Preventing Functional Decline with Age: Biomarkers and Best Practices

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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Preventing Functional Decline with Age:
Biomarkers and Best Practices
Matthew Halma and Paul Marik *
Posted Date: 12 March 2024
doi: 10.20944/preprints202403.0667.v1
Keywords: aging populations; healthy aging interventions; physiological changes; autonomy, well-being
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Article
Preventing Functional Decline with Age: Biomarkers
and Best Practices
Matthew Halma 1 and Paul Marik 2,*
1 EbMC Squared CIC, Bath, BA2 4BL, UK; e-mail@e-mail.com
2 Frontline Covid-19 Critical Care Alliance, Washington D.C., USA, 20036; pmarik@flccc.net
* Correspondence: pmarik@flccc.net
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.
Keywords: aging populations; healthy aging interventions; physiological changes; autonomy and
well-being
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].
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
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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 Dail y Living (ADL), as well as be able to perform a thletically 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.
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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 [61–63]. Endurance exercise also prevents cognitive decline in older adults [64].
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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
Musculoskel
tal
Grip Strength [65] Weightlifting Increase in
muscle mass and
bone density
Endurance
training
Lower VO2
max
Metabolic,
cardiopulmo
nary
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
Musculoskel
etal, 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]
Musculoskel
etal,
tendons,
fascia
Flexibility tests: Flexindex [71] Yoga, Pilates Improved
flexibility and
stability
Preservatio
n 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]
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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.
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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 [111–113]. 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 [123–125].
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.
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]
Sel
f
-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]
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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.
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
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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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