be activated by a wide variety of physiological and non-physiological stimuli including cytokines, mitogens, viruses and viral products, oxidative stress, and chemical agents such as phosphatase inhibitors and ceramide. Aging may affect post translational processes required for activation of transcription factors rather than affecting constitutive levels.

Immunosenescence may contribute to decreased pathology in elderly individuals, as in the lesser degree of acute rejection seen in clinical corneal and kidney transplantation.
Haematopoiesis may be compromised because of a severely reduced capacity to produce GM-CSF and because lower numbers of progenitor cells are present in the BM. Lower levels of thyroid hormones and insulin may be responsible for lower thymulin levels.
Damage to the cytoskeleton paralleling aging may have profound effects on cell function.
Telomere length in sperm DNA does not decrease with increasing age, suggesting that a mechanism for maintaining telomere length may be active in germ cells but not somatic cells, i.e. telomerase.

Vaccination may have a less long-lasting effect in elderly. Responses to secondary antigens may normalise after boosting in elderly, but the improved response is not sustained for the same duration as in the young. The prime cause of death is infectious disease in the elderly over 80’s (i.e. pneumonia, influenza, gastroenteritis, bronchitis). Not only vitamin but also trace element-deficiencies in the elderly may contribute to immunodeficiency. Whereas levels of cortisol increase with age in both men and women, in general the levels of DHEA decline with age.

The NMDA receptors are present at high density in the cerebral cortex and hippocampus. The NMDA receptors appear to be more vulnerable to the aging process than other glutamate receptors and show declines in their binding densities, electrophysiological functions, and influence on other transmitter systems. The age-associated changes in the NMDA binding site are not homogeneous across brain regions.

The pathobiology of osteoporosis resulting from sex-steroid deficiency or glucocorticoid excess involves increased osteoblast apoptosis. Fractures are a direct manifestation of bone fragility and are therefore a key component of an osteoporosis phenotype. It is important to treat vitamin D deficiency to prevent wintertime bone loss and a possible increase in fracture risk. Bone loss from chronic acidosis may be prevented by increasing dietary base intake. A small drop in pH causes a tremendous burst in bone resorption. . Animal proteins and cereals are rich sources of phosphoric and sulphuric acid, which are recognised as acid ash foods. Humans become more acidic as they age; the more acid precursors consumed, the greater the degree of systemic acidity. Protein undernutrition, with normal calorie intake, reduced IGF-1 levels independently of growth hormone secretion. Lower protein intake is significantly associated with greater bone loss at the spine and femur skeletal sites.

Reduced muscle strength in the elderly is a major cause of disability and may also account for the high prevalence of falls. The recommended daily allowance (RDA) for protein of 0.8 g/kg body weight per day may be inadequate to meet the needs of elderly people. Aging is associated with decreased thirst, even when dehydrated. More food or even a nutritional supplement may not result in body weight gain in elderly people.

The physiologic anorexia of aging may involve alterations in both the peripheral satiation system and the central feeding drive. Alterations in body mass index occur over the life span, with the greatest mass (and obesity rates) occurring during the middle decades (40-60 y) with a decline thereafter. There are clear declines in olfaction and less obvious alterations in taste sensation with aging. With aging, there is a decline in gastric emptying of large meals that has been associated with satiation. In humans amylin levels increase from middle age to old age suggesting a possible role for amylin in the anorexia of aging. Declining nitric oxide may play both a peripheral and central role in the pathogenesis of the anorexia of aging.

Damage to human skin due to ultraviolet light from the sun (photoaging) and damage occurring as a consequence of the passage of time (chronologic or natural aging) are considered to be distinct entities.

Decrease in DHEA and DHEAS is a constant feature of advancing age. By the 5th decade of life DHEA levels decrease (<30%). The declining levels of DHEA parallel a decrease in well-being. Parental androgen does not provide normal circadian patterns of serum testosterone and the injection is uncomfortable. Serum sex hormones have no relation to the development of CaP. There is no effect of exogenous androgens on PSA or prostate volume. There is no credible evidence that prostatic biopsies are indicated before initiation of androgen supplementation.

March, 2002

Note: The information in this article has been excerpted from the following books: urotext-ebook simplifying urology, Principles of modern urology, Principles of Orthomolecularism, Andropathy, by Dr. R.A.S HEMAT. Permission is granted to copy and redistribute this document electronically as long as it is unmodified. This article may not be sold in any medium, including electronic, CD-ROM, or database, or published in print, without the explicit, written permission of Dr. R. A. S. Hemat.

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Dr. R.A.S HEMAT declares no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, stock holdings, gifts, or honoraria.