Rather than a discussion of demographic and psychographic data related to aging, we have chosen to review key physiological factors associated with the aging process. Sandy Bigelow, PhD, principal with Vanguard Global Associates, is an expert in this area. Following is Dr. Bigelow’s summary of the well studied physiological and biochemical processes commonly associated with aging.
Science of the Aging Process
Aging is a normal biological process that, in and of itself, is not a disease process. However, after 35 years of age, the onset of physiological and cellular senescence is characterized by a declining ability to respond to stress, increasing homeostatic imbalance and increased risk of disease. The major clinical endpoints and biological systems that change and control progression of the aging process are mitochondrial changes/toxicity, changes in telomere length (affected by changes in sirtuin-mediated responses), the accumulation of glycated proteins and TOR1 and TOR2 gene variants.
Sirtuin-Mediated Responses. Sirtuins are a set of seven genes associated with aging processes including muscle aging, sarcopenia (loss of skeletal muscle mass), age-related cardiac dysfunction and lower serum levels of insulin-like growth factor (IGF). Sirtuins play an essential role in the cellular response to environmental stress, promoting DNA repair.
For instance, sirtuins alter and repair chromatin (the scaffolding proteins that support DNA structure, repair and integrity). Sirtuins are enzymes that de-acetylate histones (i.e., the proteins that constitute chromatin), and facilitate DNA and telomere stability and repair. SIRT1, a sirtuin enzyme, is a key regulator of oxidative metabolism and its activity is regulated by nutritional status, being up-regulated throughout the body by fasting and calorie restriction, and activated by select polyphenols. Natural products that induce sirtuin activity include resveratrol, which is naturally found in grapes. Studies suggest lifetime feeding of resveratrol to rodents extends their lifespan by about 20%.
Telomere Length. Human cells in culture divide a finite number of times (about 20) before death. It has been found that the number of divisions human cells undergo depends on the length of telomeres. Telomeres reside at the end of every chromosome (condensed pieces of human DNA), consist of repeated DNA sequences and get chopped off with each cell division event. The longer the telomere, the longer the life of the cell. When telomeres are shortened, cellular senescence emerges, and when telomeres are gone, the human cell dies. As cells progress through senescence and toward death our organs start to fail. The enzyme, telomerase, is responsible for maintaining telomere length. High serum levels of vitamin D and omega-3 fatty acids are associated with telomere maintenance.
DNA Damage & Repair. Human DNA is damaged on a continuous basis. Luckily, the DNA repair system works fastidiously to repair virtually all DNA damage on a continuous basis. Evidence shows that the ability of the DNA repair process to correct all DNA damage diminishes over time as humans mature. Uncorrected DNA repair (and chromatin repair) is strongly associated with the onset and progression of age-related damage, including cancer and neurological diseases such as Alzheimer’s. DNA repair depends in part on DNA methylation, a normal process often associated with cognition. Natural dietary substances that inhibit DNA damage include carnosine, as well as withanone from Ashwagandha.
Mitochondrial Toxicity & Degradation. Mitochondria are cellular organelles responsible for driving energy metabolism, known commonly as the cell’s power plant, which convert energy from nutrients into ATP (the biochemical form of energy). Natural products such as resveratrol activate mitochondrial biogenesis and oxidative capacity; substances sourced from ginseng, ginkgo, nuts, grains, tomato and soy that include phytoestrogens, curcumin, melatonin, polyphenols, antioxidant vitamins (A, C and E), carnitine, carnosine and ubiquinone are found to ameliorate or even abrogate mitochondrial damage. Withanone, a major alkaloid from Ashwagandha has been found to reduce reactive oxygen species (ROS), DNA and mitochondrial damage, as well as induce cell defense mechanisms.
AGE Proteins, Unfolded Protein Response & Protein Plaque Formation. The endoplasmic reticulum (ER), an organelle located inside the cell, consists of a network of tubules extending from the nucleus to the outer cell membrane. The ER is responsible for the synthesis of proteins (e.g., enzymes and structural proteins) and the ubiquitous secretory activities of the cell, involving processes for proper protein folding and maturation (modification with sugars, etc.).
If cell damage resulting from improper protein folding and modification is adequately severe, the UPR process leads to cell death. AGE proteins and UPR initiation is associated with the loss of bone mass, metabolic syndrome and liver malfunction. Pentosidine levels are also associated with greater cognitive decline.
Natural dietary substances that reduce the production of AGE proteins or the initiation of the UPR process include amino acids, arginine, beta-hydroxy-beta-methylbutyrate (HMB), leucine and a variety of fruit and vegetable seed extracts.
Mammalian Target of Rapamycin (mTOR). The mTOR is a biochemical pathway that regulates cell longevity by acting as the master regulator of protein translation and telomerase, and is able to induce cellular senescence. mTOR has been linked to aging through the insulin signaling pathway by inhibiting insulin growth factor-1. Autophagy is a process by which the body recycles old or damaged cell parts and keeps the healthy cells and the body running efficiently. Restricted calorie diet reduces mTOR activity allowing for autophagy to rid unhealthy cells (like pruning a tree). Autophagy recycles damaged or old parts of cells while damage from reactive oxygen species is reduced to make cells function better. Examples of natural dietary substances that activate mTOR are leucine and resveratrol.
Neuronal Longevity. After 20 years of age, there is a 10% decrease in the number of neurons (nerve cells) for every decade of life. Neuronal cell death can be caused by the accumulation of AGE proteins resulting from altered protein homeostasis. In addition, autophagy leads to a release of ROS, reactive nitrogen species (RNS) and free radicals, and the initiation of peroxidation reactions by peroxisomes. ROS, RNS and free radicals will induce premature cell death, which can be a factor in the underlying etiology for dementia. Natural dietary substances that reduce the production of AGE proteins or the initiation of the UPR process inside neurons include arginine, citrulline and DHA, as well as those that provide antioxidant properties, including Ginkgo biloba extract.
The market for Baby Boomers has already emerged and is expanding rapidly as they experiment with multiple modalities and interventions to mitigate and forestall the health effects of aging. Dietary interventions, including those mentioned here, can contribute to a healthy diet to mitigate Father Time.
References available upon request.
Gregory Stephens, RD
Greg Stephens, RD, is president of Windrose Partners, which serves clients in the the dietary supplement, functional food and natural product industries. Formerly vice president of strategic consulting with The Natural Marketing Institute (NMI) and vice president of sales and marketing for Nurture, Inc (OatVantage), he has 25 years of specialized expertise in the nutritional and pharmaceutical industries. He can be reached at 215-860-5186; E-mail: email@example.com.
Sandy Bigelow, PhD
Vanguard Global Associates LLC
Sandy Bigelow, PhD, principal, Vanguard Global Associates LLC, is a research and development professional with more than 20 years of experience in leading global technology responsibilities in the food, nutrition and medical device industries. He can be reached at firstname.lastname@example.org.