Today most people in the world can expect to live as long as those in the very richest countries in 1950. We are living longer than ever. But can we live better?
As a population, we are living longer than we ever have before, but this is often accompanied by the consequence of spending an extended period of time feeling sick. For many people, getting old means spending more time in pain. Aging is an inevitable part of life. As we grow older, we start to experience changes in our physical and mental health that can be concerning. Health is one of the most important things that we possess but is often taken for granted until it becomes a problem that complicates our daily lives. Our current understanding of the aging process is limited. Still, constant growth and development in this field are very promising and could give us the power to maintain or improve our quality of life into old age.
Aging feels different to everybody, but there are some significant aspects commonly experienced by all at some point in their lives. Some of the first physical signs people experience are growing aches and pains in their joints and muscles, most commonly experienced as a steady increase in chronic pain with age. This can largely be attributed to an overall increase in inflammatory factors in our blood with age, often referred to as “inflammaging” (1). While this increase in inflammation is often associated with conditions like arthritis and skeletal aging, it can also contribute to various other conditions such as Diabetes, Alzheimer’s disease, Atherosclerosis, Irritable Bowel Syndrome (IBS), Cancer, and many more. Additionally, a major decline in COVID-19 outcomes with age is attributable primarily to an overactive inflammatory response to infection (2). When a young person is infected with a pathogen, they recover quickly, dispose of damaged cells, and restore tissues that have been damaged. An older person exposed to the same pathogen is much more likely to accumulate aging immune cells, leading to chronic inflammation.
A widespread characteristic of aging is an overall lowered energy state, making it harder to complete everyday tasks. A variety of mechanisms contribute to this phenomenon but a key component is the loss of our body’s ability to properly sense nutrients. With age, our insulin and insulin-growth factor-1 pathway has a reduced ability to sense nutrients, specifically glucose. Further, another famous protein involved in building muscle and sensing amino acids in the cell is the mechanistic target of rapamycin kinase (mTOR) (3). As we age, mTOR loses its ability to respond to stimulus in the cell (4). This results in an overall reduction in the efficiency of nutrient utilization, also known as metabolic efficiency. A major consequence of this is a reduction of our metabolic potential to harness the energy from our diet, which can lead to lowered energy states in the body. Interestingly, this is an adaptive feature of evolution to minimize cell growth and metabolism as we age, lowering susceptibility to diseases like cancer. Although the body does not want excess growth or metabolic activity, it paradoxically promotes aging.
Our fat cells communicate with each other through hormones they release called adipokines. These fat hormones regulate appetite, energy usage, and nutrient balance. These hormones do not solely exist to increase fat storage, but rather to regulate it. For example, one fat hormone called adiponectin is essential in promoting insulin sensitivity and loss of appetite. Adiponectin also aids in the burning of fat by converting our fat stores (adipocytes) into chemical energy (fatty acids) (4). Variants found in the gene encoding adiponectin (ADIPOQ) strongly correlate with obesity and type 2 diabetes development. In the quest to optimize healthspan, we need to maximize our cells’ capacity to sense nutrients and maintain healthy intercellular communication to promote normative cellular processes.
The age-associated reduction in muscle mass (sarcopenia) increases the risk of frailty, disability, institutionalization, and mortality. Investigating the difference between young and aging muscle tissues helps illustrate the resulting loss of muscle mass and energy capacity. The mitochondria are the cell’s powerhouse and are responsible for generating the universal energy currency of the body, ATP. A 40-50% reduction in the cellular processes that generate ATP has been observed in aging muscle tissue (5). The lowered abundance of ATP has severe consequences, and mitochondrial dysfunction appears to be the central cause. Our cells possess an in-built cell death program to manage any cells that are not functioning correctly, also known as apoptosis. As we age, the increase in mitochondrial damage results in an increase in apoptosis. Elevated rates of cell death along with a decreased rate of mitochondrial regeneration results in a decline in the number of mitochondria in aging muscle tissue (6). Irregular mitochondrial function combined with an overall reduction in mitochondrial number diminishes our ability to generate energy while also producing harmful reactive oxygen species (ROS). Dysregulation of the cell’s powerhouse supports the loss of muscle mass and promotes frailty with aging.
Another major aspect of aging is an overall decline in cognitive function. Most commonly, people first experience this as a reduction in their memory. As we grow older, we start forgetting little things in our daily lives. Maintaining healthy cognitive function into old age is essential for functional independence. Developments in healthcare and medicine over the past century have resulted in drastic increases in lifespan for both men and women. Still, these improvements are also accompanied by an increased incidence of age-associated neurodegenerative dementias. With a rapidly growing elderly population, any insight into the processes that cause cognitive decline could significantly impact the livelihood of millions of Canadians.
Cognition can be separated into two categories, crystallized and fluid abilities (7). Crystallized abilities refer to the abilities to recall and apply information and skills learned in the past, while fluid abilities correspond to cognitive processing at the time of assessment. While crystallized cognitive ability continues to improve until we reach 60, fluid cognitive ability is constantly declining from age 20-80 (8). This decline commonly manifests as reductions in sensory perception (ie. hearing impairment, attention deficit) and cognitive processing, resulting in an overall increase in the time it takes to complete a cognitive task.
Although some of these cognitive declines are a natural part of aging, Alzheimer’s Disease (AD) continues to be the most common cause of the cognitive decline in older adults. Many of the changes associated with AD appear very similar to the processes of natural aging but differ in severity. As previously discussed, energy stores are reduced with age. This also contributes to cognitive decline, as decreases in ATP diminish the neuron’s ability to function properly (5). Deregulated metabolism, a common aspect of age-related decline, promotes the pathogenesis of AD. A primary consequence of this is a decrease in insulin sensitivity in the brain. This explains the increased risk of AD and dementia in diabetes (specifically T2D) individuals (9). Inefficient glucose utilization promotes an oxidative environment resulting in increased protein aggregation. Oxidative damage can also disrupt our DNA and interfere with gene expression leading to impairment of genes essential to maintaining cognitive health. Oxidative damage to lipids (lipid peroxidation) can damage communication between neurons, negatively impacting our capacity to learn and encode memories (9).
Although aging is a universal process, some aspects affect women more than men and vice versa. For example, women undergo a distinct hormonal process called menopause. Menopause encapsulates the transition experienced by women near the time of their last menstrual period signifying a halt in ovulation (10). All women undergo changes in theirphysical and mental health associated with menopause, but some women are affected more than others.
Symptoms associated with menopause can begin several years before the menopausal transition and extend 5 to 8 years past the final menstrual period (11). These symptoms occur primarily due to an imbalance in the body’s sex hormones and can primarily be attributed to an overall decrease in estrogen production. Some things commonly experienced by women during the menopausal transition include hot flashes and chills, sleep disturbances, depressive symptoms like anxiety, panic, and worry vaginal discomfort, and decreased libido (12).
What can we do to protect ourselves from the effects of aging?
Although we cannot avoid aging, there are many things we can do to combat the negative effects and promote good health into old age.
Sleep: Studies have shown that sleep loss contributes to an overall increase in inflammatory markers (13). Sleep impacts many aspects of our physical and mental well-being, and improving sleep quality can have a range of positive outcomes on our health. There is also a significant amount of evidence to support that getting around 7-8 hours of sleep per night can benefit combating cognitive decline with age (14).
Exercise: Consistent aerobic activity can greatly reduce age-associated inflammation, improve insulin sensitivity, lower all-cause mortality, and reduce the overall risk for chronic disease (15). In addition, studies have shown that regular aerobic exercise can help maintain healthy mitochondrial function as we age. Strength training is also important to provide a stimulus to the body, signalling the need to maintain or increase muscle mass and reducing frailty. In addition, exercise has been shown to reduce cognitive decline. Some studies have even shown that it can improve cognitive components such as sustained attention, visual memory, and frontal cognitive function, showing promise as a tool for slowing the progression of Alzheimer’s disease (16). Exercise can also improve bone and joint health, decrease stress, and improve sleep, all major symptoms of hormonal changes that occur with age.
Diet and supplementation: Our diet and feeding schedule can significantly impact age-related inflammation, which is linked to many aspects of aging. For example, studies have shown that intermittent fasting can help alleviate gut-associated inflammation and result in an overall reduction in inflammatory markers in the blood (17). Maintaining a diet rich in omega-3 fatty acids and fiber and limiting the consumption of processed carbohydrates are factors that have also been shown to have positive effects on reducing inflammation. Reducing inflammation can reduce the risk for chronic disease and combat the effects of chronic pain associated with aging. Omega-3 fatty acids are most commonly found in marine-based food sources and are an essential part of our diet as we cannot produce them ourselves. It can be challenging to obtain a substantial amount of Omega-3s from our diet unless we regularly consume fish. Omega-3s can be obtained through supplementation and can help combat multiple aspects of aging. Increasing the amount of omega-3 relative to omega-6 fatty acids has been shown to improve whole-body glucose tolerance, which combats the age-related decline in insulin sensitivity (18). This supplement can also reduce muscle protein breakdown by supporting anabolic signaling, lowering susceptibility to sarcopenia (19).
As we age, there are clear signs and symptoms that we will all experience, but do we have to? Aging is inescapable, but fortunately, there is no shortage of science-based tools at our disposal to promote a healthy lifestyle and maintain good health into old age. Although it may not be possible to completely counter the effects of aging, we have the power to greatly impact our mental and physical well-being as we age and do the things we love for as long as possible. Starting to incorporate healthy lifestyle habits as early as possible can help us stay ahead of the curve and delay the onset of age associated decline. Although aging may be a daunting journey, we can work to optimize our mind and body and facilitate a happy and healthy transition.
The emergence of Precision Medicine, an approach for predicting, preventing and treating disease, and, of equal importance, maximizing health and wellness aiming for healthspan, shows that living longer is not enough, we can live better! At Preventous, we focus on proactive and personalized care that empowers people to lead healthy lives, and that is why, in 2022, we are launching an exciting project for those who are interested in a longer life but also in an extended healthspan. To learn more and be the first to hear about Precision Medicine, visit this page and sign up for the newsletter.
Dr. Rohan Bissoondath,