Dr Ray O’Connor takes a look at the latest clinical papers on lifestyle, taking a look at longevity and socioeconomic disadvantage, and physical activity and ageing
Physical Activity and Ageing
Physical activity reduces the risk of mortality and age-related chronic diseases, yet its association with biological age measured by DNA methylation (DNAm) clocks remains unclear. This systematic review and meta-analysis1 aimed to evaluate the association between physical activity and biological age measured by DNAm clocks.
The authors conducted a systematic search of Embase, Cochrane Central Register of Controlled Trials, PubMed, Ovid, Scopus, and Web of Science from Jan 1, 2011, to June 6, 2025, to identify articles on the associations of physical activity and DNAm age, epigenetic age acceleration (EAA), or epigenetic age deviation in humans. Studies were included if they were peer-reviewed, published in English, included a study population with a mean or median age of 18 years or older, and investigated the association between DNAm clocks and physical activity in humans.
Dr Ray O’Connor
The authors also conducted a publication bias analysis and influence analysis. 34,437 articles were identified, and after removal of duplicates and screening, 44 studies were included in the systematic review comprising 145,465 participants: 62,887 (43⋅2 per cent) females and 82,578 (56⋅8 per cent) males, with mean ages ranging from 24⋅1 years to 78⋅5 years. Across studies, higher levels of physical activity were generally associated with lower DNAm age, although many individual associations did not reach statistical significance.
Seven cross-sectional studies contributed to the meta-analysis. The authors concluded that higher physical activity is significantly associated with lower biological age. However, evidence is predominantly from cross-sectional studies, limiting causal inference. The authors recommend that longitudinal studies and clinical trials using standardised, objectively measured physical activity are warranted to clarify dose–response relationships, and to determine whether physical activity can causally modify ageing trajectories, thereby informing precision strategies for healthy longevity.
New Onset Walking Limitations and associated morbidity and mortality
Life expectancy is increasing globally, but if people are to age healthily, they must do so with fewer limitations in their daily activities. However, information on either the frequency or risk factors for limitations to walking ability or other key activities across different regions of the world is limited. The aim of the PURE study2 was to describe the incidence, trajectories, risk factors, and population-attributable fraction of new-onset walking limitations in 25 countries at all socioeconomic levels.
PURE is an ongoing, prospective cohort study. The current analysis included community-dwelling participants who lived in four high-income countries (HICs), 16 middle-income countries (MICs), and five low-income countries (LICs). Individuals aged 35–70 years at baseline who completed a baseline questionnaire about activity limitations between Jan 12, 2001, and May 6, 2019, were included in the analysis. The activity limitation screen included questions on self-reported difficulty with walking, grasping, bending, seeing close-up, seeing distance, and hearing.
The primary outcome was incident walking limitation and the analytic sample comprised those with no walking limitation at baseline. The authors estimated the incidence rates, adjusted for age and sex, per 100 person-years in the overall PURE population, by country income level (and separately for China) and sex. They used multistate modelling to evaluate trajectories across the life course, analysed across continuous age, through three distinct sequential states: no limitation, walking limitation, and death. They used survival models to evaluate the associations of socioeconomic status, vascular and behavioural factors, community walkability, and incident adverse events, with incident walking limitations.
They then calculated the population-attributable fraction of selected modifiable factors and compared the risk factors for walking limitation and mortality. The results were as follows. Some 172,889 people from the PURE cohort answered questions on walking limitations at baseline, 150,221 of whom reported no walking limitation and were included in the multistate model. Of these 150,221 individuals, 122,538 had at least one follow-up assessment with walking limitations data (mean age at baseline 49⋅7 years; 71,424 [58⋅3 per cent] female and 51,114 [41⋅7 per cent] male). Mean follow-up was 14⋅5 years. Incidence of a new walking limitation per 100 person-years was higher in LICs (3⋅34), and lowest in China (0⋅58), compared with other MICs (1⋅80) and HICs (1⋅31). The incidence of walking limitation was higher in female participants (1⋅84) than in male participants (1⋅25).
In multistate models, state transitions from no walking limitation to walking limitation and death occurred at a higher rate and earlier in LICs, where the age at which the probability of transitioning to a walking limitation was reached by an estimated one-third of people at 64 years compared with age 76 years in HICs. Female participants had a higher probability of incident walking limitation across the age spectrum compared with male participants.
Many socioeconomic, vascular, and behavioural risk factors, community walkability, and incident adverse events, especially incident stroke, were associated with incident walking limitations. The population-level risk factors with the highest population attributable fractions for walking limitation were low education (11⋅1 per cent), obesity (5⋅2 per cent), hypertension (3⋅6 per cent), and low recreational physical activity (4⋅3 per cent), with obesity being the highest in HICs (12⋅9 per cent) and low education being the highest elsewhere. Potentially modifiable individual-level risk factors explained approximately 32⋅9 per cent of the population’s risk of walking limitations and approximately 47⋅4 per cent of mortality, and four of the top five factors were shared for both outcomes (low education, low recreational activity, poor diet, and hypertension).
The authors concluded that individuals in LICs had an accelerated transition to walking limitation, which was approximately 12 years earlier than those in HICs. Walking limitation and mortality shared a common set of modifiable risk factors accounting for almost one-third of the population-level risk of walking limitations and highlighting opportunities for integrated prevention strategies in mid-life that simultaneously target disability and premature mortality across socioeconomic settings.
Socioeconomic Disadvantage and Self-Reported Health
Good health is a critical asset for society, underlying the ability to work, lead fulfilling lives and participate in family and community life. Yet the United Kingdom (UK) faces a growing challenge: life expectancy improvements have stalled, health inequalities are widening and working-age health has deteriorated significantly compared with peer countries. It is well understood that population health generally deteriorates with age.
But this tends to happen faster for people who experience socioeconomic disadvantage over their lifetimes. The novel analysis in this population study3 links the latest census data from 2021 with that from 2011, allowing the authors to study how people’s health changed over the decade. The analysis was underpinned by modelling from the Office for National Statistics, was the largest study of its kind. The summary points of the report are as follows.
The UK faces a growing working-age health challenge and widening health inequalities. The authors found where people live affected the rate of decline in good health. One in five people (18 people) of working age who lived in the most deprived areas, no longer reported good health a decade later (compared with 13 per cent overall).
Working-age people (16–69 years) living in the most deprived areas faced an at least 43 per cent higher risk of no longer reporting good health, compared with those in the least deprived areas after accounting for demographic and socioeconomic differences.
Females aged 20–24 years in the most deprived areas in 2011 had a 72 per cent higher risk of no longer reporting good health a decade later compared with those in the least deprived areas (70 per cent higher for males).
The analysis shows the main socioeconomic factors linked to people no longer reporting good health are unemployment, being economically inactive and living in the private or social-rented sector. These factors are also associated with reduced likelihood of returning to good health.
For example, people who were unemployed but looking for work in 2011 had a 67 per cent (female) and 82 per cent (male) higher likelihood of no longer being in good health a decade later, compared with their peers in employment. This analysis adds to evidence on the need for a preventative approach that helps keep people healthy, so they can fulfill their individual and economic potential. Policy action should focus on preventing people from leaving the labour market and on improving housing quality and security.
Hereditability of Human Lifespan
How heritable is human life span? If genetic heritability is high, longevity genes can reveal aging mechanisms and inform medicine and public health. However, current estimates of heritability are low—twin studies show heritability of only 20 to 25 per cent, and recent large pedigree studies suggest it is as low as six per cent. The authors of this study4 used model-independent mathematical analysis and simulations of two human mortality models to partition mortality into intrinsic and extrinsic components.
They tested their conclusions on data from three different twin studies, including the SATSA (Swedish Adoption/Twin Study of Aging) study, containing data from twins raised apart that have not been previously analysed for life-span heritability. The authors postulate that mortality estimates are often confounded by extrinsic mortality—deaths caused by extrinsic factors such as accidents or infections. They conclude that their use of mathematical modelling and analyses of twin cohorts raised together and apart corrected for this factor, reveal that heritability of human life span due to intrinsic mortality is above 50 per cent. Such high heritability is similar to that of most other complex human traits and to life-span heritability in other species. 
References:
Shan J et al. Physical activity and biological age measured by DNA methylation clocks: a systematic review and meta-analysis. Lancet Healthy Longev 2026; 7: 100835. Published Online April 29, 2026. https://doi.org/10.1016/j.lanhl.2026.100835
Joundi R et al. Life-course trajectories and modifiable risk factors for incident walking limitation and mortality in 25 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet Healthy Longev 2026; 7: 100837. Published Online May 11, 2026. https://doi.org/10.1016/j.lanhl.2026.100837
Health Foundation. Socioeconomic disadvantage and self-reported health. 2026. health.org.uk/reports-and-analysis/analysis/socioeconomic-disadvantage-and-self-reportedhealth
Shenhar B et al. Heritability of intrinsic human life span is about 50% when confounding factors are addressed. Science 29 Jan 2026 Vol 391, Issue 6784 pp. 504-510. https://doi.org/10.1126/science.adz1187