The Science of Aging

Why do we age?

This question may seem simple, but it has a complex answer. Natural selection favours the most successful genes, which means that the individuals carrying those genes must also survive long enough to reproduce. Therefore, if surviving and reproducing is so important, why don’t we live forever and not age at all?

Antagonistic pleiotropy is currently the best-accepted theory for aging. It was first proposed by George C. Williams in 1957.¹Williams GC. Pleiotropy, Natural Selection, and the Evolution of Senescence. Evolution. 1957;11; 398–411. doi: 10.2307/2406060. In his theory, the alleles (variations of a specific gene) that increase fitness and reproduction also cause destruction later in life. Hence the name antagonistic pleiotropy, where ‘antagonistic’ means against, and ‘pleiotropy’ means a single gene having two or more phenotypes (an individual’s observable physical traits).

The phenomenon of antagonistic pleiotropy occurs at both a population level and an individual level. At a population level, a combination of high fertility and a long lifespan may seem like an excellent idea for individuals, but it has dangerous consequences for a population as it may cause collapse. This has been tested in computer models where the combination of a long lifespan and high fertility produces short-term, large populations, followed by local extinction.²Mitteldorf J. What Is Antagonistic Pleiotropy? Biochemistry (Mosc). 2019;84; 1458-1468. doi: 10.1134/S0006297919120058.

Within an individual, there are biological trade-offs, for example, early reproduction may compromise immune function, leading to a shortened lifespan. This example is seen in Western gulls, common eider sea ducks, and drosophila.³Austad SN, Hoffman JM. Is antagonistic pleiotropy ubiquitous in aging biology? Evol Med Public Health. 2018;2018; 287-294. doi: 10.1093/emph/eoy033.

Aging is caused by unavoidable trade-offs. The resources within an individual or in an environment are finite, and it is therefore impossible to continue living forever.

Lifespan vs. healthspan

Lifespan is the total number of years that we can live. Healthspan, on the other hand, refers to the number of quality years one can live, not just the total number of years. This is important because there is little yield in living until 100 years of age if the last 20 years are lived in misery from chronic illness. Therefore, healthspan incorporates an important metric used in medicine called quality-adjusted life year (QALY).⁴Weinstein MC, Torrance G, McGuire A. QALYs: the basics. Value Health. 2009;12 Suppl 1; S5-9. doi: 10.1111/j.1524-4733.2009.00515.x. One QALY equates to one year in perfect health and ranges from 1 (perfect health) to 0 (dead).

The goal is to have as long a lifespan as possible with as many of those years in good health as possible.

Although one cannot live forever, the science of aging posits that aging is modifiable and that it is possible to alleviate age-related diseases and extend longevity. To do so, we must understand the mechanisms of aging and the factors that accelerate or prevent it.

Centenarians

Centenarians are people who have lived to 100 years of age or more. They provide an excellent insight into maximising healthspan and lifespan. A common feature that centenarians have is that they live most of their lives without disease. They succumb to the same illnesses that all humans do, but this occurs about 30 years later. In other words, they “time shift” these illnesses to later in life, and when they occur, it is for a shorter period.⁵Borras C, Ingles M, Mas-Bargues C, Dromant M, Sanz-Ros J, Roman-Dominguez A, et al. Centenarians: An excellent example of resilience for successful ageing. Mech Ageing Dev. 2020;186; 111199. doi: 10.1016/j.mad.2019.111199.

What are the hallmarks of normal aging?

Aging is characterised as a progressive loss of physiological function, leading to frailty and eventually death. However, broad-term definitions like this lack the granularity required to understand aging in detail.

The biochemical (molecular) processes of aging

There are twelve cellular and molecular hallmarks of aging.⁶Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023;186; 243-278. doi: 10.1016/j.cell.2022.11.001.

These hallmarks underscore the intricate nature of aging, which encompasses various molecular, genetic, and biochemical processes. It is also crucial to recognise the interconnectedness of these hallmarks, as they interact with each other and contribute to physiological dysfunction and frailty. A comprehensive understanding of these hallmarks gives us insight into the mechanisms of aging, which opens up avenues for potential interventions.

The role of genetics

Several studies have confirmed the commonly accepted notion that genetics play a significant role in the process of aging. Overall, this effect is estimated at about 25%.⁷vB Hjelmborg J, Iachine I, Skytthe A, Vaupel JW, McGue M, Koskenvuo M, Kaprio J, Pedersen NL, Christensen K. Genetic influence on human lifespan and longevity. Hum Genet. 2006 Apr;119(3):312-21. doi: 10.1007/s00439-006-0144-y

The aging effects on different body systems

The effects of aging are generally predictable, however, different organs and body systems progress at different rates. This varied progression leads to age-related diseases and deterioration at different times. The changes that occur with aging are influenced by a multitude of components, including genetics, lifestyle, and environmental factors.

While our understanding has improved significantly over recent years, there is still a lot we don’t know. So, what do we know?

Physiology

Physiology relates to the functions and mechanisms of the body. This includes the daily rhythms, and control of various body systems such as fluid balance, blood pressure, sleep cycles, and temperature control.

The secretion of a range of hormones is decreased with aging, this includes the sex hormones, growth hormone, melatonin, and the hormones controlling the thyroid and adrenal glands.⁸Veldhuis JD. Altered pulsatile and coordinate secretion of pituitary hormones in aging: evidence of feedback disruption. Aging (Milano). 1997;9(4 Suppl):19-20. doi: 10.1007/BF03339688

Aging causes an “internal phase drift” resulting in older people needing to sleep about two hours earlier than young adults.

Various body system reserves reduce with age and compromise resilience. This means an individual is more susceptible to disease, injury, and shocks/insults.

Blood and immune systems

Bone marrow and the blood system’s capacity to produce blood cells declines with age. However, there are enough reserves to keep up with normal requirements. Nonetheless, when there is a significant insult to this system (e.g., with blood loss), recovery times are prolonged due to the loss of this production capacity.⁹Sansoni P, Cossarizza A, Brianti V, Fagnoni F, Snelli G, Monti D, Marcato A, Passeri G, Ortolani C, Forti E, et al. Lymphocyte subsets and natural killer cell activity in healthy old people and centenarians. Blood. 1993 Nov 1;82(9):2767-73^,10Kirkland JL, Tchkonia T, Pirtskhalava T, Han J, Karagiannides I. Adipogenesis and aging: does aging make fat go MAD? Exp Gerontol. 2002 Jun;37(6):757-67. doi: 10.1016/s0531-5565(02)00014-1^,11French RA, Broussard SR, Meier WA, Minshall C, Arkins S, Zachary JF, Dantzer R, Kelley KW. Age-associated loss of bone marrow hematopoietic cells is reversed by GH and accompanies thymic reconstitution. Endocrinology. 2002 Feb;143(2):690-9. doi: 10.1210/endo.143.2.8612^,12Boggs DR, Patrene KD. Hematopoiesis and aging III: Anemia and a blunted erythropoietic response to hemorrhage in aged mice. Am J Hematol. 1985 Aug;19(4):327-38. doi: 10.1002/ajh.2830190403^,13Veldhuis JD. Altered pulsatile and coordinate secretion of pituitary hormones in aging: evidence of feedback disruption. Aging (Milano). 1997;9(4 Suppl):19-20. doi: 10.1007/BF03339688

Furthermore, genetic errors can increase the risk of various blood system cancers. A range of changes in the coagulation system promote clotting in older people, increasing the risk of abnormal blood clots and deep-vein thrombosis (DVT).

Gastrointestinal system

There are minimal impacts on the gastrointestinal system, however, there are some:

• Mucosa thins with age, and dentition deteriorates.¹⁴Hall KE, Proctor DD, Fisher L, Rose S. American gastroenterological association future trends committee report: effects of aging of the population on gastroenterology practice, education, and research. Gastroenterology. 2005 Oct;129(4):1305-38. doi: 10.1053/j.gastro.2005.06.013
• Dry mouth is common due to a 50% reduction in saliva production.¹⁵Smith CH, Boland B, Daureeawoo Y, Donaldson E, Small K, Tuomainen J. Effect of aging on stimulated salivary flow in adults. J Am Geriatr Soc. 2013 May;61(5):805-8. doi: 10.1111/jgs.12219
• Absorption of most nutrients decreases slightly but is still adequate for normal functioning.¹⁶Saltzman JR, Russell RM. The aging gut. Nutritional issues. Gastroenterol Clin North Am. 1998 Jun;27(2):309-24. doi: 10.1016/s0889-8553(05)70005-4
• Liver function to declines by 30% to 50% with age.¹⁷Wynne HA, Cope LH, Mutch E, Rawlins MD, Woodhouse KW, James OF. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology. 1989 Feb;9(2):297-301. doi: 10.1002/hep.1840090222

Renal (kidney) system

Kidney function drops by about 50% by the age of 70.¹⁸Denic A, Lieske JC, Chakkera HA, Poggio ED, Alexander MP, Singh P, Kremers WK, Lerman LO, Rule AD. The Substantial Loss of Nephrons in Healthy Human Kidneys with Aging. J Am Soc Nephrol. 2017 Jan;28(1):313-320. doi: 10.1681/ASN.2016020154 This means that older people are unable to maintain water balance or remove toxins from the body as effectively as healthy young people. Furthermore, older kidneys tend to ‘leak’ more amino acids and sodium.¹⁹Sands JM. Urine concentrating and diluting ability during aging. J Gerontol A Biol Sci Med Sci. 2012 Dec;67(12):1352-7. doi: 10.1093/gerona/gls128

The kidney’s declining function impacts the vitamin D synthesis pathway, contributing to lower levels in older people. There is also reduced production of the protein Klotho, which is believed to have anti-aging properties.²⁰Arking DE, Krebsova A, Macek M Sr, Macek M Jr, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):856-61. doi: 10.1073/pnas.022484299

Cardiovascular system

While strictly speaking, it is not a change of aging, atherosclerosis is present in 75% of men from the age of 50, and in women from the age of 70.²¹White KE, Edwareds JE, Dry TJ. The Relationship of the Degree of Coronary Atherosclerosis with Age, in Men. Circulation. 1950 Apr 1;1(4):645-54. doi: 10.1161/01.CIR.1.4.645 This can have a significant impact on blood flow to the organs and systems of the body.

There are age-related physiologic impairments that affect heart function overall, however, due to compensation, this has little impact on the body at rest. Nonetheless, when the system is stressed, impaired function becomes obvious. This could also reflect the natural decline in physical exercise, capacity and fitness with age, rather than the aging processes.²²Fleg JL, O’Connor F, Gerstenblith G, Becker LC, Clulow J, Schulman SP, Lakatta EG. Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women. J Appl Physiol (1985). 1995 Mar;78(3):890-900. doi: 10.1152/jappl.1995.78.3.890

Respiratory system

Aging results in a reduction in the ability to transfer oxygen from the air into the blood. This is caused by anatomical changes, mismatches between air and blood flow, and a loss of collagen and elastin that results in a reduction of surface area. Increasing stiffness of the chest wall, combined with reduced efficacy of the diaphragm, makes breathing harder with age.²³Janssens JP. Aging of the respiratory system: impact on pulmonary function tests and adaptation to exertion. Clin Chest Med. 2005 Sep;26(3):469-84, vi-vii. doi: 10.1016/j.ccm.2005.05.004

Genitourinary system

Incontinence is very common among older individuals. This is thought to be due to a combination of reduced pelvic floor muscle efficacy, reduced innervation of these muscles, and reduced levels of dopamine in the brain.²⁴Gilpin SA, Gilpin CJ, Dixon JS, Gosling JA, Kirby RS. The effect of age on the autonomic innervation of the urinary bladder. Br J Urol. 1986 Aug;58(4):378-81. doi: 10.1111/j.1464-410x.1986.tb09089.x^,25Tadic SD, Griffiths D, Schaefer W, Murrin A, Clarkson B, Resnick NM. Brain activity underlying impaired continence control in older women with overactive bladder. Neurourol Urodyn. 2012 Jun;31(5):652-8. doi: 10.1002/nau.21240^,26Haddad R, Panicker JN, Verbakel I, Dhondt K, Ghijselings L, Hervé F, Petrovic M, Whishaw M, Bliwise DL, Everaert K. The low dopamine hypothesis: A plausible mechanism underpinning residual urine, overactive bladder and nocturia (RON) syndrome in older patients. Prog Urol. 2023 Mar;33(4):155-171. doi: 10.1016/j.purol.2023.01.002

The reduction of oestrogen in women impacts the natural bacterial barrier function, increasing the risk of contamination and infections.²⁷Dubeau CE. The aging lower urinary tract. J Urol. 2006 Mar;175(3 Pt 2):S11-5. doi: 10.1016/S0022-5347(05)00311-3

Oestrogen replacement (typically creams) can reduce the aging effects of the urinary system in women. Pelvic floor exercise is also helpful.²⁸Capobianco G, Donolo E, Borghero G, Dessole F, Cherchi PL, Dessole S. Effects of intravaginal estriol and pelvic floor rehabilitation on urogenital aging in postmenopausal women. Arch Gynecol Obstet. 2012 Feb;285(2):397-403. doi: 10.1007/s00404-011-1955-1

Musculoskeletal system

There is a significant loss of muscle mass (40%) and strength with age, and increasing loss is a predictor of mortality. This is partly due to infiltration with fat but also to reduced innervation of the muscle fibres. This also contributes to impaired control and responsiveness of the muscles. ²⁹Faulkner JA, Larkin LM, Claflin DR, Brooks SV. Age-related changes in the structure and function of skeletal muscles. Clin Exp Pharmacol Physiol. 2007 Nov;34(11):1091-6. doi: 10.1111/j.1440-1681.2007.04752.x^,30Watanabe K, Holobar A, Kouzaki M, Ogawa M, Akima H, Moritani T. Age-related changes in motor unit firing pattern of vastus lateralis muscle during low-moderate contraction. Age (Dordr). 2016 Jun;38(3):48. doi: 10.1007/s11357-016-9915-0 Age-related changes in growth hormones and androgens also contribute.

Older muscles become fatigued more easily, and recovery from injury is much slower.

Several components of aging result in bone loss, and this is worse for women after menopause. This includes increased bone resorption and reduced bone production. Structural bone changes also make them weaker, resulting in slower healing after injury.

Vitamin D, parathyroid hormone, vascular endothelial growth factor (VEGF), calcium supplementation, and statins can help with bone healing – both fractures and micro-cracks.³¹Gruber R, Koch H, Doll BA, Tegtmeier F, Einhorn TA, Hollinger JO. Fracture healing in the elderly patient. Exp Gerontol. 2006 Nov;41(11):1080-93. doi: 10.1016/j.exger.2006.09.008

Central nervous system

With age, the brain loses neurons, its size decreases, and it accumulates compounds such as senile plaques and tangles.³²Driscoll I, Davatzikos C, An Y, Wu X, Shen D, Kraut M, Resnick SM. Longitudinal pattern of regional brain volume change differentiates normal aging from MCI. Neurology. 2009 Jun 2;72(22):1906-13. doi: 10.1212/WNL.0b013e3181a82634^,33Salat DH, Kaye JA, Janowsky JS. Prefrontal gray and white matter volumes in healthy aging and Alzheimer disease. Arch Neurol. 1999 Mar;56(3):338-44. doi: 10.1001/archneur.56.3.338 By age 85, compounds have accumulated so much that 50% would meet the criteria for Alzheimer’s disease.³⁴Corrada MM, Berlau DJ, Kawas CH. A population-based clinicopathological study in the oldest-old: the 90+ study. Curr Alzheimer Res. 2012 Jul;9(6):709-17. doi: 10.2174/156720512801322537

Brain neurotransmitters also decline with age which may contribute to impaired cognitive performance.³⁵Chowdhury R, Guitart-Masip M, Lambert C, Dayan P, Huys Q, Düzel E, Dolan RJ. Dopamine restores reward prediction errors in old age. Nat Neurosci. 2013 May;16(5):648-53. doi: 10.1038/nn.3364

Cognitive Function and Problem Solving

Cognitive function declines with age, however, not all areas are significantly affected. The biggest impacts are on memory and executive function. Executive function is a set of skills that provide the capacity to self-control behaviour and plan & achieve long-term goals.³⁶Cabeza R, Nyberg L, Park DC. Cognitive neuroscience of aging linking cognitive and cerebral aging. Oxford: Oxford University Press; 2005. This can have an impact on people’s ability to plan and manage their daily lives.

Problem-solving, processing, learning, and attention span also decrease, particularly in busy, distracting environments.³⁷Yang AC, Huang CC, Yeh HL, et al. Complexity of spontaneous BOLD activity in default mode network is correlated with cognitive function in normal male elderly: a multiscale entropy analysis. Neurobiol Aging. 2013;34(2):428-438. doi:10.1016/j.neurobiolaging.2012.05.004^,38Harada CN, Natelson Love MC, Triebel KL. Normal cognitive aging. Clin Geriatr Med. 2013;29(4):737-752. doi:10.1016/j.cger.2013.07.002

Improving Cognitive Performance

Supplementing with dopamine in otherwise normal older people can improve cognitive performance.³⁹Chowdhury R, Guitart-Masip M, Lambert C, Dayan P, Huys Q, Düzel E, Dolan RJ. Dopamine restores reward prediction errors in old age. Nat Neurosci. 2013 May;16(5):648-53. doi: 10.1038/nn.3364

Cognitive training exercises can slow the cognitive decline and can even increase the size of the brain.⁴⁰Ball K, Edwards JD, Ross LA. The impact of speed of processing training on cognitive and everyday functions. J Gerontol B Psychol Sci Soc Sci. 2007;62 Spec No 1:19-31. doi:10.1093/geronb/62.special_issue_1.19^,41Engvig A, Fjell AM, Westlye LT, et al. Effects of cognitive training on gray matter volumes in memory clinic patients with subjective memory impairment. J Alzheimers Dis. 2014;41(3):779-791. doi:10.3233/JAD-131889

Skin

There are two major age-related, degenerative impacts on the skin. They are known as ‘true aging’ and ‘photoaging‘ which are caused by the effects of sun exposure.

Aging of the skin results in atrophy, reduced elasticity, fragility, dry skin, and impaired repair. Atrophy results in the thinning of both the epidermis and dermis. Collagen in the dermis is reduced by as much as 75%.⁴²Russell-Goldman E, Murphy GF. The Pathobiology of Skin Aging: New Insights into an Old Dilemma. Am J Pathol. 2020;190(7):1356-1369. doi:10.1016/j.ajpath.2020.03.007

Photoaging

Photoaging, due to chronic sun exposure, results in many changes such as reduced collagen, elastin, increased wrinkling, and spotty skin.

Sensory system

Aging results in several changes to the eyes. The most significant are a loss of fluid in the eye as well as increased in rigidity. The retina also loses neural tissue. This brings on a reduced ability to focus on near objects and a reduced ability to see moving objects (also known as presbyopia). The ability to see contrast also decreases.⁴³Strenk SA, Strenk LM, Koretz JF. The mechanism of presbyopia. Prog Retin Eye Res. 2005;24(3):379-393. doi:10.1016/j.preteyeres.2004.11.001^,44Wang JH, Wong RCB, Liu GS. Retinal Aging Transcriptome and Cellular Landscape in Association With the Progression of Age-Related Macular Degeneration. Invest Ophthalmol Vis Sci. 2023;64(4):32. doi:10.1167/iovs.64.4.32

Aging impairs the ability to hear high-frequency sounds and impacts speech recognition, particularly in noisy environments.⁴⁵Martin JS, Jerger JF. Some effects of aging on central auditory processing. J Rehabil Res Dev. 2005;42(4 Suppl 2):25-44. doi:10.1682/jrrd.2004.12.0164

Aging reduces taste sensitivity by about 30%. However, this is largely related to impaired smell with aging which reduces by about 50%.⁴⁶Mojet J, Christ-Hazelhof E, Heidema J. Taste perception with age: generic or specific losses in threshold sensitivity to the five basic tastes?. Chem Senses. 2001;26(7):845-860. doi:10.1093/chemse/26.7.845^,47Gudziol H, Hummel T. Normative values for the assessment of gustatory function using liquid tastants. Acta Otolaryngol. 2007;127(6):658-661. doi:10.1080/00016480600951491^,48Boyce JM, Shone GR. Effects of ageing on smell and taste. Postgrad Med J. 2006;82(966):239-241. doi:10.1136/pgmj.2005.039453

Immune system

The immune system’s function also reduces with age. The biggest impacts on the immune system are:

• Its ability to generate an effective immune response and memory to new antigens, whether from infection or vaccination.
• Its ability to self-regulate the inflammatory process that leads to ongoing, low-level chronic inflammation.
• The outcomes of this are an increased risk of infection, autoimmune diseases, and various cancers.

Strategies to slow aging

While the effects of aging are most outwardly visible on the skin, having a good foundation can help optimise the appearance of the skin. In particular, structural components such as bone and muscle have the biggest impacts.

What can we do to slow the aging process?

The ideal candidate to slow the aging process would target all 12 hallmarks of aging. To date, one intervention appears to do this effectively: exercise. The impact of exercise has been examined in both animal and human models of aging.⁴⁹Rebelo-Marques A, De Sousa Lages A, Andrade R, Ribeiro CF, Mota-Pinto A, Carrilho F, et al. Aging Hallmarks: The Benefits of Physical Exercise. Front Endocrinol (Lausanne). 2018;9; 258. doi: 10.3389/fendo.2018.00258. The impact of exercise and fitness is so great that it does better than any drug treatment. In a study assessing the association of mortality (death) with cardiorespiratory fitness in patients undergoing exercise testing, the investigators found that with increased fitness, all-cause mortality went lower and lower. Comparing the risk increase of someone in the low fitness group (1st quartile) vs. the above average fitness group (3rd quartile), the low fitness group had a 2.75x increase in mortality compared to the above average fitness group. The impact of being in the least fit 25% is equivalent to the risk of dying from end-stage renal disease and greater than the risk associated with smoking. Being fit matters!

Fitness mitigates the age-related decline of cardiovascular, respiratory, musculoskeletal systems. Resistance training helps to limit bone and muscle mass loss.⁵⁰Lee S, Kim JS, Park KS, Baek KW, Yoo JI. Daily Walking Accompanied with Intermittent Resistance Exercise Prevents Osteosarcopenia: A Large Cohort Study. J Bone Metab. 2022 Nov;29(4):255-263. doi: 10.11005/jbm.2022.29.4.255 Moderate exercise may also help mitigate the deterioration of the immune system.

Drugs to slow aging: The Interventions Testing Program (ITP)

The National Institute on Aging (NIA) sponsors the “Interventions Testing Program (ITP)“, to evaluate drugs or nutriceuticals (any substance that is a food or part of a food) that might slow aging and extend a healthy lifespan in mice.

The ITP is important because the NIA is an independent research body and tests are conducted at three research sites simultaneously on male and female genetically heterogeneous UM-HET3 mice. The ITP receives proposals for substances to be tested from the research community, and up to six agents are accepted for testing each year.

What has the ITP found so far?

All compounds tested by the ITP and those that are in progress are listed on the ITP website.

To date, six compounds have shown significant extension of lifespan in mice:⁵¹Nadon NL, Strong R, Miller RA, Harrison DE. NIA Interventions Testing Program: Investigating Putative Aging Intervention Agents in a Genetically Heterogeneous Mouse Model. EBioMedicine. 2017;21; 3-4. doi: 10.1016/j.ebiom.2016.11.038

• Aspirin – males only.
• Rapamycin – males and females.
• 17α Estradiol – males only.
• Acarbose – males and females.
• Nordihydroguaiaretic acid (NDGA) – males only.
• Protandim® a blend of five herbal ingredients: (Milk thistle (Silybum marianum), Bacopa (Bacopa monnieri) extract, Ashwagandha (Withania somnifera) powder, green tea (Camellia sinensis) extract, and Turmeric (Curcuma longa) extract – males only.

Should I be taking these medications to slow aging?

The ITP conducts excellent research on mice. However, before a medication can be accepted for widespread use in humans, it must undergo rigorous testing for safety and efficacy in humans.

What about diet?

There are endless fad diets and individuals promoting one diet above another, making it hard to decipher fact from fiction. Nutrition research is very difficult to conduct and interpret. There are many variables that can be difficult to control, such as the wide variability of nutrients in foods and dietary patterns, food environment, approaches used to collect and analyse dietary data, and the manner in which results are reported. As an example, the food frequency questionnaire is a widely used tool to assess individuals’ dietary patterns. Most people find it hard to remember exactly what foods/quantities they have eaten, resulting in recall bias, which is a major problem of this tool.

With regard to diet, there are some irrefutable ground truths. Humans need essential vitamins, trace elements, essential amino acids, and fatty acids. A deficiency in any one of these will result in a disease.

Body weight

Apart from the ground truths above, it is important to be of a healthy body weight as being either overweight or underweight creates problems with metabolic health. Body mass index is an old and often inaccurate measure of health.⁵²Romero-Corral A, Somers VK, Sierra-Johnson J, Thomas RJ, Collazo-Clavell ML, Korinek J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond). 2008;32; 959-966. doi: 10.1038/ijo.2008.11. A whole body DEXA scan is a much more accurate way of measuring body composition, and in particular, visceral body fat,⁵³Naboush A, Hamdy O. Measuring visceral and hepatic fat in clinical practice and clinical research. Endocr Pract. 2013;19; 587-589. doi: 10.4158/EP12331.OR. which is associated with metabolic disease and cardiovascular disease.⁵⁴Despres JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012;126; 1301-1313. doi: 10.1161/CIRCULATIONAHA.111.067264.^,55Neeland IJ, Turer AT, Ayers CR, Powell-Wiley TM, Vega GL, Farzaneh-Far R, et al. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA. 2012;308; 1150-1159. doi: 10.1001/2012.jama.11132.

Fibre intake

Ensuring adequate intake of fibre is beneficial not only for the gut’s microbiome,⁵⁶O’Keefe SJ. The association between dietary fibre deficiency and high-income lifestyle-associated diseases: Burkitt’s hypothesis revisited. Lancet Gastroenterol Hepatol. 2019;4; 984-996. doi: 10.1016/S2468-1253(19)30257-2. but also for all-cause and cardiovascular-related mortality, incidence of coronary heart disease, stroke incidence, type 2 diabetes, and colorectal cancer.⁵⁷Reynolds A, Mann J, Cummings J, Winter N, Mete E, Te Morenga L. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Lancet. 2019;393; 434-445. doi: 10.1016/S0140-6736(18)31809-9. A risk reduction occurred at a daily fibre intake of 25-29 g but there does not appear to be a ceiling effect; the higher the fibre intake, the greater the risk reduction.⁵⁸Reynolds A, Mann J, Cummings J, Winter N, Mete E, Te Morenga L. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. Lancet. 2019;393; 434-445. doi: 10.1016/S0140-6736(18)31809-9.

What about caloric restriction?

Caloric restriction (CR) refers to a reduction in total calories consumed over day(s). It does not matter when the food was consumed or how often the food was consumed – only the total over a day matters. It is distinct from time-restricted feeding (TRF) which means either skipping a meal or eating within a certain timeframe. Intermittent fasting (IF) refers to a complete absence of food consumption for 24 hours or more. These terms are often used interchangeably, but they mean very different things.

Caloric restriction has been shown to extend life span and retard age-related chronic diseases in a variety of species, including rats, mice, fish, flies, worms, and yeast. Its main mechanism is thought to be that it induces repair and recycling pathways, including autophagy, mitophagy, DNA repair, and oxidant defence.⁵⁹Green CL, Lamming DW, Fontana L. Molecular mechanisms of dietary restriction promoting health and longevity. Nat Rev Mol Cell Biol. 2022;23; 56-73. doi: 10.1038/s41580-021-00411-4.

However, scrutiny of the research shows that the increase in longevity is not universal and may not even be shared among different strains of the same species. A flaw in the studies on mice was that the control group were allowed to eat as much as possible, became overweight, and were prone to early onset of diseases and death. Furthermore, results were not consistent across different genotypes of mice.⁶⁰Sohal RS, Forster MJ. Caloric restriction and the aging process: a critique. Free Radic Biol Med. 2014;73; 366-382. doi: 10.1016/j.freeradbiomed.2014.05.015.

Caloric restriction carries a risk of malnutrition and sarcopenia (loss of muscle mass). Sarcopenia in itself carries a risk of mortality.⁶¹Xu J, Wan CS, Ktoris K, Reijnierse EM, Maier AB. Sarcopenia Is Associated with Mortality in Adults: A Systematic Review and Meta-Analysis. Gerontology. 2022;68; 361-376. doi: 10.1159/000517099.

How is prevention of aging relevant to skin cancer?

Dermatologists often recommend UV-protection as the main means of skin cancer prevention. However, numerous epidemiological studies have shown that older age is the greatest risk factor for skin cancers.⁶²Garcovich S, Colloca G, Sollena P, Andrea B, Balducci L, Cho WC, et al. Skin Cancer Epidemics in the Elderly as An Emerging Issue in Geriatric Oncology. Aging Dis. 2017;8; 643-661. doi:10.14336/AD.2017.0503. Whilst a possible explanation is cumulative sun-exposure (the older one is, the more sun-damaged one gets), aging per se is a risk factor for all cancer types.⁶³National Cancer Institute. Age and Cancer Risk. at www.cancer.gov (2021). (Accessed April 2024.) This is because repair mechanisms in the body are less effective as we age explaining the substantial overlap between the hallmarks of aging and the hallmarks of cancer. It is possible that if aging could be managed or slowed-down that we would be able to reduce the risk of skin cancers too.

Strategies to reduce the appearance of aging

At all ages, the most effective treatment is sun protection. Strategies for sun protection are discussed in detail at our sister clinic, Skintel. This can help slow the development of wrinkles and preserve collagen and elastin in the skin.

New Zealand’s sun is one of the most intense in the world. Combining this fact with our love of the outdoors can lead to premature aging. Some studies have shown that people who live in Northern European regions with less lifetime sun exposure can look as much as 15 years younger, compared to people who have primarily lived in New Zealand.

Avoiding other notorious lifestyle habits can help including smoking, vaping, nicotine, and alcohol.

Topical tretinoin has been proven to reverse many changes of aging in the skin.⁶⁴Griffiths CE. The role of retinoids in the prevention and repair of aged and photoaged skin. Clin Exp Dermatol. 2001;26(7):613-618. doi:10.1046/j.1365-2230.2001.00892.x

Strategies and treatments that can be undertaken by decade

The twenties

Botox and fillers are becoming more commonly used within this age group as more evidence accumulates about their ability to maintain youthful-looking skin at its best. Studies have shown that Botox slows aging.

Scars acquired during childhood and teenage years, particularly from acne, can have a significant impact on the appearance of age. Texture from less severe acne and childhood sun exposure can also be improved.

The thirties

Early signs of aging are almost certainly appearing in those who have spent most of their lives in New Zealand.

Botox is very commonly requested to settle lines and wrinkles which can help reverse and slow the signs of aging with minimal downtime. Fillers are also very popular in this age to treat volume loss which often becomes noticeable. Laser treatments and other energy devices can help improve the texture and tone of the skin.

Pigmentation is also a common complaint, either from pregnancy or from early photoaging. We have several treatments that are commonly used to help with this.

For women who have completed their families, these treatments are often included as part of a ‘mummy makeover‘.

The fourties and on

Signs of aging are typically well established, such as lines, wrinkles, and volume loss. Other common concerns at this age are pigmentation, vascular (red) spots, and a mottled skin texture.

The use of Botox and dermal fillers continues to be increasingly common at this age due to their cost-effectiveness and minimal downtime.

Lasers become more commonly used as well for pigmentation (brown) spots and vascular (red) areas. Lasers and other energy-based devices are also commonly used for resurfacing and skin tightening.

Pre-cancerous spots commonly start to accumulate and can be treated with anti-cancer creams before they develop into proper skin cancers. These treatments can also have a small rejuvenation effect.

Summary

The science of aging is rapidly advancing. While there is no magic pill currently, there are a multitude of factors that can help.

The three most important pillars of healthy living are:

• Exercise
• Maintaining a healthy diet (rich in plants and high in fibre)
• Maintaining a healthy body composition

There is interesting research on the horizon, for example, a recently discovered drug has been shown to have the same effect as exercise.⁶⁵Billon C, Schoepke E, Avdagic A, Chatterjee A, Butler AA, Elgendy B, et al. A Synthetic ERR Agonist Alleviates Metabolic Syndrome. J Pharmacol Exp Ther. 2024;388; 232-240. doi: 10.1124/jpet.123.001733.

This page will be updated as new ground-breaking research is published.