Growing, developing and aging (GDA) are characteristic of all living organisms and have a multifactorial etiology. Three major intrinsic categories influence growth, development and aging in humans. These include genetics, hormones (endocrine system) and paracrine. An extrinsic influence is the environment. These categories all interact with each other to determine roles of individual factors. Growth and development patterns are flexible (plastic) to a point depending on when and how significant the environmental perturbation.
During growth, when certain environmental factors are compromised, the body slows its growth and can catch up to its genetic programming providing the perturbations are not too intensive or prolonged. Diseases that involve high temperatures are the most stressful for causing growth disruption. Some tissues and systems are more readily thrown off their developmental pathway. The hypothesis that the body can get thrown off its programmed genetic growth by numerous interacting factors is called the concept of heritability. Knowledge of tissue growth is important primary information to understand what happens to us when we age.
If we come to an understanding of growth, development and aging, including the processes involved, we will be able to identify early deviations that may precede disease in later life. There is an association between a low weight at birth, rapid postnatal growth and childhood and adult obesity and glucose tolerance. The rebound adiposity timing during adolescence can also be a precursor to the development of obesity at a later life stage. Cameron and Demorath identify fetal life, infancy, childhood, and adolescence as the critical growth periods. Each of these stages involves different aspects of human growth and development.
Environmental affects during these stages are necessary in order to allow for proper growth but can also have a deleterious effect on growth and development which can influence Complex Chronic Diseases (CCD). These key phases have been examined in many publications. According to Noel Cameron and Ellen W. Demerath, a developing fetus uses a process called “programming” in order to counter insults during the pre-natal period that may effectively deal with the immediate issue but that may result in long term disadvantages such as cardiovascular disease, (hereafter referred to as CVD), hypertension, Type II diabetes and the development of obesity later in life.
One way in order to test for a pre-natal insult is through enamel hypoplasia. During enamel development, if there is a major insult, the calcification of the enamel is affected leaving a permanent line on the tooth called enamel hypoplasia. Because dental developmental is under fairly rigid genetic control, the timing of the insult can be determined by noting the position of the line(s) on the crown. There is much debate on whether after early childhood if adipose is post-mitotic; weight increase after childhood is a function of hypertrophic mechanisms.
During the fetal stage of development, the brain grows multiplicatively up to the 6th prenatal month then has exponential auxetic growth in infancy. The skeleton has exponential growth in prenatal and into childhood at which point it follows a general growth curve until adolescence. Muscle, like the brain, is post-mitotic but multiplicative growth last to birth then it is auxetic. Adipose tissue is abundant at birth and constitutes 25% of babies’ weight. Babies lose the adipose tissue during childhood but it increases at adolescence, particularly in females where the menses will be delayed if there is not a threshold amount of adipose tissue.
There is controversy over whether fetal environmental stressors are independent from genetic factors. Certain populations are more prone to obesity than others such as Amerindians which has led to the “Thrifty Gene Hypothesis. ” The concept is that there are pleiotropic effects of specific genetic variants that take place in fetal development and in “cardiovascular, metabolic and hormonal regulation later in life” (2002:178). Certain groups of North American aboriginals have a high predilection to developing Type II diabetes. Infectious diseases are known to inhibit growth.
The exact mechanisms are not known but definitely, those diseases that have fevers (febrile) disrupt growth. The fever disrupts normal cell division (reduced mitotic index). This slows chondrogenesis but does not seem to influence osteogenesis resulting in growth arrest lines on long bones. Infectious disease may reduce growth hormone because of an increase in corticosteroids from the adrenal cortex. During illness, malnutrition acts synergistically with disease to disrupt growth. Studies have shown an association between birth weight and the risk of diabetes and glucose intolerance.
The proximate mechanism behind the relationship between birth size and disease risk is that the fetus adapts to maternal under-nutrition by growth retardation which leaves the adult better equipped to cope in a deprived rather than an enriched postnatal environment. The key is the plasticity during the course of post-natal development. This is not necessarily low birth weight alone which may have resulted from energies being routed to the growth and development of the brain to the detriment of the development of other tissues. This environmental impoverishment is believed to result in permanently modified fetal physiology and programming.
The proposition is that once there is a modification in fetal programming, organ systems are then unable to act in response to a “high-calorie, high-fat, and high-sodium diets leading to a higher incidence of adult disease” (2002:163). Catch-up growth after an insult can result in changes to the timing of peak growth in certain organs. The hypothesis is that such things as the number of kidney cells at birth, (nephrons), is due to nutritional deficiencies during pre-natal life that will affect risk of hypertension in later life.
Results from some studies have proposed that malnutrition may retard the growth and development of the hypothalamus in such a way that appetite control and energy maintenance are compromised. Infants that are large at birth, studies have revealed, have an increased risk of obesity in childhood. New associations have shown that small-for-gestational-age individuals are born with enhanced insulin sensitivity and the insulin resistance appears in later life which translates into a predisposition for diabetes. Childhood obesity tends to lead to a higher incidence of obesity during puberty.
If the adiposity rebound has taken place before the age of 6, “obesity may be entrained during development” (2002:169). Children with this early adiposity rebound tend to have an advanced maturation of the skeleton that can also influence an earlier maturation of puberty which brings an increased risk of adult obesity. There is a lack of a clear correlation however as other factors such as parental and earlier obesity cannot be excluded from the analysis and are themselves risk factors for obesity. An increased rate of growth in childhood also means that there is an increased rate of cell turnover which can in turn lead to the risk of the duplication of malignant cells.
Rapid growth is enabled by the protein IGF-1 which encourages cell division and impedes apoptosis. Rapid growth also hastens reproductive development. The antecedents of this early onset of puberty, which include rapid growth and obesity, increase the risk of CVD and diabetes. Obese children and those with high weight/height ratios reach pubescent maturity much earlier according to Cameron and Demerath’s studies. Puberty results in many changes within the body. These can include such things as an increase in fat in female bodies (with a corresponding increase in leptin concentrations), and a decrease in fat in male bodies (with a corresponding decrease in leptin concentrations).
In epidemiology, it is imperative that there is an understanding of the difference between association and cause. It is difficult to isolate leptin as a “master regulatory hormone, orchestrating both the hormones of growth and maturation and weight-regulating mechanisms” (2002:173) and more research is needed in this area according to Cameron and Demerath. Older adults in western societies have numerous complex chronic diseases that include obesity, cardiovascular disease and diabetes that are concomitant of risks of lifestyle as well as their fetal and perinatal environments known as the (DOHaD) paradigm shift.
The developmental origins of health and disease paradigm (DOHaD) is a multi-disciplinary field that studies the way in which “environmental factors acting during the phase of developmental plasticity interact with genotypic variation to change the capacity of the organism to cope with is environment in later life” (2006:1). Life History Theory (LHT) is a branch of evolutionary theory that attempts to account for ways in which the stages of the life cycle and the behaviours associated with them are organized and is the cornerstone of evolutionary medicine.
The main concern today is the increasing potential for development of Complex Chronic Diseases such as cardiovascular disease and diabetes. CCD usually has multifactorial causes that broadly involve genetics, infectious and non-infectious environmental agents and to look for a single cause is illogical. The molecular clock of aging are made up of a repeating series of six nucleotides (bases). A typical human telomere may have more than 1500 repeats. As progressive cell divisions occur, the overall chromosomal length gets shorter. A cell’s age can be determined by examining telomere length.
This reduction of telomere length impacts “degenerative processes of aging through its impact on cellular senescence” (2002:159). When the chromosome reaches a certain length, it self-destructs. Early growth deviation is generally reputed to have a causal link to Complex Chronic Diseases, (CCD). Key environmental factors are the synergistic actions of nutrition and disease. Some nutritional conditions can result in changes in the hormonal environment. Cameron and Demerath conclude that additional research is required in this area in order to illuminate “the evolution of senescence in the human species” (2002:178).
Cameron and Demerath recognize that whether the deviation of growth specifically “programs” health in later years or whether it is only an indicator for the deviations is not known and also would benefit from future studies. References Cameron, Noel, and Ellen W. Demerath. 2002. Critical periods in human growth and their relationship to diseases of aging. American Journal of Physical Anthropology 119 (S35): 159-84. Gluckman, Peter and Mark Hanson, eds. 2006 The developmental origins of health and disease: and Overview, in Developmental Origins of Health and Disease. Peter Gluckman and Mark Hanson, eds. Pp. 1-5. Cambridge: Cambridge University Press.