People commonly accept chronic disease as an inevitable part of aging. A high percentage of the elderly in industrialized nations routinely depend on medical care for disease management, often for survival. Thus, many body aches, pains, and age-related diseases are commonly attributed to the aging process. Many adults have come to accept the depressing prospect of eventual dependency on medical care.
Nevertheless, the underlying disruptions in biochemistry associated with chronic disease are distinctly different from the molecular changes solely due to aging. Although the prevalence of chronic disease increases with aging, this is a cumulative effect of pathology acquired over time, sometimes a life-time.
Many age-related diseases increasingly affect younger age groups. In fact, chronic disease in children is a growing problem. While aging provides more time for the development of chronic disease, aging is not a cause of any chronic disease apart from the impairments associated with aging itself. Rather than aging causing chronic disease, the facts support the concept that the inducers of disease can accelerate the aging process and reduce longevity.
Some facts and findings quoted from biomedical journal abstracts include the following:
Magnesium status may be compromised with ageing for two reasons: insufficient intake (magnesium deficiency) or alterations in magnesium metabolism (magnesium depletion). There is a large volume of literature suggesting that magnesium deficit contributes to the ageing process and to the vulnerability to age-related diseases. (Rayssiguier, Durlach, et al. 1993)
Available evidence suggests that the elderly need a mean serum concentration of >/=65 nmol/L of vitamin D to improve muscle performance and reduce the risk of falling and >/=75 nmol/L to reduce the risk of fracture. Many elderly persons in the United States and elsewhere have serum 25-hydroxyvitamin D concentrations below these levels. (Dawson-Hughes 2008)
We previously showed that the content of advanced glycation end products (AGEs) in the diet correlates with serum AGE levels, oxidant stress (OS), organ dysfunction, and lifespan. ... OS predisposes to the development of cardiovascular and chronic kidney diseases; calorie restriction (CR) is the most studied means to decrease OS, increase longevity, and reduce OS-related organ damage in mammals. ... the beneficial effects of a CR diet may be partly related to reduced oxidant intake, a principal determinant of oxidant status in aging mice, rather than decreased energy intake. (Cai, He, et al. 2008)
Neutrophil functions of the middle-aged group were worse than those of young adults and centenarians (lower chemotaxis and phagocytosis and higher adherence and superoxide anion levels). The neutrophil functions of the centenarians were closer to those of the young adults. ... With normal aging, total glutathione levels decrease, but the centenarians in this study showed levels similar to those of young adults. Centenarians showed the highest catalase activity of the three groups. (Alonso-Fernández, Puerto, et al. 2008)
Telomere shortening has been implicated in the aging process and various age-associated disorders, including renal disease. Moreover, oxidative stress has been identified as an initiator of accelerated telomere shortening. We have shown previously that maternal protein restriction during lactation leads to reduced renal telomere shortening, reduced albuminuria, and increased longevity in rats. (Tarry-Adkins, Joles, et al. 2007)
It is widely (although not universally) accepted that organismal aging is the result of two opposing forces: (i) processes that destabilize the organism and increase the probability of death, and (ii) longevity assurance mechanisms that prevent, repair, or contain damage. ... The expression of multiple detoxification enzymes, each with a significant but relatively modest effect on longevity, is coordinately regulated by signaling pathways such as insulin/insulin-like signaling, explaining the large effect of such pathways on life span. (Zimniak 2008)
Magnesium status may be compromised with ageing for two reasons: insufficient intake (magnesium deficiency) or alterations in magnesium metabolism (magnesium depletion). There is a large volume of literature suggesting that magnesium deficit contributes to the ageing process and to the vulnerability to age-related diseases. One of the biological changes associated with ageing is an increase in free radical formation with subsequent damage to cellular processes. Prime targets of the more reactive free radicals are unsaturated lipids in cell membranes, amino acids in proteins, and nucleotides in DNA. The accumulation of unrepaired oxidative damage products may be a major factor in cellular ageing. Magnesium-deficient animals show an increased susceptibility to an in vivo oxidative stress and their tissues are more susceptible to in vitro peroxidation. Moreover, the protective properties of various antioxidant drugs and nutrients suggest that free radicals are involved in the injury process of magnesium deficiency. The consequences on stress susceptibility, defective membrane functions and perturbation of intracellular calcium metabolism, inflammation, cardiovascular diseases including atherosclerosis and ischaemia/reoxygenation injury, diabetes, fibrosis, immune dysfunction and other diseases associated with ageing are presented and discussed.
Magnesium Research : Official Organ of the International Society for the Development of Research on Magnesium. 1993 Dec; 6(4):369-78.
Y. Rayssiguier, J. Durlach, E. Gueux, E. Rock, and A. Mazur
Centre de Recherche en Nutrition Humaine, Laboratoire des Maladies Métaboliques, INRA, St-Genès-Champanelle, France.
PubMed ID # 8155489
OBJECTIVES
To analyze several functions and antioxidant parameters of peripheral blood neutrophils from healthy centenarians (men and women) and compare them with those of healthy young (aged 25-35) and middle-aged (aged 65-75) men and women.
DESIGN
Cross-sectional study.
SETTING
Community-based.
PARTICIPANTS
Twenty-one healthy centenarians (8 men), 30 young adults (15 men), and 30 middle-aged adults (15 men).
MEASUREMENTS
Several neutrophil functions (adherence, chemotaxis, phagocytosis, and stimulated and nonstimulated intracellular superoxide anion levels) and antioxidant parameters (glutathione levels and catalase activity) were measured in peripheral blood neutrophil suspension in the three study groups.
RESULTS
Neutrophil functions of the middle-aged group were worse than those of young adults and centenarians (lower chemotaxis and phagocytosis and higher adherence and superoxide anion levels). The neutrophil functions of the centenarians were closer to those of the young adults. Age-related differences in neutrophil functions were fundamentally similar in men and women, except for intracellular superoxide anion levels, which were lower in young adult women than in young adult men. With normal aging, total glutathione levels decrease, but the centenarians in this study showed levels similar to those of young adults. Centenarians showed the highest catalase activity of the three groups.
CONCLUSION
Progressive impairment of the immune system accompanies aging. The better preservation of function and antioxidant systems in the neutrophils of centenarians could play a key role in the longevity of these subjects.
Journal of the American Geriatrics Society. 2008 Dec; 56(12):2244-51.
Patricia Alonso-Fernández, Marta Puerto, Ianire Maté, José Manuel Ribera, and Mónica de la Fuente
Geriatric Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain. palonsof@salud.madrid.org
PubMed ID # 19093924
We previously showed that the content of advanced glycation end products (AGEs) in the diet correlates with serum AGE levels, oxidant stress (OS), organ dysfunction, and lifespan. We now show that the addition of a chemically defined AGE (methyl-glyoxal-BSA) to low-AGE mouse chow increased serum levels of AGEs and OS, demonstrating that dietary AGEs are oxidants that can induce systemic OS. OS predisposes to the development of cardiovascular and chronic kidney diseases; calorie restriction (CR) is the most studied means to decrease OS, increase longevity, and reduce OS-related organ damage in mammals. Because reduction of food intake also decreases oxidant AGE s intake, we asked whether the beneficial effects of CR in mammals are related to the restriction of oxidants or energy. Pair-fed mice were provided either a CR diet or a high-AGE CR diet in which AGEs were elevated by brief heat treatment (CR-high). Old CR-high mice developed high levels of 8-isoprostanes, AGEs, RAGE, and p66(shc), coupled with low AGER1 and GSH/GSSG levels, insulin resistance, marked myocardial and renal fibrosis, and shortened lifespan. In contrast, old CR mice had low OS, p66(shc), RAGE, and AGE levels, but high AGER1 levels, coupled with longer lifespan. Therefore, the beneficial effects of a CR diet may be partly related to reduced oxidant intake, a principal determinant of oxidant status in aging mice, rather than decreased energy intake.
The American Journal of Pathology. 2008 Aug; 173(2):327-36.
Weijing Cai, John C. He, Li Zhu, Xue Chen, Feng Zheng, Gary E. Striker, and Helen Vlassara
Department of Geriatrics,Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA.
PubMed ID # 18599606
Telomere shortening has been implicated in the aging process and various age-associated disorders, including renal disease. Moreover, oxidative stress has been identified as an initiator of accelerated telomere shortening. We have shown previously that maternal protein restriction during lactation leads to reduced renal telomere shortening, reduced albuminuria, and increased longevity in rats. Here we address the hypothesis that maternal protein restriction during lactation is nephroprotective and associated with increased expression of antioxidative enzymes and decreased age-dependent renal telomere shortening. Newborn rats were suckled by a dam fed either a control (20% protein) or low-protein (8% protein) diet. All animals were weaned onto standard chow. Offspring that had been suckled by protein-restricted mothers had reduced albuminuria, N-acetyl-glucosaminidase, and urinary aldosterone excretion. These animals also did not show significant age-dependent renal telomere shortening and hence had significantly longer telomeres at 12 mo of age. This lack of renal telomere shortening was associated with increased levels of the antioxidant enzymes manganese superoxide dismutase, glutathione peroxidase, and glutathione reductase. These findings suggest that beneficial effects of slow growth during lactation are associated with increased antioxidant capacity and prevention of age-dependent telomere shortening in the kidney.
American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2007 Sep; 293(3):R1259-66.
Jane L. Tarry-Adkins, Jaap A. Joles, Jian-Hua Chen, Malgorzata S. Martin-Gronert, Dionne M. van der Giezen, Roel Goldschmeding, C. Nicholas Hales, and Susan E. Ozanne
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, UK. jane.adkins@ntlworld.com
PubMed ID # 17581837
Telomere shortening has been implicated in the aging process and various age-associated disorders, including renal disease. Moreover, oxidative stress has been identified as an initiator of accelerated telomere shortening. We have shown previously that maternal protein restriction during lactation leads to reduced renal telomere shortening, reduced albuminuria, and increased longevity in rats. Here we address the hypothesis that maternal protein restriction during lactation is nephroprotective and associated with increased expression of antioxidative enzymes and decreased age-dependent renal telomere shortening. Newborn rats were suckled by a dam fed either a control (20% protein) or low-protein (8% protein) diet. All animals were weaned onto standard chow. Offspring that had been suckled by protein-restricted mothers had reduced albuminuria, N-acetyl-glucosaminidase, and urinary aldosterone excretion. These animals also did not show significant age-dependent renal telomere shortening and hence had significantly longer telomeres at 12 mo of age. This lack of renal telomere shortening was associated with increased levels of the antioxidant enzymes manganese superoxide dismutase, glutathione peroxidase, and glutathione reductase. These findings suggest that beneficial effects of slow growth during lactation are associated with increased antioxidant capacity and prevention of age-dependent telomere shortening in the kidney.
American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2007 Sep; 293(3):R1259-66.
Jane L. Tarry-Adkins, Jaap A. Joles, Jian-Hua Chen, Malgorzata S. Martin-Gronert, Dionne M. van der Giezen, Roel Goldschmeding, C. Nicholas Hales, and Susan E. Ozanne
Department of Clinical Biochemistry, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, UK. jane.adkins@ntlworld.com
PubMed ID # 17581837
The objective of this article was to consider key evidence that treatment of vitamin D insufficiency has measurable clinical benefits for the musculoskeletal system in the elderly. The functional outcomes considered were increased bone mass, decreased rates of bone loss, improved muscle performance, reduced risk of falls, and reduced fracture incidence. Available evidence suggests that the elderly need a mean serum concentration of >/=65 nmol/L of vitamin D to improve muscle performance and reduce the risk of falling and >/=75 nmol/L to reduce the risk of fracture. Many elderly persons in the United States and elsewhere have serum 25-hydroxyvitamin D concentrations below these levels. For this reason, supplementation is likely to provide significant benefit to this segment of the population.
The American Journal of Clinical Nutrition. 2008 Aug; 88(2):537S-540S.
Bess Dawson-Hughes
Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. bess.dawson-hughes@tufts.edu
PubMed ID # 18689397