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Preventing Functional Decline with Age: Biomarkers and Best Practices

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11 March 2024

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12 March 2024

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Abstract
The aging populations observed across numerous countries worldwide necessitate a thorough exploration of interventions aimed at promoting healthy aging. As individuals age, they undergo significant physiological changes that impact their functional capacity and often necessitate increased reliance on external support systems. Enhancing the autonomy and well-being of elderly individuals emerges as a critical imperative, serving not only individual interests but also broader societal goals. This review investigates various interventions designed to optimize the health and independence of aging populations, offering insights into effective strategies for promoting healthy aging and mitigating the societal burdens associated with an aging demographic.
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Subject: Public Health and Healthcare  -   Physical Therapy, Sports Therapy and Rehabilitation

1. Introduction

Populations in the developed world are more skewed towards older individuals than at any previous time in history. Extrapolating the current population trends, the over-50 population in the US will increase by 61% between 2020 and 2050 [1]. The number of people in that age range with at least one chronic disease is expected to double in that same time period, and the population of those with two or more chronic conditions is expected to increase by 91% [1].
With significant disease burden in the older population, it falls on the proportionately smaller working age population to sustain economic functions and to care for the elderly people. The ratio of the number of working age people to the number of retirees will increase by approximately 35%, from 23 retirees per 100 working people in 2010 to 31 retirees per 100 working people in 2030 [2]. Put another way, for each retired person in 2010, there were four people working, whereas in 2030, there will be only three.
Healthcare expenditures also vary significantly by age. For a 25-year-old in the US in 2011, healthcare consumption is roughly 8% of GDP per capita, for those 85 and above, healthcare consumption is almost 70% of GDP per capita [3]. A projection of healthcare expenditures up to 2045 in Switzerland predicts that healthcare expenditures as a proportion of GDP in 2045 will increase between 30% and 45% from 2013 levels [4]. These models assume GDP growth in line with current projections, and it should be noted that unless GDP per capita is increasing greater than this rate, then the relative burden per working individual will increase.
In the overall global population, approximately one third of people experience multiple chronic conditions [5]. Developed countries have a higher rate of multimorbidity (38%) compared to low or middle income countries (30%) [1]. Multimorbidity increases by roughly 78% for every decade increase in age, and women have rates of multimorbidity 23% higher than males of the same age category. Those living in lower income neighborhoods also had higher rates of multimorbidity [5].
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Figure 1. Prevalence of (multi)-morbidity in the UK by age group. Source: reproduced from [5].
Figure 1. Prevalence of (multi)-morbidity in the UK by age group. Source: reproduced from [5].
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Table 1. Trends in morbidity in the US adult population between 2020 and 2050 (projected). Table is adapted from [1].
Table 1. Trends in morbidity in the US adult population between 2020 and 2050 (projected). Table is adapted from [1].
Age cohort 2020 2035 2050 Relative change between 2020 and 2050(%)
Population (million)
Total adult population 137 180 221 61%
50–59 years 48 56 69 42%
60–79 years 72 95 112 56%
80 and older 17 30 40 137%
≥1 chronic condition (million)
Adult population 72 114 143 100%
50–59 years 16 18 22 40%
60–79 years 45 71 84 86%
80 and older 11 26 37 244%
Multimorbidity (million)
Adult population 8 12 15 91%
50–59 years 2 2 2 40%
60–79 years 5 7 9 79%
80 and older 1 3 4 203%
Prevalence of ≥1 chronic condition (%) 22% 35% 48% 120%
Prevalence of multimorbidity (%) 2% 4% 5% 111%
Resulting from this, there is a potential tsunami of chronic health conditions associated with age, and a subsequent increase in health care expenditures, already accounting for 17.3 percent of Gross Domestic Product (GDP) [6]. Disease chronicity increases with age in the general population. In 2013, 80% of the US population over the age of 65 had at least one chronic condition [7].
Fortunately, implementing healthy aging strategies can drastically reduce disease burden. Dementia for example, manifests over decades [8], giving the individual power to alter their expected course. A previous estimate for the increase in healthcare expenditures per capita was 30 to 45% between 2013 and 2045 [4]. The authors also proposed a ‘Healthy Ageing’ scenario wherein the increase was only 21%, which is still a considerable challenge, but attainable with increases in worker productivity.
The presence of ‘Blue Zones’ or pockets of high life expectancy, demonstrates that it is possible to successfully create a culture of longevity and health [9]. While popular authors have emphasized aspects of the diet of the people in Blue Zones, particularly them being highly plant-based, what remains similar to them is the primacy of whole foods which are traditional to the region and population [10]. In Okinawa one of the identified Blue Zones, 0.8% of people born during the 1900 birth cohort reached the age of 100 [11], compared to 0.3% in the USA, or 0.1% in the UK [9].
These long-lived populations point to a way of healthy aging, as their elderly population retains a high degree of autonomy and independence in their everyday lives, many still keeping up leisurely activities, reading and sports [12].

2. Metabolism

Poor metabolic function can contribute to a wide variety of illnesses. Those who are metabolically unwell (having metabolic multimorbidity) spend 52% more time as an inpatient in hospitals, have a 36% increased likelihood of not being able to perform activities of daily living (ADL) [13]. Metabolic dysregulation is comorbid with mental health disorders [14], cancer [15,16], neurodegenerative diseases [17,18].
Importantly, metabolic health can be readily changed through a shift in food consumption patterns. Any policy decision to tackle chronic disease must have food policy and agriculture at its core. Ultra processed foods (UPFs) comprise a larger proportion of people’s diet now than before, often for reasons of convenience. These UPFs with an often-poor nutritional profile crowd out whole foods in the diet [19], and consumption is associated with an increased risk of all-cause mortality, cardiovascular disease, hypertension, metabolic syndrome, obesity, depression, cancer, gastrointestinal disorders [20] and frailty among others [21]. Factors positively associated with UPF consumption are male sex, young age, smoking (only significant for females) and living alone [20,22]. UPFs have significant and wide-ranging deleterious impacts on health [23].
Aging decreases resting metabolic rate (RMR), which is partially attributable to losses in fat-free mass (FFM, i.e., muscle and bone), though there is a decline independent of FFM [24]. Additionally central adiposity increases as one ages [25], and metabolic changes occur regularly, leading experts to classify metabolic dysregulation as hallmarks of aging [26]. Excess body fat can also alter hormone balance, as adipose tissue can promote estrogen production [27].
There is also significant crosstalk between metabolic health and brain health, where metabolically unhealthy individuals have lower brain volumes into old age than their metabolically fit counterparts [28]. When it comes to healthy aging, it is important to avoid insulin resistance, as this is a significant predictor of age-related disease [29]. Those who live to ages past 100 (centenarians) have better insulin sensitivity than their counterparts who die at younger ages [30].
Endurance exercise can reduce age-related declines in mitochondrial oxidative capacity in individuals [31]. Overall, it is important to maintain metabolic health throughout one’s lifespan.
As one’s general fitness can be broken down into components of strength, speed, agility, balance, flexibility and more, one’s metabolic health can be operationalized through meaningful metrics.
First, examining function, we would want a metabolic system to extract energy from food, enough to perform all Activities of Daily Living (ADL), as well as be able to perform athletically when required. The food that people eat should grow and repair their bodies and be sufficient to power all of the necessary functions that contribute to the basal metabolic rate (BMR).

2.1. Fatigue

Endurance exercise, as opposed to punctuated, vigorous exercise, involves exerting power over a longer duration of time at a lower intensity than acute bursts. While this would appear to have limited applicability outside of endurance sports, one major desire of people is to have sustained energy throughout the day. Typically, energy levels are high in the morning, low in the early afternoon, and then increase again before dropping again at night. Higher Body mass index and waist circumference are associated with higher levels of fatigue [32].
Most studies of energy levels of people look at those which suffer from fatigue due to an illness, and not quotidian fatigue. Several dietary conditions have been investigated for their effect on fatigue in disease contexts, and some literature exists on the impact of diet on fatigue in the context of physical training.
In chronic fatigue syndrome (CFS), adoptees of a low sugar and low yeast diet decreased their fatigue significantly (p=0.002, difference measured by the Chalder fatigue score) from their baseline measured before the dietary intervention [33].
A study of breast cancer survivors found that fatigue was associated with fat consumption, and negatively associated with carbohydrate and fiber consumption [34]. A meta-analysis on Multiple Sclerosis (MS) related fatigue came to similar conclusions, finding diets high in greens and low in fat [35], such as a modified paleo diet, may improve MS-related fatigue [36]. The meta-analysis also demonstrated low-quality evidence supporting folate and magnesium for decreasing fatigue [37]. Carbohydrate intake is positively associated with physical capacity, while fat consumption is negatively associated with physical performance in a six-minute walk test and VO2max tests [38]. Omega 3 improved VO2 max, and vitamin D was associated with a nonsignificant improvement in VO2max. Paleolithic diets and Mediterranean diets improved fatigue in MS patients [39], as well as anti-inflammatory diets [40].
Chronic fatigue syndrome (CFS) is another condition where people have difficulty with energy levels. A 2017 meta-analysis showed improvements in fatigue for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10[41]. Omega 3, D-ribose, polyphenols and a multivitamin supplement also have support for their therapeutic use in CFS [42,43].
In the case of cancer related fatigue, adoption of the Mediterranean diet was associated with a small-moderate decrease in fatigue levels [44]. High protein [45], carnitine [46,47], Omega-3 [48], American Ginseng [49], Wisconsin Ginseng [50] and Astralagus membranacus [51] reduced fatigue [52]. Guarana had mixed positive effects [53] and nonsignificant effects [54,55].
For weightlifters in the midst of weight loss, high protein consumption helped with fatigue [56]. For non-athletes losing weight, higher vegetable consumption was associated with lower levels of fatigue [57].

3. Cognition

One of the most feared outcomes of aging is a loss of cognition. Many elderly people do suffer from dementia, whether in mild or severe forms. This can be attributed to several mechanisms, some of which can be mediated through diet and lifestyle. First, mitochondrial function often degrades, and aggregates can form in the cases of full-blown Alzheimer’s disease. Other factors include decreased circulation, which can also precipitate hair loss.
As people age, they often become more set in their ways and are less likely to actively learn new things, despite, in retirement, having more leisure time than during their working life. In fact, retirement can have very negative mental health consequences for seniors, as inactivity and seclusion can harm neural pathways.
Furthermore, one commonality in old age is a reduction of one’s social circle, as this often decreases as one increasingly becomes home bound. Old age homes may precipitate some social interaction in the common areas, but this is typically inadequate. Additionally, one social trend acting against senior cognitive health is that parents and children are decreasingly co-located in the same region, making visits more difficult.
The importance of regular social engagement for senior mental health has been studied, showing a significant impact of loneliness on senior health.
This impact often stretches back many years, where those with a more robust friend circle decades earlier also maintain a robust friend circle into old age. Therefore, the social circle is another ‘biomarker’ albeit unconventional, associated with successful aging. Here, relationships should be considered as a vital part of aging, as they present a vital support.
Heart rate variability [58] and vagal nerve tone [59] are important biomarkers for stress tolerance.
Hobbies, including engagement with music [60], are associated with lower rates of cognitive decline and dementia [61,62,63]. Endurance exercise also prevents cognitive decline in older adults [64].
Table 2. Body systems, associated biomarkers and means of training.
Table 2. Body systems, associated biomarkers and means of training.
Training Type Trend (absent training) System Associated tests and biomarkers Training Adaptations
Strength Training Sarcopenia, muscle loss, bone loss Musculoskeltal Grip Strength [65] Weightlifting Increase in muscle mass and bone density
Endurance training Lower VO2 max Metabolic, cardiopulmonary Resting Metabolic Rate, Creatine phosphokinase [66] Running, swimming, walking, cycling, cross-country skiing, hiking, etc. Increased mitochondrial size, greater ability to metabolize fat, increased (heart) stroke volume
Balance training Poorer coordination Musculoskeletal, nervous Self-selected gait velocity [67], Chair rise test (timed 5 chair rises), Tandem standing and walking, timed up and go test, clinical gait analysis with special focus on regularity, mechanography [68] Yoga Neuromuscular control [69]
Flexibility Decrease in joint flexion [70,71] Musculoskeletal, tendons, fascia Flexibility tests: Flexindex [71] Yoga, Pilates Improved flexibility and stability
Preservation of genomic integrity Accumulation of mutations [72], accumulation of methylation, higher cancer rates [73] Genomic
Integrity		 Telomere Length [74], Methylation level [75] Low inflammation practices, avoiding carcinogenic exposures, possibly fasting [76] Low inflammation practices, avoiding carcinogenic exposures, possibly fasting [76]
Cognition Impairment on task switching [78], working and long-term memory [78] Nervous Cognitive tests [79]:
Mini-Mental State Examination, Isaacs Set Test,
Benton Visual Retention Test,
Digit Symbol Substitution Test [80], Combined panel [81]		 Equivocal evidence for transfer effects of cognitive training [82],
Combined program (exercise, brain training and lecture) [83],
Reading [84],
Hobbies [85],
Multilingualism [86],
Dance [87],
Social Activity [88],
meditation [89]		 Increased BDNF and neurogenesis [90] preservation of white matter

4. Cardiovascular and Pulmonary Health

Heart stroke volume from the heart increases with age, while heart rate decreases [91]. Maximum heart rate also decreases with age [92].
While total lung volume remains constant [93], respiratory strength decreases with age [94]. Aging causes a change in deep breathing where deep breathing is less able to increase the size of peripheral airways [95]
In addition, breath volume decreases with age, unless it is countervailed by physical activity.
Endurance exercise is excellent for aging people, as endurance exercise improves mitochondrial density [96] by enlargement of existing mitochondria [97,98].
Can keep increasing, even as one grows older. The impacts of endurance exercise are cumulative, and people with histories of endurance exercise retain their endurance into advanced age.
Cardiopulmonary health can be assessed by the VO2 max test, which involves finding the maximal level of exertion and measuring the flow of oxygen at this level. VO2 max typically decreases with age, dropping more modestly in exercising individuals [99,100].
Given the trend of decreases in heart stroke volume and heart rate with increasing chronological age, VO2 max also declines with age, as it measures the combination of these factors along with respiratory capacity. It is important to retain VO2 max as one ages, and VO2 max helps with capacity to perform daily actions, such as walking up stairs. Additionally, endurance exercise also provides the metabolic benefits of increased mitochondrial density.
Another means by which older adults can improve their metabolic parameters is by cold exposure, which can facilitate the conversion of white adipose tissue to more metabolically active brown adipose tissue (BAT). This increases one’s basal metabolic rate and the practice can also improve one’s tolerance to cold. Older people, especially women, often feel cold at higher temperatures than their younger and male counterparts, so intentional cold exposure can help to alleviate this.
In addition to the cognitive benefits espoused above, periodic fasting can be important for metabolic parameters as well as improving cognitive function. Regular fasting can help to reduce blood sugar variation, which is a contributor to neurodegenerative diseases.
One common intervention that elderly people use is oxygen support. Approximately 1 in 5 people over the age of 70 have some form of chronic obstructive pulmonary disease [101]. Breathing pattern can impact the rates of respiratory illness, with mouth breathing contributing to the development of respiratory disorders [102,103]. One simple means of improving breathing performance is the practice of mouth taping, which involves taping one’s mouth shut during sleep, preferably using a tape that does not leave a residue. Participants in a study experienced significant improvements in rates of snoring and decreases in rates of apnoea events [104].
Ideally, in healthy aging we would prevent the need for supplementary oxygen. Being on cannula oxygen is often bulky and cumbersome, though newer models have reduced the mass to <10lbs (~3kg) [105].

5. Musculoskeletal (Strength and Stability)

Musculoskeletal fitness and stability are very important for older individuals to maintain their independence and sovereignty as they age. Without their own mobility, they are dependent on a caregiver, either paid, a family or friend, for their transportation needs. Paid caregivers can be financially taxing, and the relational caregivers may strain the relationship if one asks too often, creating resentment.
Hip fractures are a major reason for senior death, the one-year mortality after a hip fracture is 24% [106]. Additionally, the sense of autonomy ties into many other positive health circuits. If one is mobile, they can reap the benefits of exercise and the outdoors. If people are left indoors without social interaction, an extreme case being solitary confinement, mental health degrades quickly, and physical deterioration is fast.
Generally, after a certain age, muscle mass declines by a few percentage points per year [107,108]. This can be combatted through resistance training to increase muscle mass and improve both stability (to prevent falls) and strength (to resist injury in the case of falls). Vitamin D is associated with musculoskeletal strength [109] and may be an important intervention for maintaining strength in old age.

6. Emotional Health for Aging

Maintaining a positive life outlook throughout times of stress is associated with decreases in inflammation and future depressive symptom onset [110], additionally, an optimistic spirit is associated with healthier behaviours [111,112,113]. Optimism is a significant predictor of positive health outcomes [114], and improved quality of life in individuals experiencing disease [115]. Optimism can also have a positive impact on people close to the optimistic individual, as a spouse’s optimism is associated with the health of the other spouse [116]
Holding onto regret is a factor in lowered psychological well-being in the aged [117,118], thought the emotional salience of missed opportunities is lesser in older people as opposed to young [119]. Forgiveness is also associated with increased well-being [120,121], including forgiveness of self- [122].
Expressing and feeling gratitude is associated with life satisfaction [123,124,125].
The ‘Big Five’ personality traits include openness, agreeableness, extraversion, conscientiousness, and neuroticism. Of these traits, extraversion [126,127], conscientiousness [128] and openness [129] have been positively associated with life satisfaction. The impact of agreeableness is more heterogenous, and it may have a negative impact on life satisfaction [130]. Neuroticism is associated with lower levels of subjective well-being [127].
Table 3. Psychological factors for fulfillment in later life.
Table 3. Psychological factors for fulfillment in later life.
Factor Interventions
Regret Reflect and change behaviour going forward [131]
Create positive life experiences
Gratitude Express, journal [132]
Forgiveness Reflecting on events, moving from resentment to compassion [133]
Openness Explore, try new things [134]
Meaning/Purpose Intrinsic Motivation Life crafting [135]
Conscientiousness Adhere to a program [136]
Belongingness Connect [137]
Self-transcendence Experience flow [138]
One significant cause of reduced quality of life in older people is a lack oof emotional health, sense of purpose and connection. Emotional, spiritual, and relational health are important aspects that are often neglected in favor of more salient and quantifiable changes in the body. Aging often marks the point at which people retire, and so no longer have their daily work to provide them meaning. Often, if people do not find a sense of meaning in what they do day to day, their health suffers and deteriorates quite rapidly after retirement.
It is important to occupy oneself with hobbies which are engaging. Ideally, one could develop these before retirement, and allow them to take up a larger portion of one’s focus and energy. However, the concept of retirement, is a modern invention, which only really existed from about the 1950s to today, as older people, while they may not be working if their younger counterparts, still engaged themselves in mentorship and community activities well into their later years.
The ubiquitous reliance on old age care homes has also been a modern invention, with relative overlap with the development of retirement as a social phenomenon. Within care homes, conditions vary, though these are almost universally seen as less preferable to independent living, and often undermine the autonomy of older individuals through rules and restrictions on movement, for example.
Most residents of care homes have some form of cognitive impairment [139,140], and cognitive decline accelerates in nursing homes as opposed to more independent living [141,142]. This trend was worsened during the pandemic restrictions [143]. Elderly people in residential care or assisted living facilities have lower rates of depression and higher social functioning than their counterparts in nursing homes with less independence [144]
Often in aging, when one’s capabilities begin to decline, this causes psychological pain; this can also be exacerbated by the attitudes of caregivers which may reinforce the supposed helplessness of those advanced in age [145]. Caregivers employed by old age care homes are paid poor wages and often lack the motivation to enable autonomy of those in their care [146], cultural misunderstandings may occur between residents and care home employees [147].

7. Resiliency in Aging

In prior eras, the care of the elderly would have come to the family, lacking that, the elderly lacking cognitive ability would have been destitute or been in the care of the community institutions, which could mean the church or poorhouses, the forerunners to current public old age homes [148]. Life would have been difficult for the aged lacking physical capability, though lifespans were significantly shorter, and there was often a shorter gap between health span (length of healthy life) and lifespan (length of life) [149]. This can partly be attributed to medical care, which allowed people to survive despite chronic illnesses, and economic prosperity, which allowed elderly people to exist as non-productive members of society.
The experience of older people in care homes is generally more negative than that in independent living, provided the elder retains autonomy in the latter case [150]. Examining the social determinants of health, it is also very important that older adults consider their financial health, to enable themselves to live independently well into their later years. Poor financial earnings are associated with higher rates of dementia [151], and dementia can further aggravate one’s financial issues [152]. Furthermore, those with limited financial resources have fewer options for treatment and long-term care, and this negatively impacts their prognosis.
Within the framework of permaculture, it is presented the 8 forms of capital, which include [153]:
(1)
Financial
(2)
Living
(3)
Material
(4)
Knowledge
(5)
Emotional and Spiritual
(6)
Social
(7)
Cultural
(8)
Time.
Table 4. Types of Capital and their relationship with healthy aging.
Table 4. Types of Capital and their relationship with healthy aging.
Type of Capital Explanation Relationship with healthy aging Interventions
Financial One’s financial resources Financial health associated with lower rates of dementia, and better outcomes in case of dementia [152] Saving, Investing, Increasing Earning Potential
Living One’s natural surroundings Surrounding green space associated with lower dementia risk [154,155] Gardening, planting trees, regenerative agriculture/silviculture
Knowledge One’s knowledge base and skillset Lifelong learning associated with lower risk of dementia [156] Learning, Hobbies
Emotional and Spiritual One’s personal faith Religious attendance associated with lower dementia risk [157,158] Religious and spiritual practice, prayer, meditation
Social One’s connections with other people Loneliness associated with dementia [159] Social activity
Cultural Values and traditions Frequent family visits associated with decrease in dementia symptoms [160] Story Telling
Time Capital One’s time remaining Age associated with dementia [161] Maximize health span, leave unfulfilling time obligations, optimize practices, delegate

8. Conclusions

Addressing the challenges posed by aging populations requires a holistic approach encompassing various facets of health and well-being. The review underscores the importance of enhancing autonomy and well-being among the elderly to achieve individual and societal goals. Interventions targeting metabolic health, endurance exercise, dietary patterns, and cognitive engagement emerge as crucial strategies for promoting healthy aging. The interconnectedness of factors such as cardiovascular health, musculoskeletal fitness, and emotional well-being is highlighted, emphasizing the need for a comprehensive perspective. Beyond biomedical markers, the paper recognizes the significance of emotional health, social connections, and a sense of purpose in determining overall well-being. Exploring different forms of capital further underscores the diverse aspects influencing the aging process, including financial, living, knowledge, emotional and spiritual, social, cultural, and time capital. The paper advocates for proactive measures, family support, and community engagement to foster resilience in aging, ultimately contributing to healthier and more fulfilling lives for the elderly.

Author Contributions

Conceptualization, M.T.J.H. and P.E.M.; writing—original draft preparation, M.T.J.H.; writing—review and editing, P.E.M and M.T.J.H.

Funding

This research is funded by donations to the Frontline Covid-19 Critical Care Alliance (FLCCC).

Acknowledgments

We thank donors to the FLCCC Alliance.

Conflicts of Interest

The authors declare no conflicts of interest.

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